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199 results on '"Männistö, Satu"'

1. Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author: Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E.W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun Seog, Shin, Min Ho, Shin, Aesun, Ahn, Yoon Ok, Kim, Dong Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu Tang, Jia, Wei Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D.P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J.M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, Zheng, Wei, Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E.W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun Seog, Shin, Min Ho, Shin, Aesun, Ahn, Yoon Ok, Kim, Dong Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu Tang, Jia, Wei Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D.P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J.M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei
Abstract: Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
Published: 2024

2. Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author: Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, Zheng, Wei, Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei
Abstract: Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
Published: 2024
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3. Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author: Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, Zheng, Wei, Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei
Abstract: Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
Published: 2024
Full Text: View/download PDF

4. Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Author: Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, Zheng, Wei, Chen, Zhishan, Guo, Xingyi, Tao, Ran, Huyghe, Jeroen R., Law, Philip J., Fernandez-Rozadilla, Ceres, Ping, Jie, Jia, Guochong, Long, Jirong, Li, Chao, Shen, Quanhu, Xie, Yuhan, Timofeeva, Maria N., Thomas, Minta, Schmit, Stephanie L., Díez-Obrero, Virginia, Devall, Matthew, Moratalla-Navarro, Ferran, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah E. W., Svinti, Victoria, Donnelly, Kevin, Farrington, Susan M., Blackmur, James, Vaughan-Shaw, Peter G., Shu, Xiao-Ou, Lu, Yingchang, Broderick, Peter, Studd, James, Harrison, Tabitha A., Conti, David V., Schumacher, Fredrick R., Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John L., Jenkins, Mark A., Win, Aung Ko, Pai, Rish K., Figueiredo, Jane C., Haile, Robert W., Gallinger, Steven, Woods, Michael O., Newcomb, Polly A., Duggan, David, Cheadle, Jeremy P., Kaplan, Richard, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Jukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri A., Rissanen, Harri, Pukkala, Eero, Eriksson, Johan G., Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie J., Ruiz-Narvaez, Edward, Palmer, Julie R., Buchanan, Daniel D., Platz, Elizabeth A., Visvanathan, Kala, Ulrich, Cornelia M., Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter T., Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha L., Potter, John D., Tsilidis, Kostas K., Schulze, Matthias B., Gunter, Marc J., Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Bishop, D. Timothy, Giles, Graham G., Southey, Melissa C., Idos, Gregory E., McDonnell, Kevin J., Abu-Ful, Zomoroda, Greenson, Joel K., Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope O., van Guelpen, Bethany, Hudson, Thomas J., Hampel, Heather, Pearlman, Rachel, Berndt, Sonja I., Hayes, Richard B., Martinez, Marie Elena, Thomas, Sushma S., Pharoah, Paul D. P., Larsson, Susanna C., Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly F., Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew T., Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David J., Joshi, Amit D., Schafmayer, Clemens, Scacheri, Peter C., Kundaje, Anshul, Schoen, Robert E., Hampe, Jochen, Stadler, Zsofia K., Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Edlund, Christopher K., Gauderman, W. James, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen J., van Duijnhoven, Franzel, Feskens, Edith J. M., Sakoda, Lori C., Gago-Dominguez, Manuela, Wolk, Alicja, Pardini, Barbara, FitzGerald, Liesel M., Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie A., Kooperberg, Charles, Li, Christopher I., Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Le Marchand, Loic, Wu, Anna H., Qu, Chenxu, McNeil, Caroline E., Coetzee, Gerhard, Hayward, Caroline, Deary, Ian J., Harris, Sarah E., Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Lau, Ken S., Zhao, Hongyu, Hsu, Li, Cai, Qiuyin, Dunlop, Malcolm G., Gruber, Stephen B., Houlston, Richard S., Moreno, Victor, Casey, Graham, Peters, Ulrike, Tomlinson, Ian, and Zheng, Wei
Abstract: Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
Published: 2024
Full Text: View/download PDF

5. Genome-wide interaction analysis of folate for colorectal cancer risk

Author: Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, and Tsilidis, Konstantinos K.
Abstract: Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions: Variation in 3p25.2 locus may modify the
Published: 2023
Full Text: View/download PDF

6. Genome-wide interaction analysis of folate for colorectal cancer risk

Author: Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, and Tsilidis, Konstantinos K.
Abstract: Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions: Variation in 3p25.2 locus may modify the
Published: 2023
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7. Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author: Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao-ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, Peters, Ulrike, Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao-ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun-Seog, Shin, Min-Ho, Shin, Aesun, Ahn, Yoon-Ok, Kim, Dong-Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu-Tang, Jia, Wei-Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka-Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu-Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz-Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, and Peters, Ulrike
Abstract: Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies., Errata: Fernandez-Rozadilla, C., Timofeeva, M., Chen, Z. et al. Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries. Nat Genet (2023). DOI: 10.1038/s41588-023-01334-w
Published: 2023
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8. Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise. Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before
Published: 2023
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9. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., and The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS
Abstract: Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Published: 2023
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10. Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level : findings from the MORGAM project

Author: Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, McElduff, Patrick, Linneberg, Allen, Salomaa, Veikko, Männistö, Satu, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Tamosiunas, Abdonas, Grimsgaard, Sameline, Drygas, Wojciech, Malyutina, Sofia, Söderberg, Stefan, Nordendahl, Maria, Kee, Frank, Grassi, Guido, Dabboura, Salim, Borchini, Rossana, Westermann, Dirk, Schrage, Benedikt, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, Iacoviello, Licia, de Gaetano, Giovanni, Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, McElduff, Patrick, Linneberg, Allen, Salomaa, Veikko, Männistö, Satu, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Tamosiunas, Abdonas, Grimsgaard, Sameline, Drygas, Wojciech, Malyutina, Sofia, Söderberg, Stefan, Nordendahl, Maria, Kee, Frank, Grassi, Guido, Dabboura, Salim, Borchini, Rossana, Westermann, Dirk, Schrage, Benedikt, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, Iacoviello, Licia, and de Gaetano, Giovanni
Abstract: The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1–10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74–1.02), 11% (HR = 0.89; 0.84–0.95) and 5% (HR = 0.95; 0.89–1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82–1.25), 10% (HR = 1.10; 1.02–1.19) and 17% (HR = 1.17; 1.09–1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.
Published: 2023
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11. Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise. Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before
Published: 2023
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12. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., and The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS
Abstract: Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Published: 2023
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13. Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise. Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before
Published: 2023
Full Text: View/download PDF

14. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., and The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS
Abstract: Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Published: 2023
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15. Genome-wide interaction analysis of folate for colorectal cancer risk.

Author: Bouras, Emmanouil, Bouras, Emmanouil, Kim, Andre, Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth, Baurley, James, Berndt, Sonja, Bien, Stephanie, Bishop, Timothy, Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter, Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng, Chan, Andrew, Chang-Claude, Jenny, Conti, David, Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David, Figueiredo, Jane, Giles, Graham, Gruber, Stephen, Gunter, Marc, Harrison, Tabitha, Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen, Joshi, Amit, Kawaguchi, Eric, Keku, Temitope, Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan, Li, Li, Lynch, Brigid, Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly, Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie, Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew, Peoples, Anita, Platz, Elizabeth, Potter, John, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori, Schmit, Stephanie, Shcherbina, Anna, Stern, Mariana, Su, Yu-Ru, Tangen, Catherine, Thomas, Duncan, Tian, Yu, Um, Caroline, van Duijnhoven, Franzel, Van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael, Ulrich, Cornelia, Hsu, Li, Gauderman, W, Peters, Ulrike, Tsilidis, Konstantinos, Qi, Lihong, Bouras, Emmanouil, Bouras, Emmanouil, Kim, Andre, Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth, Baurley, James, Berndt, Sonja, Bien, Stephanie, Bishop, Timothy, Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter, Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng, Chan, Andrew, Chang-Claude, Jenny, Conti, David, Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David, Figueiredo, Jane, Giles, Graham, Gruber, Stephen, Gunter, Marc, Harrison, Tabitha, Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen, Joshi, Amit, Kawaguchi, Eric, Keku, Temitope, Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan, Li, Li, Lynch, Brigid, Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly, Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie, Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew, Peoples, Anita, Platz, Elizabeth, Potter, John, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori, Schmit, Stephanie, Shcherbina, Anna, Stern, Mariana, Su, Yu-Ru, Tangen, Catherine, Thomas, Duncan, Tian, Yu, Um, Caroline, van Duijnhoven, Franzel, Van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael, Ulrich, Cornelia, Hsu, Li, Gauderman, W, Peters, Ulrike, Tsilidis, Konstantinos, and Qi, Lihong
Abstract: BACKGROUND: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folates role in CRC. OBJECTIVES: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. METHODS: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). RESULTS: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. CONCLUSIONS: Variation in 3p25.2 locus may modify the
Published: 2023

16. Genome-wide interaction analysis of folate for colorectal cancer risk

Author: Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, and Tsilidis, Konstantinos K.
Abstract: Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions: Variation in 3p25.2 locus may modify the
Published: 2023
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17. Genome-wide interaction analysis of folate for colorectal cancer risk

Author: Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, Tsilidis, Konstantinos K., Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu-Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel JB., van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, W James, Peters, Ulrike, and Tsilidis, Konstantinos K.
Abstract: Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions: Variation in 3p25.2 locus may modify the
Published: 2023
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18. Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level: findings from the MORGAM project

Author: Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Mcelduff, P, Linneberg, A, Salomaa, V, Männistö, S, Ferrières, J, Dallongeville, J, Thorand, B, Brenner, H, Ferrario, M, Veronesi, G, Tamosiunas, A, Grimsgaard, S, Drygas, W, Malyutina, S, Söderberg, S, Nordendahl, M, Kee, F, Grassi, G, Dabboura, S, Borchini, R, Westermann, D, Schrage, B, Zeller, T, Kuulasmaa, K, Blankenberg, S, Donati, M, Iacoviello, L, de Gaetano, G, Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, McElduff, Patrick, Linneberg, Allen, Salomaa, Veikko, Männistö, Satu, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Tamosiunas, Abdonas, Grimsgaard, Sameline, Drygas, Wojciech, Malyutina, Sofia, Söderberg, Stefan, Nordendahl, Maria, Kee, Frank, Grassi, Guido, Dabboura, Salim, Borchini, Rossana, Westermann, Dirk, Schrage, Benedikt, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, Iacoviello, Licia, de Gaetano, Giovanni, Di Castelnuovo, A, Bonaccio, M, Costanzo, S, Mcelduff, P, Linneberg, A, Salomaa, V, Männistö, S, Ferrières, J, Dallongeville, J, Thorand, B, Brenner, H, Ferrario, M, Veronesi, G, Tamosiunas, A, Grimsgaard, S, Drygas, W, Malyutina, S, Söderberg, S, Nordendahl, M, Kee, F, Grassi, G, Dabboura, S, Borchini, R, Westermann, D, Schrage, B, Zeller, T, Kuulasmaa, K, Blankenberg, S, Donati, M, Iacoviello, L, de Gaetano, G, Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, McElduff, Patrick, Linneberg, Allen, Salomaa, Veikko, Männistö, Satu, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Tamosiunas, Abdonas, Grimsgaard, Sameline, Drygas, Wojciech, Malyutina, Sofia, Söderberg, Stefan, Nordendahl, Maria, Kee, Frank, Grassi, Guido, Dabboura, Salim, Borchini, Rossana, Westermann, Dirk, Schrage, Benedikt, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, Iacoviello, Licia, and de Gaetano, Giovanni
Abstract: The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1–10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74–1.02), 11% (HR = 0.89; 0.84–0.95) and 5% (HR = 0.95; 0.89–1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82–1.25), 10% (HR = 1.10; 1.02–1.19) and 17% (HR = 1.17; 1.09–1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.
Published: 2023

19. Genome-wide interaction analysis of folate for colorectal cancer risk

Author: Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel, Van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, James, Peters, Ulrike, Tsilidis, Konstantinos K., Bouras, Emmanouil, Kim, Andre E., Lin, Yi, Morrison, John, Du, Mengmeng, Albanes, Demetrius, Barry, Elizabeth L., Baurley, James W., Berndt, Sonja I., Bien, Stephanie A., Bishop, Timothy D., Brenner, Hermann, Budiarto, Arif, Burnett-Hartman, Andrea, Campbell, Peter T., Carreras-Torres, Robert, Casey, Graham, Cenggoro, Tjeng Wawan, Chan, Andrew T., Chang-Claude, Jenny, Conti, David V., Cotterchio, Michelle, Devall, Matthew, Diez-Obrero, Virginia, Dimou, Niki, Drew, David A., Figueiredo, Jane C., Giles, Graham G., Gruber, Stephen B., Gunter, Marc J., Harrison, Tabitha A., Hidaka, Akihisa, Hoffmeister, Michael, Huyghe, Jeroen R., Joshi, Amit D., Kawaguchi, Eric S., Keku, Temitope O., Kundaje, Anshul, Le Marchand, Loic, Lewinger, Juan Pablo, Li, Li, Lynch, Brigid M., Mahesworo, Bharuno, Männistö, Satu, Moreno, Victor, Murphy, Neil, Newcomb, Polly A., Obón-Santacana, Mireia, Ose, Jennifer, Palmer, Julie R., Papadimitriou, Nikos, Pardamean, Bens, Pellatt, Andrew J., Peoples, Anita R., Platz, Elizabeth A., Potter, John D., Qi, Lihong, Qu, Conghui, Rennert, Gad, Ruiz-Narvaez, Edward, Sakoda, Lori C., Schmit, Stephanie L., Shcherbina, Anna, Stern, Mariana C., Su, Yu Ru, Tangen, Catherine M., Thomas, Duncan C., Tian, Yu, Um, Caroline Y., van Duijnhoven, Franzel, Van Guelpen, Bethany, Visvanathan, Kala, Wang, Jun, White, Emily, Wolk, Alicja, Woods, Michael O., Ulrich, Cornelia M., Hsu, Li, Gauderman, James, Peters, Ulrike, and Tsilidis, Konstantinos K.
Abstract: Background: Epidemiological and experimental evidence suggests that higher folate intake is associated with decreased colorectal cancer (CRC) risk; however, the mechanisms underlying this relationship are not fully understood. Genetic variation that may have a direct or indirect impact on folate metabolism can provide insights into folate's role in CRC. Objectives: Our aim was to perform a genome-wide interaction analysis to identify genetic variants that may modify the association of folate on CRC risk. Methods: We applied traditional case-control logistic regression, joint 3-degree of freedom, and a 2-step weighted hypothesis approach to test the interactions of common variants (allele frequency >1%) across the genome and dietary folate, folic acid supplement use, and total folate in relation to risk of CRC in 30,550 cases and 42,336 controls from 51 studies from 3 genetic consortia (CCFR, CORECT, GECCO). Results: Inverse associations of dietary, total folate, and folic acid supplement with CRC were found (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.90, 0.96; and 0.91; 95% CI: 0.89, 0.94 per quartile higher intake, and 0.82 (95% CI: 0.78, 0.88) for users compared with nonusers, respectively). Interactions (P-interaction < 5×10-8) of folic acid supplement and variants in the 3p25.2 locus (in the region of Synapsin II [SYN2]/tissue inhibitor of metalloproteinase 4 [TIMP4]) were found using traditional interaction analysis, with variant rs150924902 (located upstream to SYN2) showing the strongest interaction. In stratified analyses by rs150924902 genotypes, folate supplementation was associated with decreased CRC risk among those carrying the TT genotype (OR: 0.82; 95% CI: 0.79, 0.86) but increased CRC risk among those carrying the TA genotype (OR: 1.63; 95% CI: 1.29, 2.05), suggesting a qualitative interaction (P-interaction = 1.4×10-8). No interactions were observed for dietary and total folate. Conclusions: Variation in 3p25.2 locus may modify the assoc
Published: 2023

20. Exposure to long-term source-specific transportation noise and incident breast cancer:A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D, Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J, Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K, Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H, Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D, Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J, Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K, Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H, Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: BACKGROUND: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence.METHODS: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution.RESULTS: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th-95th percentile) 5-year residential road traffic noise was 54.8 (40.0-67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2-65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99-1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96-1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM 2.5 and attenuated when adjusted for NO 2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99-1.18) for road traffic and 1.19 (0.95-1.49) for railway noise. CONCLUSIONS: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway a
Published: 2023

21. Author Correction : Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

Author: Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao Ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun Seog, Shin, Min Ho, Shin, Aesun, Ahn, Yoon Ok, Kim, Dong Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu Tang, Jia, Wei Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, Peters, Ulrike, Fernandez-Rozadilla, Ceres, Timofeeva, Maria, Chen, Zhishan, Law, Philip, Thomas, Minta, Schmit, Stephanie, Díez-Obrero, Virginia, Hsu, Li, Fernandez-Tajes, Juan, Palles, Claire, Sherwood, Kitty, Briggs, Sarah, Svinti, Victoria, Donnelly, Kevin, Farrington, Susan, Blackmur, James, Vaughan-Shaw, Peter, Shu, Xiao Ou, Long, Jirong, Cai, Qiuyin, Guo, Xingyi, Lu, Yingchang, Broderick, Peter, Studd, James, Huyghe, Jeroen, Harrison, Tabitha, Conti, David, Dampier, Christopher, Devall, Mathew, Schumacher, Fredrick, Melas, Marilena, Rennert, Gad, Obón-Santacana, Mireia, Martín-Sánchez, Vicente, Moratalla-Navarro, Ferran, Oh, Jae Hwan, Kim, Jeongseon, Jee, Sun Ha, Jung, Keum Ji, Kweon, Sun Seog, Shin, Min Ho, Shin, Aesun, Ahn, Yoon Ok, Kim, Dong Hyun, Oze, Isao, Wen, Wanqing, Matsuo, Keitaro, Matsuda, Koichi, Tanikawa, Chizu, Ren, Zefang, Gao, Yu Tang, Jia, Wei Hua, Hopper, John, Jenkins, Mark, Win, Aung Ko, Pai, Rish, Figueiredo, Jane, Haile, Robert, Gallinger, Steven, Woods, Michael, Newcomb, Polly, Duggan, David, Cheadle, Jeremy, Kaplan, Richard, Maughan, Timothy, Kerr, Rachel, Kerr, David, Kirac, Iva, Böhm, Jan, Mecklin, Lukka Pekka, Jousilahti, Pekka, Knekt, Paul, Aaltonen, Lauri, Rissanen, Harri, Pukkala, Eero, Eriksson, Johan, Cajuso, Tatiana, Hänninen, Ulrika, Kondelin, Johanna, Palin, Kimmo, Tanskanen, Tomas, Renkonen-Sinisalo, Laura, Zanke, Brent, Männistö, Satu, Albanes, Demetrius, Weinstein, Stephanie, Ruiz-Narvaez, Edward, Palmer, Julie, Buchanan, Daniel, Platz, Elizabeth, Visvanathan, Kala, Ulrich, Cornelia, Siegel, Erin, Brezina, Stefanie, Gsur, Andrea, Campbell, Peter, Chang-Claude, Jenny, Hoffmeister, Michael, Brenner, Hermann, Slattery, Martha, Potter, John, Tsilidis, Konstantinos, Schulze, Matthias, Gunter, Marc, Murphy, Neil, Castells, Antoni, Castellví-Bel, Sergi, Moreira, Leticia, Arndt, Volker, Shcherbina, Anna, Stern, Mariana, Pardamean, Bens, Bishop, Timothy, Giles, Graham, Southey, Melissa, Idos, Gregory, McDonnell, Kevin, Abu-Ful, Zomoroda, Greenson, Joel, Shulman, Katerina, Lejbkowicz, Flavio, Offit, Kenneth, Su, Yu Ru, Steinfelder, Robert, Keku, Temitope, van Guelpen, Bethany, Hudson, Thomas, Hampel, Heather, Pearlman, Rachel, Berndt, Sonja, Hayes, Richard, Martinez, Marie Elena, Thomas, Sushma, Corley, Douglas, Pharoah, Paul, Larsson, Susanna, Yen, Yun, Lenz, Heinz Josef, White, Emily, Li, Li, Doheny, Kimberly, Pugh, Elizabeth, Shelford, Tameka, Chan, Andrew, Cruz-Correa, Marcia, Lindblom, Annika, Hunter, David, Joshi, Amit, Schafmayer, Clemens, Scacheri, Peter, Kundaje, Anshul, Nickerson, Deborah, Schoen, Robert, Hampe, Jochen, Stadler, Zsofia, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Papadopoulos, Nickolas, Edlund, Chistopher, Gauderman, William, Thomas, Duncan, Shibata, David, Toland, Amanda, Markowitz, Sanford, Kim, Andre, Chanock, Stephen, van Duijnhoven, Franzel, Feskens, Edith, Sakoda, Lori, Gago-Dominguez, Manuela, Wolk, Alicja, Naccarati, Alessio, Pardini, Barbara, FitzGerald, Liesel, Lee, Soo Chin, Ogino, Shuji, Bien, Stephanie, Kooperberg, Charles, Li, Christopher, Lin, Yi, Prentice, Ross, Qu, Conghui, Bézieau, Stéphane, Tangen, Catherine, Mardis, Elaine, Yamaji, Taiki, Sawada, Norie, Iwasaki, Motoki, Haiman, Christopher, Le Marchand, Loic, Wu, Anna, Qu, Chenxu, McNeil, Caroline, Coetzee, Gerhard, Hayward, Caroline, Deary, Ian, Harris, Sarah, Theodoratou, Evropi, Reid, Stuart, Walker, Marion, Ooi, Li Yin, Moreno, Victor, Casey, Graham, Gruber, Stephen, Tomlinson, Ian, Zheng, Wei, Dunlop, Malcolm, Houlston, Richard, and Peters, Ulrike
Abstract: In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article.
Published: 2023

22. Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise. Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before
Published: 2023
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23. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., and The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS
Abstract: Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Published: 2023
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24. Exposure to long-term source-specific transportation noise and incident breast cancer : A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D., Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J., Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K., Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H., Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: Background: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence. Methods: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution. Results: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th–95th percentile) 5-year residential road traffic noise was 54.8 (40.0–67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2–65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99–1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96–1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM2.5 and attenuated when adjusted for NO2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99–1.18) for road traffic and 1.19 (0.95–1.49) for railway noise. Conclusions: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway and aircraft noise before
Published: 2023
Full Text: View/download PDF

25. Circulating insulin-like growth factors and risks of overall, aggressive and early-onset prostate cancer : a collaborative analysis of 20 prospective studies and Mendelian randomization analysis

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS, Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-De-Mesquita, H. Bas, Cohn, Barbara A., Deschasaux-Tanguy, Melanie, Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Haiman, Christopher A., Hankey, Graham J., Holly, Jeffrey M. P., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Kubo, Tatsuhiko, Le Marchand, Loic, Macinnis, Robert J., Männistö, Satu, Metter, E. Jeffrey, Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Pollak, Michael N., Roobol, Monique J., Schaefer, Catherine A., Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Touvier, Mathilde, Van Den Eeden, Stephen K., Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., and The PRACTICAL Consortium, CRUK, BPC3, CAPS, PEGASUS
Abstract: Background: Previous studies had limited power to assess the associations of circulating insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) with clinically relevant prostate cancer as a primary endpoint, and the association of genetically predicted IGF-I with aggressive prostate cancer is not known. We aimed to investigate the associations of IGF-I, IGF-II, IGFBP-1, IGFBP-2 and IGFBP-3 concentrations with overall, aggressive and early-onset prostate cancer. Methods: Prospective analysis of biomarkers using the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group dataset (up to 20 studies, 17 009 prostate cancer cases, including 2332 aggressive cases). Odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression. For IGF-I, two-sample Mendelian randomization (MR) analysis was undertaken using instruments identified using UK Biobank (158 444 men) and outcome data from PRACTICAL (up to 85 554 cases, including 15 167 aggressive cases). Additionally, we used colocalization to rule out confounding by linkage disequilibrium. Results: In observational analyses, IGF-I was positively associated with risks of overall (OR per 1 SD = 1.09: 95% CI 1.07, 1.11), aggressive (1.09: 1.03, 1.16) and possibly early-onset disease (1.11: 1.00, 1.24); associations were similar in MR analyses (OR per 1 SD = 1.07: 1.00, 1.15; 1.10: 1.01, 1.20; and 1.13; 0.98, 1.30, respectively). Colocalization also indicated a shared signal for IGF-I and prostate cancer (PP4: 99%). Men with higher IGF-II (1.06: 1.02, 1.11) and IGFBP-3 (1.08: 1.04, 1.11) had higher risks of overall prostate cancer, whereas higher IGFBP-1 was associated with a lower risk (0.95: 0.91, 0.99); these associations were attenuated following adjustment for IGF-I. Conclusions: These findings support the role of IGF-I in the development of prostate cancer, including for aggressive disease.
Published: 2023
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26. Drinking alcohol in moderation is associated with lower rate of all-cause mortality in individuals with higher rather than lower educational level:findings from the MORGAM project

Author: Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, McElduff, Patrick, Linneberg, Allen, Salomaa, Veikko, Männistö, Satu, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Tamosiunas, Abdonas, Grimsgaard, Sameline, Drygas, Wojciech, Malyutina, Sofia, Söderberg, Stefan, Nordendahl, Maria, Kee, Frank, Grassi, Guido, Dabboura, Salim, Borchini, Rossana, Westermann, Dirk, Schrage, Benedikt, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, Iacoviello, Licia, de Gaetano, Giovanni, Di Castelnuovo, Augusto, Bonaccio, Marialaura, Costanzo, Simona, McElduff, Patrick, Linneberg, Allen, Salomaa, Veikko, Männistö, Satu, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Tamosiunas, Abdonas, Grimsgaard, Sameline, Drygas, Wojciech, Malyutina, Sofia, Söderberg, Stefan, Nordendahl, Maria, Kee, Frank, Grassi, Guido, Dabboura, Salim, Borchini, Rossana, Westermann, Dirk, Schrage, Benedikt, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, Iacoviello, Licia, and de Gaetano, Giovanni
Abstract: The association between socioeconomic status (SES) and alcohol-related diseases has been widely explored. Less is known, however, on whether the association of moderate drinking with all-cause mortality is modified by educational level (EL). Using harmonized data from 16 cohorts in the MORGAM Project (N = 142,066) the association of pattern of alcohol intake with hazard of all-cause mortality across EL (lower = primary-school; middle = secondary-school; higher = university/college degree) was assessed using multivariable Cox-regression and spline curves. A total of 16,695 deaths occurred in 11.8 years (median). In comparison with life-long abstainers, participants drinking 0.1–10 g/d of ethanol had 13% (HR = 0.87; 95%CI: 0.74–1.02), 11% (HR = 0.89; 0.84–0.95) and 5% (HR = 0.95; 0.89–1.02) lower rate of death in higher, middle and lower EL, respectively. Conversely, drinkers > 20 g/d had 1% (HR = 1.01; 0.82–1.25), 10% (HR = 1.10; 1.02–1.19) and 17% (HR = 1.17; 1.09–1.26) higher rate of death. The association of alcohol consumption with all-cause mortality was nonlinear, with a different J-shape by EL levels. It was consistent across both sexes and in various approaches of measuring alcohol consumption, including combining quantity and frequency and it was more evident when the beverage of preference was wine. We observed that drinking in moderation (≤ 10 g/d) is associated with lower mortality rate more evidently in individuals with higher EL than in people with lower EL, while heavy drinking is associated with higher mortality rate more evidently in individuals with lower EL than in people with higher EL, suggesting that advice on reducing alcohol intake should especially target individuals of low EL.
Published: 2023

27. Exposure to long-term source-specific transportation noise and incident breast cancer:A pooled study of eight Nordic cohorts

Author: Thacher, Jesse D, Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J, Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K, Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H, Ögren, Mikael, Åkesson, Agneta, Sørensen, Mette, Thacher, Jesse D, Oudin, Anna, Flanagan, Erin, Mattisson, Kristoffer, Albin, Maria, Roswall, Nina, Pyko, Andrei, Aasvang, Gunn Marit, Andersen, Zorana J, Borgquist, Signe, Brandt, Jørgen, Broberg, Karin, Cole-Hunter, Thomas, Eriksson, Charlotta, Eneroth, Kristina, Gudjonsdottir, Hrafnhildur, Helte, Emilie, Ketzel, Matthias, Lanki, Timo, Lim, Youn-Hee, Leander, Karin, Ljungman, Petter, Manjer, Jonas, Männistö, Satu, Raaschou-Nielsen, Ole, Pershagen, Göran, Rizzuto, Debora, Sandsveden, Malte, Selander, Jenny, Simonsen, Mette K, Stucki, Lara, Spanne, Mårten, Stockfelt, Leo, Tjønneland, Anne, Yli-Tuomi, Tarja, Tiittanen, Pekka, Valencia, Victor H, Ögren, Mikael, Åkesson, Agneta, and Sørensen, Mette
Abstract: BACKGROUND: Environmental noise is an important environmental exposure that can affect health. An association between transportation noise and breast cancer incidence has been suggested, although current evidence is limited. We investigated the pooled association between long-term exposure to transportation noise and breast cancer incidence.METHODS: Pooled data from eight Nordic cohorts provided a study population of 111,492 women. Road, railway, and aircraft noise were modelled at residential addresses. Breast cancer incidence (all, estrogen receptor (ER) positive, and ER negative) was derived from cancer registries. Hazard ratios (HR) were estimated using Cox Proportional Hazards Models, adjusting main models for sociodemographic and lifestyle variables together with long-term exposure to air pollution.RESULTS: A total of 93,859 women were included in the analyses, of whom 5,875 developed breast cancer. The median (5th-95th percentile) 5-year residential road traffic noise was 54.8 (40.0-67.8) dB Lden, and among those exposed, the median railway noise was 51.0 (41.2-65.8) dB Lden. We observed a pooled HR for breast cancer (95 % confidence interval (CI)) of 1.03 (0.99-1.06) per 10 dB increase in 5-year mean exposure to road traffic noise, and 1.03 (95 % CI: 0.96-1.11) for railway noise, after adjustment for lifestyle and sociodemographic covariates. HRs remained unchanged in analyses with further adjustment for PM 2.5 and attenuated when adjusted for NO 2 (HRs from 1.02 to 1.01), in analyses using the same sample. For aircraft noise, no association was observed. The associations did not vary by ER status for any noise source. In analyses using <60 dB as a cutoff, we found HRs of 1.08 (0.99-1.18) for road traffic and 1.19 (0.95-1.49) for railway noise. CONCLUSIONS: We found weak associations between road and railway noise and breast cancer risk. More high-quality prospective studies are needed, particularly among those exposed to railway a
Published: 2023

28. Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., and Travis, Ruth C.
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
Published: 2022
Full Text: View/download PDF

29. Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., and Travis, Ruth C.
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
Published: 2022
Full Text: View/download PDF

30. Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., and Travis, Ruth C.
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
Published: 2022
Full Text: View/download PDF

31. Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium

Author: Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, Söderberg, Stefan, Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, and Söderberg, Stefan
Abstract: Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25[OH]D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in 6 European countries by using harmonized immunoassay data from 81,084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48.9%; median age 50.8 years; examination period 1984 to 2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling, and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65.6 to 63.8 oN), Germany (at 48.4 oN), Finland (at 65.0 to 60.2 oN), Italy (at 45.6 to 41.5 oN), Scotland (at 58.2 to 55.1 oN), and Spain (at 41.5 oN). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as comparator, the median 25(OH)D concentration was 3.03, 3.28, 5.41, 6.54, and 9.28 ng/mL lower in the German, Finnish, Italian, Scottish, and Spanish cohort, respectively (P-value < 0.001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.
Published: 2022
Full Text: View/download PDF

32. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022
Full Text: View/download PDF

33. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022
Full Text: View/download PDF

34. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022
Full Text: View/download PDF

35. Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium

Author: Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, Söderberg, Stefan, Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, and Söderberg, Stefan
Abstract: Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25[OH]D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in 6 European countries by using harmonized immunoassay data from 81,084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48.9%; median age 50.8 years; examination period 1984 to 2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling, and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65.6 to 63.8 oN), Germany (at 48.4 oN), Finland (at 65.0 to 60.2 oN), Italy (at 45.6 to 41.5 oN), Scotland (at 58.2 to 55.1 oN), and Spain (at 41.5 oN). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as comparator, the median 25(OH)D concentration was 3.03, 3.28, 5.41, 6.54, and 9.28 ng/mL lower in the German, Finnish, Italian, Scottish, and Spanish cohort, respectively (P-value < 0.001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.
Published: 2022
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36. Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium

Author: Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, Söderberg, Stefan, Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, and Söderberg, Stefan
Abstract: Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25[OH]D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in 6 European countries by using harmonized immunoassay data from 81,084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48.9%; median age 50.8 years; examination period 1984 to 2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling, and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65.6 to 63.8 oN), Germany (at 48.4 oN), Finland (at 65.0 to 60.2 oN), Italy (at 45.6 to 41.5 oN), Scotland (at 58.2 to 55.1 oN), and Spain (at 41.5 oN). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as comparator, the median 25(OH)D concentration was 3.03, 3.28, 5.41, 6.54, and 9.28 ng/mL lower in the German, Finnish, Italian, Scottish, and Spanish cohort, respectively (P-value < 0.001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.
Published: 2022
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37. Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium

Author: Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, Söderberg, Stefan, Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, and Söderberg, Stefan
Abstract: Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25[OH]D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in 6 European countries by using harmonized immunoassay data from 81,084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48.9%; median age 50.8 years; examination period 1984 to 2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling, and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65.6 to 63.8 oN), Germany (at 48.4 oN), Finland (at 65.0 to 60.2 oN), Italy (at 45.6 to 41.5 oN), Scotland (at 58.2 to 55.1 oN), and Spain (at 41.5 oN). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as comparator, the median 25(OH)D concentration was 3.03, 3.28, 5.41, 6.54, and 9.28 ng/mL lower in the German, Finnish, Italian, Scottish, and Spanish cohort, respectively (P-value < 0.001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.
Published: 2022
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38. Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium

Author: Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, Söderberg, Stefan, Oskarsson, Viktor, Eliasson, Mats, Salomaa, Veikko, Reinikainen, Jaakko, Männistö, Satu, Palmieri, Luigi, Donfrancesco, Chiara, Sans, Susana, Costanzo, Simona, De Gaetano, Giovanni, Iacoviello, Licia, Veronesi, Giovanni, Ferrario, Marco M, Padro, Teresa, Thorand, Barbara, Huth, Cornelia, Zeller, Tanja, Blankenberg, Stefan, Anderson, Annie S, Tunstall-Pedoe, Hugh, Kuulasmaa, Kari, and Söderberg, Stefan
Abstract: Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25[OH]D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in 6 European countries by using harmonized immunoassay data from 81,084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48.9%; median age 50.8 years; examination period 1984 to 2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling, and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65.6 to 63.8 oN), Germany (at 48.4 oN), Finland (at 65.0 to 60.2 oN), Italy (at 45.6 to 41.5 oN), Scotland (at 58.2 to 55.1 oN), and Spain (at 41.5 oN). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as comparator, the median 25(OH)D concentration was 3.03, 3.28, 5.41, 6.54, and 9.28 ng/mL lower in the German, Finnish, Italian, Scottish, and Spanish cohort, respectively (P-value < 0.001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.
Published: 2022
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39. Development and validation of a model to predict incident chronic liver disease in the general population:The CLivD score

Author: Åberg, Fredrik, Luukkonen, Panu K., But, Anna, Salomaa, Veikko, Britton, Annie, Petersen, Kasper Meidahl, Bojesen, Stig Egil, Balling, Mie, Nordestgaard, Børge G., Puukka, Pauli, Männistö, Satu, Lundqvist, Annamari, Perola, Markus, Jula, Antti, Färkkilä, Martti, Åberg, Fredrik, Luukkonen, Panu K., But, Anna, Salomaa, Veikko, Britton, Annie, Petersen, Kasper Meidahl, Bojesen, Stig Egil, Balling, Mie, Nordestgaard, Børge G., Puukka, Pauli, Männistö, Satu, Lundqvist, Annamari, Perola, Markus, Jula, Antti, and Färkkilä, Martti
Abstract: Background & Aims: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk prediction model for incident chronic liver disease in the general population based on widely available factors. Methods: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40–70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. Results: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist–hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers’ C-statistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (<2%) of the population with >10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. Conclusions: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. Lay summary: Liver disease often progresses silently without
Published: 2022

40. Development and validation of a model to predict incident chronic liver disease in the general population:The CLivD score

Author: Åberg, Fredrik, Luukkonen, Panu K., But, Anna, Salomaa, Veikko, Britton, Annie, Petersen, Kasper Meidahl, Bojesen, Stig Egil, Balling, Mie, Nordestgaard, Børge G., Puukka, Pauli, Männistö, Satu, Lundqvist, Annamari, Perola, Markus, Jula, Antti, Färkkilä, Martti, Åberg, Fredrik, Luukkonen, Panu K., But, Anna, Salomaa, Veikko, Britton, Annie, Petersen, Kasper Meidahl, Bojesen, Stig Egil, Balling, Mie, Nordestgaard, Børge G., Puukka, Pauli, Männistö, Satu, Lundqvist, Annamari, Perola, Markus, Jula, Antti, and Färkkilä, Martti
Abstract: Background & Aims: Current screening strategies for chronic liver disease focus on detection of subclinical advanced liver fibrosis but cannot identify those at high future risk of severe liver disease. Our aim was to develop and validate a risk prediction model for incident chronic liver disease in the general population based on widely available factors. Methods: Multivariable Cox regression analyses were used to develop prediction models for liver-related outcomes with and without laboratory measures (Modellab and Modelnon-lab) in 25,760 individuals aged 40–70 years. Their data were sourced from the Finnish population-based health examination surveys FINRISK 1992-2012 and Health 2000 (derivation cohort). The models were externally validated in the Whitehall II (n = 5,058) and Copenhagen City Heart Study (CCHS) (n = 3,049) cohorts. Results: The absolute rate of incident liver outcomes per 100,000 person-years ranged from 53 to 144. The final prediction model included age, sex, alcohol use (drinks/week), waist–hip ratio, diabetes, and smoking, and Modellab also included gamma-glutamyltransferase values. Internally validated Wolbers’ C-statistics were 0.77 for Modellab and 0.75 for Modelnon-lab, while apparent 15-year AUCs were 0.84 (95% CI 0.75-0.93) and 0.82 (95% CI 0.74-0.91). The models identified a small proportion (<2%) of the population with >10% absolute 15-year risk for liver events. Of all liver events, only 10% occurred in participants in the lowest risk category. In the validation cohorts, 15-year AUCs were 0.78 (Modellab) and 0.65 (Modelnon-lab) in the CCHS cohort, and 0.78 (Modelnon-lab) in the Whitehall II cohort. Conclusions: Based on widely available risk factors, the Chronic Liver Disease (CLivD) score can be used to predict risk of future advanced liver disease in the general population. Lay summary: Liver disease often progresses silently without
Published: 2022

41. Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., and Travis, Ruth C.
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
Published: 2022
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42. The association of high-sensitivity C-reactive protein with future weight gain in adults

Author: Santa-Paavola, Riina, Lehtinen-Jacks, Susanna, Jääskeläinen, Tuija, Männistö, Satu, Lundqvist, Annamari, Santa-Paavola, Riina, Lehtinen-Jacks, Susanna, Jääskeläinen, Tuija, Männistö, Satu, and Lundqvist, Annamari
Abstract: Background: Obesity is associated with low-grade systemic inflammation, and it has been suggested that increased inflammation markers could predict future weight gain. Our aim was to investigate the associations of high-sensitivity C-reactive protein (hs-CRP) concentration with changes in weight and waist circumference in adults during 11 years of follow-up. Methods: We used data from the Health 2000 and Health 2011 surveys consisting of a population-based sample of Finnish adults. We included those 3143 participants, aged 30-75 years at baseline, whose baseline hs-CRP was measured, and who had information on measured weight and height at both time points. Associations between baseline hs-CRP and changes in weight and waist circumference were analyzed using multinomial logistic regression, adjusted for sociodemographic factors (age, sex, marital status, and educational status), lifestyle factors (smoking, alcohol consumption, leisure-time physical activity, sitting time, sleeping time, and psychological distress), and baseline values of BMI and waist circumference. Results: Hs-CRP was not associated with weight gain (≥5%) when adjusted for potential confounders (OR 0.99, 95% CI 0.96-1.01), compared to stable weight (change <±5%). Higher baseline hs-CRP was associated with decrease in weight (≤-5%) in the unadjusted (OR 1.03, 1.01-1.05), but not in the adjusted (OR 1.01, 0.99-1.03) model. No association was observed between hs-CRP and waist circumference.
Published: 2022
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43. Circulating free testosterone and risk of aggressive prostate cancer : Prospective and Mendelian randomisation analyses in international consortia

Author: Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., Travis, Ruth C., Watts, Eleanor L., Perez-Cornago, Aurora, Fensom, Georgina K., Smith-Byrne, Karl, Noor, Urwah, Andrews, Colm D., Gunter, Marc J., Holmes, Michael V., Martin, Richard M., Tsilidis, Konstantinos K., Albanes, Demetrius, Barricarte, Aurelio, Bueno-de-Mesquita, Bas, Chen, Chu, Cohn, Barbara A., Dimou, Niki L., Ferrucci, Luigi, Flicker, Leon, Freedman, Neal D., Giles, Graham G., Giovannucci, Edward L., Goodman, Gary E., Haiman, Christopher A., Hankey, Graeme J., Huang, Jiaqi, Huang, Wen-Yi, Hurwitz, Lauren M., Kaaks, Rudolf, Knekt, Paul, Kubo, Tatsuhiko, Langseth, Hilde, Laughlin, Gail, Le Marchand, Loic, Luostarinen, Tapio, MacInnis, Robert J., Mäenpää, Hanna O., Männistö, Satu, Metter, Jeffrey E., Mikami, Kazuya, Mucci, Lorelei A., Olsen, Anja W., Ozasa, Kotaro, Palli, Domenico, Penney, Kathryn L., Platz, Elizabeth A., Rissanen, Harri, Sawada, Norie, Schenk, Jeannette M., Stattin, Pär, Tamakoshi, Akiko, Thysell, Elin, Tsai, Chiaojung Jillian, Tsugane, Shoichiro, Vatten, Lars, Weiderpass, Elisabete, Weinstein, Stephanie J., Wilkens, Lynne R., Yeap, Bu B., Allen, Naomi E., Key, Timothy J., and Travis, Ruth C.
Abstract: Previous studies had limited power to assess the associations of testosterone with aggressive disease as a primary endpoint. Further, the association of genetically predicted testosterone with aggressive disease is not known. We investigated the associations of calculated free and measured total testosterone and sex hormone-binding globulin (SHBG) with aggressive, overall and early-onset prostate cancer. In blood-based analyses, odds ratios (OR) and 95% confidence intervals (CI) for prostate cancer were estimated using conditional logistic regression from prospective analysis of biomarker concentrations in the Endogenous Hormones, Nutritional Biomarkers and Prostate Cancer Collaborative Group (up to 25 studies, 14 944 cases and 36 752 controls, including 1870 aggressive prostate cancers). In Mendelian randomisation (MR) analyses, using instruments identified using UK Biobank (up to 194 453 men) and outcome data from PRACTICAL (up to 79 148 cases and 61 106 controls, including 15 167 aggressive cancers), ORs were estimated using the inverse-variance weighted method. Free testosterone was associated with aggressive disease in MR analyses (OR per 1 SD = 1.23, 95% CI = 1.08-1.40). In blood-based analyses there was no association with aggressive disease overall, but there was heterogeneity by age at blood collection (OR for men aged <60 years 1.14, CI = 1.02-1.28; Phet =.0003: inverse association for older ages). Associations for free testosterone were positive for overall prostate cancer (MR: 1.20, 1.08-1.34; blood-based: 1.03, 1.01-1.05) and early-onset prostate cancer (MR: 1.37, 1.09-1.73; blood-based: 1.08, 0.98-1.19). SHBG and total testosterone were inversely associated with overall prostate cancer in blood-based analyses, with null associations in MR analysis. Our results support free testosterone, rather than total testosterone, in the development of prostate cancer, including aggressive subgroups.
Published: 2022
Full Text: View/download PDF

44. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project:a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022

45. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project:a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022

46. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022
Full Text: View/download PDF

47. Alcohol intake and total mortality in 142 960 individuals from the MORGAM Project: a population-based study

Author: Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, Iacoviello, Licia, Di Castelnuovo, Augusto, Costanzo, Simona, Bonaccio, Marialaura, McElduff, Patrick, Linneberg, Allan, Salomaa, Veikko, Männistö, Satu, Moitry, Marie, Ferrières, Jean, Dallongeville, Jean, Thorand, Barbara, Brenner, Hermann, Ferrario, Marco, Veronesi, Giovanni, Pettenuzzo, Emanuela, Tamosiunas, Abdonas, Njølstad, Inger, Drygas, Wojciech, Nikitin, Yuri, Söderberg, Stefan, Kee, Frank, Grassi, Guido, Westermann, Dirk, Schrage, Benedikt, Dabboura, Salim, Zeller, Tanja, Kuulasmaa, Kari, Blankenberg, Stefan, Donati, Maria Benedetta, de Gaetano, Giovanni, and Iacoviello, Licia
Abstract: Aim: To test the association of alcohol consumption with total and cause-specific mortality risk. Design: Prospective observational multi-centre population-based study. Setting: Sixteen cohorts (15 from Europe) in the MOnica Risk, Genetics, Archiving and Monograph (MORGAM) Project. Participants: A total of 142 960 individuals (mean age 50 ± 13 years, 53.9% men). Measurements: Average alcohol intake by food frequency questionnaire, total and cause-specific mortality. Findings: In comparison with life-time abstainers, consumption of alcohol less than 10 g/day was associated with an average 11% [95% confidence interval (CI) = 7–14%] reduction in the risk of total mortality, while intake > 20 g/day was associated with a 13% (95% CI = 7–20%) increase in the risk of total mortality. Comparable findings were observed for cardiovascular (CV) deaths. With regard to cancer, drinking up to 10 g/day was not associated with either mortality risk reduction or increase, while alcohol intake > 20 g/day was associated with a 22% (95% CI = 10–35%) increased risk of mortality. The association of alcohol with fatal outcomes was similar in men and women, differed somewhat between countries and was more apparent in individuals preferring wine, suggesting that benefits may not be due to ethanol but other ingredients. Mediation analysis showed that high-density lipoprotein cholesterol explained 2.9 and 18.7% of the association between low alcohol intake and total as well as CV mortality, respectively. Conclusions: In comparison with life-time abstainers, consuming less than one drink per day (nadir at 5 g/day) was associated with a reduced risk of total, cardiovascular and other causes mortality, except cancer. Intake of more than two drinks per day was associated with an increased risk of total, cardiovascular and especially cancer mortality.
Published: 2022
Full Text: View/download PDF

48. Shared genetic risk between eating disorder- and substance-use-related phenotypes: Evidence from genome-wide association studies

Author: Munn-Chernoff, Melissa A, Johnson, Emma C, Chou, Yi-Ling, Coleman, Jonathan R I, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger A H, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver S P, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J H, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klump, Kelly L, Knudsen, Gun Peggy S, La Via, Maria C, Le Hellard, Stephanie, Levitan, Robert D, Li, Dong, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre J, Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian R, Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Karen, Monteleone, Alessio Maria, Monteleone, Palmiero, Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, O'Toole, Julie K, Ophoff, Roel A, Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W, Schmidt, Ulrike, Schork, Nicholas J, Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P Eline, Slof-Op't Landt, Margarita C T, Slopien, Agnieszka, Sorbi, Sandro, Świątkowska, Beata, Szatkiewicz, Jin P, Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A, van Furth, Eric F, Wagner, Gudrun, Walton, Esther, Widen, Elisabeth, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Bergen, Andrew W, Boden, Joseph M, Brandt, Harry, Crawford, Steven, Halmi, Katherine A, Horwood, L John, Johnson, Craig, Kaplan, Allan S, Kaye, Walter H, Mitchell, James, Olsen, Catherine M, Pearson, John F, Pedersen, Nancy L, Strober, Michael, Werge, Thomas, Whiteman, David C, Woodside, D Blake, Grove, Jakob, Henders, Anjali K, Larsen, Janne T, Parker, Richard, Petersen, Liselotte V, Jordan, Jennifer, Kennedy, Martin A, Birgegård, Andreas, Lichtenstein, Paul, Norring, Claes, Landén, Mikael, Mortensen, Preben Bo, Polimanti, Renato, McClintick, Jeanette N, Adkins, Amy E, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M, Bigdeli, Tim B, Chen, Li-Shiun, Clarke, Toni-Kim, Degenhardt, Franziska, Docherty, Anna R, Edwards, Alexis C, Foo, Jerome C, Fox, Louis, Frank, Josef, Hack, Laura M, Hartmann, Annette M, Hartz, Sarah M, Heilmann-Heimbach, Stefanie, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke-Jan, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S, Mbarek, Hamdi, McIntosh, Andrew M, McQueen, Matthew B, Meyers, Jacquelyn L, Milaneschi, Yuri, Palviainen, Teemu, Peterson, Roseann E, Ryu, Euijung, Saccone, Nancy L, Salvatore, Jessica E, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley T, Wedow, Robbee, Wetherill, Leah, Wills, Amanda G, Zhou, Hang, Boardman, Jason D, Chen, Danfeng, Choi, Doo-Sup, Copeland, William E, Culverhouse, Robert C, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W, Frye, Mark A, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Koller, Gabriele, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D, Nurnberger, John I, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A, Soyka, Michael, Treutlein, Jens, Witt, Stephanie H, Wodarz, Norbert, Zill, Peter, Adkins, Daniel E, Boomsma, Dorret I, Bierut, Laura J, Brown, Sandra A, Bucholz, Kathleen K, Costello, E Jane, de Wit, Harriet, Diazgranados, Nancy, Eriksson, Johan G, Farrer, Lindsay A, Foroud, Tatiana M, Gillespie, Nathan A, Goate, Alison M, Goldman, David, Grucza, Richard A, Hancock, Dana B, Harris, Kathleen Mullan, Hesselbrock, Victor, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Johnson, Eric O, Karpyak, Victor M, Kendler, Kenneth S, Kranzler, Henry R, Krauter, Kenneth, Lind, Penelope A, McGue, Matt, MacKillop, James, Madden, Pamela A F, Maes, Hermine H, Magnusson, Patrik K E, Nelson, Elliot C, Nöthen, Markus M, Palmer, Abraham A, Penninx, Brenda W J H, Porjesz, Bernice, Rice, John P, Rietschel, Marcella, Riley, Brien P, Rose, Richard J, Shen, Pei-Hong, Silberg, Judy, Stallings, Michael C, Tarter, Ralph E, Vanyukov, Michael M, Vrieze, Scott, Wall, Tamara L, Whitfield, John B, Zhao, Hongyu, Neale, Benjamin M, Wade, Tracey D, Heath, Andrew C, Montgomery, Grant W, Martin, Nicholas G, Sullivan, Patrick F, Kaprio, Jaakko, Breen, Gerome, Gelernter, Joel, Edenberg, Howard J, Bulik, Cynthia M, Agrawal, Arpana, Munn-Chernoff, Melissa A, Johnson, Emma C, Chou, Yi-Ling, Coleman, Jonathan R I, Thornton, Laura M, Walters, Raymond K, Yilmaz, Zeynep, Baker, Jessica H, Hübel, Christopher, Gordon, Scott, Medland, Sarah E, Watson, Hunna J, Gaspar, Héléna A, Bryois, Julien, Hinney, Anke, Leppä, Virpi M, Mattheisen, Manuel, Ripke, Stephan, Yao, Shuyang, Giusti-Rodríguez, Paola, Hanscombe, Ken B, Adan, Roger A H, Alfredsson, Lars, Ando, Tetsuya, Andreassen, Ole A, Berrettini, Wade H, Boehm, Ilka, Boni, Claudette, Boraska Perica, Vesna, Buehren, Katharina, Burghardt, Roland, Cassina, Matteo, Cichon, Sven, Clementi, Maurizio, Cone, Roger D, Courtet, Philippe, Crow, Scott, Crowley, James J, Danner, Unna N, Davis, Oliver S P, de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E, Dick, Danielle M, Dikeos, Dimitris, Dina, Christian, Dmitrzak-Weglarz, Monika, Docampo, Elisa, Duncan, Laramie E, Egberts, Karin, Ehrlich, Stefan, Escaramís, Geòrgia, Esko, Tõnu, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M, Fischer, Krista, Föcker, Manuel, Foretova, Lenka, Forstner, Andreas J, Forzan, Monica, Franklin, Christopher S, Gallinger, Steven, Giegling, Ina, Giuranna, Johanna, Gonidakis, Fragiskos, Gorwood, Philip, Gratacos Mayora, Monica, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Hatzikotoulas, Konstantinos, Hauser, Joanna, Hebebrand, Johannes, Helder, Sietske G, Herms, Stefan, Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Huckins, Laura M, Hudson, James I, Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J H, Kennedy, James L, Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Klump, Kelly L, Knudsen, Gun Peggy S, La Via, Maria C, Le Hellard, Stephanie, Levitan, Robert D, Li, Dong, Lilenfeld, Lisa, Lin, Bochao Danae, Lissowska, Jolanta, Luykx, Jurjen, Magistretti, Pierre J, Maj, Mario, Mannik, Katrin, Marsal, Sara, Marshall, Christian R, Mattingsdal, Morten, McDevitt, Sara, McGuffin, Peter, Metspalu, Andres, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, Karen, Monteleone, Alessio Maria, Monteleone, Palmiero, Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, O'Toole, Julie K, Ophoff, Roel A, Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Pinto, Dalila, Rabionet, Raquel, Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rotondo, Alessandro, Rujescu, Dan, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W, Schmidt, Ulrike, Schork, Nicholas J, Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P Eline, Slof-Op't Landt, Margarita C T, Slopien, Agnieszka, Sorbi, Sandro, Świątkowska, Beata, Szatkiewicz, Jin P, Tachmazidou, Ioanna, Tenconi, Elena, Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A, van Furth, Eric F, Wagner, Gudrun, Walton, Esther, Widen, Elisabeth, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Bergen, Andrew W, Boden, Joseph M, Brandt, Harry, Crawford, Steven, Halmi, Katherine A, Horwood, L John, Johnson, Craig, Kaplan, Allan S, Kaye, Walter H, Mitchell, James, Olsen, Catherine M, Pearson, John F, Pedersen, Nancy L, Strober, Michael, Werge, Thomas, Whiteman, David C, Woodside, D Blake, Grove, Jakob, Henders, Anjali K, Larsen, Janne T, Parker, Richard, Petersen, Liselotte V, Jordan, Jennifer, Kennedy, Martin A, Birgegård, Andreas, Lichtenstein, Paul, Norring, Claes, Landén, Mikael, Mortensen, Preben Bo, Polimanti, Renato, McClintick, Jeanette N, Adkins, Amy E, Aliev, Fazil, Bacanu, Silviu-Alin, Batzler, Anthony, Bertelsen, Sarah, Biernacka, Joanna M, Bigdeli, Tim B, Chen, Li-Shiun, Clarke, Toni-Kim, Degenhardt, Franziska, Docherty, Anna R, Edwards, Alexis C, Foo, Jerome C, Fox, Louis, Frank, Josef, Hack, Laura M, Hartmann, Annette M, Hartz, Sarah M, Heilmann-Heimbach, Stefanie, Hodgkinson, Colin, Hoffmann, Per, Hottenga, Jouke-Jan, Konte, Bettina, Lahti, Jari, Lahti-Pulkkinen, Marius, Lai, Dongbing, Ligthart, Lannie, Loukola, Anu, Maher, Brion S, Mbarek, Hamdi, McIntosh, Andrew M, McQueen, Matthew B, Meyers, Jacquelyn L, Milaneschi, Yuri, Palviainen, Teemu, Peterson, Roseann E, Ryu, Euijung, Saccone, Nancy L, Salvatore, Jessica E, Sanchez-Roige, Sandra, Schwandt, Melanie, Sherva, Richard, Streit, Fabian, Strohmaier, Jana, Thomas, Nathaniel, Wang, Jen-Chyong, Webb, Bradley T, Wedow, Robbee, Wetherill, Leah, Wills, Amanda G, Zhou, Hang, Boardman, Jason D, Chen, Danfeng, Choi, Doo-Sup, Copeland, William E, Culverhouse, Robert C, Dahmen, Norbert, Degenhardt, Louisa, Domingue, Benjamin W, Frye, Mark A, Gäbel, Wolfgang, Hayward, Caroline, Ising, Marcus, Keyes, Margaret, Kiefer, Falk, Koller, Gabriele, Kramer, John, Kuperman, Samuel, Lucae, Susanne, Lynskey, Michael T, Maier, Wolfgang, Mann, Karl, Männistö, Satu, Müller-Myhsok, Bertram, Murray, Alison D, Nurnberger, John I, Preuss, Ulrich, Räikkönen, Katri, Reynolds, Maureen D, Ridinger, Monika, Scherbaum, Norbert, Schuckit, Marc A, Soyka, Michael, Treutlein, Jens, Witt, Stephanie H, Wodarz, Norbert, Zill, Peter, Adkins, Daniel E, Boomsma, Dorret I, Bierut, Laura J, Brown, Sandra A, Bucholz, Kathleen K, Costello, E Jane, de Wit, Harriet, Diazgranados, Nancy, Eriksson, Johan G, Farrer, Lindsay A, Foroud, Tatiana M, Gillespie, Nathan A, Goate, Alison M, Goldman, David, Grucza, Richard A, Hancock, Dana B, Harris, Kathleen Mullan, Hesselbrock, Victor, Hewitt, John K, Hopfer, Christian J, Iacono, William G, Johnson, Eric O, Karpyak, Victor M, Kendler, Kenneth S, Kranzler, Henry R, Krauter, Kenneth, Lind, Penelope A, McGue, Matt, MacKillop, James, Madden, Pamela A F, Maes, Hermine H, Magnusson, Patrik K E, Nelson, Elliot C, Nöthen, Markus M, Palmer, Abraham A, Penninx, Brenda W J H, Porjesz, Bernice, Rice, John P, Rietschel, Marcella, Riley, Brien P, Rose, Richard J, Shen, Pei-Hong, Silberg, Judy, Stallings, Michael C, Tarter, Ralph E, Vanyukov, Michael M, Vrieze, Scott, Wall, Tamara L, Whitfield, John B, Zhao, Hongyu, Neale, Benjamin M, Wade, Tracey D, Heath, Andrew C, Montgomery, Grant W, Martin, Nicholas G, Sullivan, Patrick F, Kaprio, Jaakko, Breen, Gerome, Gelernter, Joel, Edenberg, Howard J, Bulik, Cynthia M, and Agrawal, Arpana
Abstract: Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-sp
Published: 2021
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49. Genetic architectures of proximal and distal colorectal cancer are partly distinct

Author: Huyghe, Jeroen R, Harrison, Tabitha A, Bien, Stephanie A, Hampel, Heather, Figueiredo, Jane C, Schmit, Stephanie L, Conti, David V, Chen, Sai, Qu, Conghui, Lin, Yi, Barfield, Richard, Baron, John A, Cross, Amanda J, Diergaarde, Brenda, Duggan, David, Harlid, Sophia, Imaz, Liher, Kang, Hyun Min, Levine, David M, Perduca, Vittorio, Perez-Cornago, Aurora, Sakoda, Lori C, Schumacher, Fredrick R, Slattery, Martha L, Toland, Amanda E, van Duijnhoven, Fränzel J B, Van Guelpen, Bethany, Agudo, Antonio, Albanes, Demetrius, Alonso, M Henar, Anderson, Kristin, Arnau-Collell, Coral, Arndt, Volker, Banbury, Barbara L, Bassik, Michael C, Berndt, Sonja I, Bézieau, Stéphane, Bishop, D Timothy, Boehm, Juergen, Boeing, Heiner, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buch, Stephan, Buchanan, Daniel D, Burnett-Hartman, Andrea, Caan, Bette J, Campbell, Peter T, Carr, Prudence R, Castells, Antoni, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Curtis, Keith R, de la Chapelle, Albert, Easton, Douglas F, English, Dallas R, Feskens, Edith J M, Gala, Manish, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Goodman, Phyllis J, Grady, William M, Grove, John S, Gsur, Andrea, Gunter, Marc J, Haile, Robert W, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Wan-Ling, Huang, Wen-Yi, Hudson, Thomas J, Jenab, Mazda, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Kooperberg, Charles, Kühn, Tilman, Küry, Sébastien, Le Marchand, Loic, Lejbkowicz, Flavio, Li, Christopher I, Li, Li, Lieb, Wolfgang, Lindblom, Annika, Lindor, Noralane M, Männistö, Satu, Markowitz, Sanford D, Milne, Roger L, Moreno, Lorena, Murphy, Neil, Nassir, Rami, Offit, Kenneth, Ogino, Shuji, Panico, Salvatore, Parfrey, Patrick S, Pearlman, Rachel, Pharoah, Paul D P, Phipps, Amanda I, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Qi, Lihong, Raskin, Leon, Rennert, Gad, Rennert, Hedy S, Riboli, Elio, Schafmayer, Clemens, Schoen, Robert E, Seminara, Daniela, Song, Mingyang, Su, Yu-Ru, Tangen, Catherine M, Thibodeau, Stephen N, Thomas, Duncan C, Trichopoulou, Antonia, Ulrich, Cornelia M, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Weigl, Korbinian, Weinstein, Stephanie J, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Abecasis, Goncalo R, Nickerson, Deborah A, Scacheri, Peter C, Kundaje, Anshul, Casey, Graham, Gruber, Stephen B, Hsu, Li, Moreno, Victor, Hayes, Richard B, Newcomb, Polly A, Peters, Ulrike, Huyghe, Jeroen R, Harrison, Tabitha A, Bien, Stephanie A, Hampel, Heather, Figueiredo, Jane C, Schmit, Stephanie L, Conti, David V, Chen, Sai, Qu, Conghui, Lin, Yi, Barfield, Richard, Baron, John A, Cross, Amanda J, Diergaarde, Brenda, Duggan, David, Harlid, Sophia, Imaz, Liher, Kang, Hyun Min, Levine, David M, Perduca, Vittorio, Perez-Cornago, Aurora, Sakoda, Lori C, Schumacher, Fredrick R, Slattery, Martha L, Toland, Amanda E, van Duijnhoven, Fränzel J B, Van Guelpen, Bethany, Agudo, Antonio, Albanes, Demetrius, Alonso, M Henar, Anderson, Kristin, Arnau-Collell, Coral, Arndt, Volker, Banbury, Barbara L, Bassik, Michael C, Berndt, Sonja I, Bézieau, Stéphane, Bishop, D Timothy, Boehm, Juergen, Boeing, Heiner, Boutron-Ruault, Marie-Christine, Brenner, Hermann, Brezina, Stefanie, Buch, Stephan, Buchanan, Daniel D, Burnett-Hartman, Andrea, Caan, Bette J, Campbell, Peter T, Carr, Prudence R, Castells, Antoni, Castellví-Bel, Sergi, Chan, Andrew T, Chang-Claude, Jenny, Chanock, Stephen J, Curtis, Keith R, de la Chapelle, Albert, Easton, Douglas F, English, Dallas R, Feskens, Edith J M, Gala, Manish, Gallinger, Steven J, Gauderman, W James, Giles, Graham G, Goodman, Phyllis J, Grady, William M, Grove, John S, Gsur, Andrea, Gunter, Marc J, Haile, Robert W, Hampe, Jochen, Hoffmeister, Michael, Hopper, John L, Hsu, Wan-Ling, Huang, Wen-Yi, Hudson, Thomas J, Jenab, Mazda, Jenkins, Mark A, Joshi, Amit D, Keku, Temitope O, Kooperberg, Charles, Kühn, Tilman, Küry, Sébastien, Le Marchand, Loic, Lejbkowicz, Flavio, Li, Christopher I, Li, Li, Lieb, Wolfgang, Lindblom, Annika, Lindor, Noralane M, Männistö, Satu, Markowitz, Sanford D, Milne, Roger L, Moreno, Lorena, Murphy, Neil, Nassir, Rami, Offit, Kenneth, Ogino, Shuji, Panico, Salvatore, Parfrey, Patrick S, Pearlman, Rachel, Pharoah, Paul D P, Phipps, Amanda I, Platz, Elizabeth A, Potter, John D, Prentice, Ross L, Qi, Lihong, Raskin, Leon, Rennert, Gad, Rennert, Hedy S, Riboli, Elio, Schafmayer, Clemens, Schoen, Robert E, Seminara, Daniela, Song, Mingyang, Su, Yu-Ru, Tangen, Catherine M, Thibodeau, Stephen N, Thomas, Duncan C, Trichopoulou, Antonia, Ulrich, Cornelia M, Visvanathan, Kala, Vodicka, Pavel, Vodickova, Ludmila, Vymetalkova, Veronika, Weigl, Korbinian, Weinstein, Stephanie J, White, Emily, Wolk, Alicja, Woods, Michael O, Wu, Anna H, Abecasis, Goncalo R, Nickerson, Deborah A, Scacheri, Peter C, Kundaje, Anshul, Casey, Graham, Gruber, Stephen B, Hsu, Li, Moreno, Victor, Hayes, Richard B, Newcomb, Polly A, and Peters, Ulrike
Abstract: Objective: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. Design: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. Results: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. Conclusion: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour.
Published: 2021
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50. Prevalent diabetes and risk of total, colorectal, prostate and breast cancers in an ageing population : meta-analysis of individual participant data from cohorts of the CHANCES consortium

Author: Amadou, Amina, Freisling, Heinz, Jenab, Mazda, Tsilidis, Konstantinos K., Trichopoulou, Antonia, Boffetta, Paolo, van Guelpen, Bethany, Mokoroa, Olatz, Wilsgaard, Tom, Kee, Frank, Schöttker, Ben, Ordóñez-Mena, José M., Männistö, Satu, Söderberg, Stefan, Vermeulen, Roel C. H., Quirós, J. Ramón, Liao, Linda M., Sinha, Rashmi, Kuulasmaa, Kari, Brenner, Hermann, Romieu, Isabelle, Amadou, Amina, Freisling, Heinz, Jenab, Mazda, Tsilidis, Konstantinos K., Trichopoulou, Antonia, Boffetta, Paolo, van Guelpen, Bethany, Mokoroa, Olatz, Wilsgaard, Tom, Kee, Frank, Schöttker, Ben, Ordóñez-Mena, José M., Männistö, Satu, Söderberg, Stefan, Vermeulen, Roel C. H., Quirós, J. Ramón, Liao, Linda M., Sinha, Rashmi, Kuulasmaa, Kari, Brenner, Hermann, and Romieu, Isabelle
Abstract: Background: We investigated whether associations between prevalent diabetes and cancer risk are pertinent to older adults and whether associations differ across subgroups of age, body weight status or levels of physical activity. Methods: We harmonised data from seven prospective cohort studies of older individuals in Europe and the United States participating in the CHANCES consortium. Cox proportional hazard regression was used to estimate the associations of prevalent diabetes with cancer risk (all cancers combined, and for colorectum, prostate and breast). We calculated summary risk estimates across cohorts using pooled analysis and random-effects meta-analysis. Results: A total of 667,916 individuals were included with an overall median (P25–P75) age at recruitment of 62.3 (57–67) years. During a median follow-up time of 10.5 years, 114,404 total cancer cases were ascertained. Diabetes was not associated with the risk of all cancers combined (hazard ratio (HR) = 0.94; 95% confidence interval (CI): 0.86–1.04; I2 = 63.3%). Diabetes was positively associated with colorectal cancer risk in men (HR = 1.17; 95% CI: 1.08–1.26; I2 = 0%) and a similar HR in women (1.13; 95% CI: 0.82–1.56; I2 = 46%), but with a confidence interval including the null. Diabetes was inversely associated with prostate cancer risk (HR = 0.81; 95% CI: 0.77–0.85; I2 = 0%), but not with postmenopausal breast cancer (HR = 0.96; 95% CI: 0.89–1.03; I2 = 0%). In exploratory subgroup analyses, diabetes was inversely associated with prostate cancer risk only in men with overweight or obesity. Conclusions: Prevalent diabetes was positively associated with colorectal cancer risk and inversely associated with prostate cancer risk in older Europeans and Americans.
Published: 2021
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