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1. A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO

Author: Blackford, Amanda L., Childs, Erica J., Porter, Nancy, Petersen, Gloria M., Rabe, Kari G., Gallinger, Steven, Borgida, Ayelet, Syngal, Sapna, Cote, Michele L., Schwartz, Ann G., Goggins, Michael G., Hruban, Ralph H., Parmigiani, Giovanni, and Klein, Alison P.
Published: 2021
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2. Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies

Author: Julián-Serrano, Sachelly, Yuan, Fangcheng, Wheeler, William, Benyamin, Beben, Machiela, Mitchell J, Arslan, Alan A, Beane-Freeman, Laura E, Bracci, Paige M, Duell, Eric J, Du, Mengmeng, Gallinger, Steven, Giles, Graham G, Goodman, Phyllis J, Kooperberg, Charles, Marchand, Loic Le, Neale, Rachel E, Shu, Xiao-Ou, Van Den Eeden, Stephen K, Visvanathan, Kala, Zheng, Wei, Albanes, Demetrius, Andreotti, Gabriella, Ardanaz, Eva, Babic, Ana, Berndt, Sonja I, Brais, Lauren K, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie E, Chanock, Stephen J, Childs, Erica J, Chung, Charles C, Fabiánová, Eleonora, Foretová, Lenka, Fuchs, Charles S, Gaziano, J Michael, Gentiluomo, Manuel, Giovannucci, Edward L, Goggins, Michael G, Hackert, Thilo, Hartge, Patricia, Hassan, Manal M, Holcátová, Ivana, Holly, Elizabeth A, Hung, Rayjean I, Janout, Vladimir, Kurtz, Robert C, Lee, I-Min, Malats, Núria, McKean, David, Milne, Roger L, Newton, Christina C, Oberg, Ann L, Perdomo, Sandra, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Schulze, Matthias B, Sesso, Howard D, Silverman, Debra T, Thompson, Ian M, Wactawski-Wende, Jean, Weiderpass, Elisabete, Wenstzensen, Nicolas, White, Emily, Wilkens, Lynne R, Yu, Herbert, Zeleniuch-Jacquotte, Anne, Zhong, Jun, Kraft, Peter, Li, Dounghui, Campbell, Peter T, Petersen, Gloria M, Wolpin, Brian M, Risch, Harvey A, Amundadottir, Laufey T, Klein, Alison P, Yu, Kai, and Stolzenberg-Solomon, Rachael Z
Published: 2021
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3. Data from Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer

Author: Roberts, Nicholas J., primary, Norris, Alexis L., primary, Petersen, Gloria M., primary, Bondy, Melissa L., primary, Brand, Randall, primary, Gallinger, Steven, primary, Kurtz, Robert C., primary, Olson, Sara H., primary, Rustgi, Anil K., primary, Schwartz, Ann G., primary, Stoffel, Elena, primary, Syngal, Sapna, primary, Zogopoulos, George, primary, Ali, Syed Z., primary, Axilbund, Jennifer, primary, Chaffee, Kari G., primary, Chen, Yun-Ching, primary, Cote, Michele L., primary, Childs, Erica J., primary, Douville, Christopher, primary, Goes, Fernando S., primary, Herman, Joseph M., primary, Iacobuzio-Donahue, Christine, primary, Kramer, Melissa, primary, Makohon-Moore, Alvin, primary, McCombie, Richard W., primary, McMahon, K. Wyatt, primary, Niknafs, Noushin, primary, Parla, Jennifer, primary, Pirooznia, Mehdi, primary, Potash, James B., primary, Rhim, Andrew D., primary, Smith, Alyssa L., primary, Wang, Yuxuan, primary, Wolfgang, Christopher L., primary, Wood, Laura D., primary, Zandi, Peter P., primary, Goggins, Michael, primary, Karchin, Rachel, primary, Eshleman, James R., primary, Papadopoulos, Nickolas, primary, Kinzler, Kenneth W., primary, Vogelstein, Bert, primary, Hruban, Ralph H., primary, and Klein, Alison P., primary
Published: 2023
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4. Supplementary Tables S1 - S12 from Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer

Author: Roberts, Nicholas J., primary, Norris, Alexis L., primary, Petersen, Gloria M., primary, Bondy, Melissa L., primary, Brand, Randall, primary, Gallinger, Steven, primary, Kurtz, Robert C., primary, Olson, Sara H., primary, Rustgi, Anil K., primary, Schwartz, Ann G., primary, Stoffel, Elena, primary, Syngal, Sapna, primary, Zogopoulos, George, primary, Ali, Syed Z., primary, Axilbund, Jennifer, primary, Chaffee, Kari G., primary, Chen, Yun-Ching, primary, Cote, Michele L., primary, Childs, Erica J., primary, Douville, Christopher, primary, Goes, Fernando S., primary, Herman, Joseph M., primary, Iacobuzio-Donahue, Christine, primary, Kramer, Melissa, primary, Makohon-Moore, Alvin, primary, McCombie, Richard W., primary, McMahon, K. Wyatt, primary, Niknafs, Noushin, primary, Parla, Jennifer, primary, Pirooznia, Mehdi, primary, Potash, James B., primary, Rhim, Andrew D., primary, Smith, Alyssa L., primary, Wang, Yuxuan, primary, Wolfgang, Christopher L., primary, Wood, Laura D., primary, Zandi, Peter P., primary, Goggins, Michael, primary, Karchin, Rachel, primary, Eshleman, James R., primary, Papadopoulos, Nickolas, primary, Kinzler, Kenneth W., primary, Vogelstein, Bert, primary, Hruban, Ralph H., primary, and Klein, Alison P., primary
Published: 2023
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5. Supplementary Tables and Figures from Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study

Author: Childs, Erica J., primary, Chaffee, Kari G., primary, Gallinger, Steven, primary, Syngal, Sapna, primary, Schwartz, Ann G., primary, Cote, Michele L., primary, Bondy, Melissa L., primary, Hruban, Ralph H., primary, Chanock, Stephen J., primary, Hoover, Robert N., primary, Fuchs, Charles S., primary, Rider, David N., primary, Amundadottir, Laufey T., primary, Stolzenberg-Solomon, Rachael, primary, Wolpin, Brian M., primary, Risch, Harvey A., primary, Goggins, Michael G., primary, Petersen, Gloria M., primary, and Klein, Alison P., primary
Published: 2023
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6. Data from Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study

Author: Childs, Erica J., primary, Chaffee, Kari G., primary, Gallinger, Steven, primary, Syngal, Sapna, primary, Schwartz, Ann G., primary, Cote, Michele L., primary, Bondy, Melissa L., primary, Hruban, Ralph H., primary, Chanock, Stephen J., primary, Hoover, Robert N., primary, Fuchs, Charles S., primary, Rider, David N., primary, Amundadottir, Laufey T., primary, Stolzenberg-Solomon, Rachael, primary, Wolpin, Brian M., primary, Risch, Harvey A., primary, Goggins, Michael G., primary, Petersen, Gloria M., primary, and Klein, Alison P., primary
Published: 2023
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7. Supplementary table 8 from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author: Mocci, Evelina, primary, Kundu, Prosenjit, primary, Wheeler, William, primary, Arslan, Alan A., primary, Beane-Freeman, Laura E., primary, Bracci, Paige M., primary, Brennan, Paul, primary, Canzian, Federico, primary, Du, Mengmeng, primary, Gallinger, Steven, primary, Giles, Graham G., primary, Goodman, Phyllis J., primary, Kooperberg, Charles, primary, Le Marchand, Loic, primary, Neale, Rachel E., primary, Shu, Xiao-Ou, primary, Visvanathan, Kala, primary, White, Emily, primary, Zheng, Wei, primary, Albanes, Demetrius, primary, Andreotti, Gabriella, primary, Babic, Ana, primary, Bamlet, William R., primary, Berndt, Sonja I., primary, Blackford, Amanda L., primary, Bueno-de-Mesquita, Bas, primary, Buring, Julie E., primary, Campa, Daniele, primary, Chanock, Stephen J., primary, Childs, Erica J., primary, Duell, Eric J., primary, Fuchs, Charles S., primary, Gaziano, J. Michael, primary, Giovannucci, Edward L., primary, Goggins, Michael G., primary, Hartge, Patricia, primary, Hassan, Manal M., primary, Holly, Elizabeth A., primary, Hoover, Robert N., primary, Hung, Rayjean J., primary, Kurtz, Robert C., primary, Lee, I-Min, primary, Malats, Núria, primary, Milne, Roger L., primary, Ng, Kimmie, primary, Oberg, Ann L., primary, Panico, Salvatore, primary, Peters, Ulrike, primary, Porta, Miquel, primary, Rabe, Kari G., primary, Riboli, Elio, primary, Rothman, Nathaniel, primary, Scelo, Ghislaine, primary, Sesso, Howard D., primary, Silverman, Debra T., primary, Stevens, Victoria L., primary, Strobel, Oliver, primary, Thompson, Ian M., primary, Tjonneland, Anne, primary, Trichopoulou, Antonia, primary, Van Den Eeden, Stephen K., primary, Wactawski-Wende, Jean, primary, Wentzensen, Nicolas, primary, Wilkens, Lynne R., primary, Yu, Herbert, primary, Yuan, Fangcheng, primary, Zeleniuch-Jacquotte, Anne, primary, Amundadottir, Laufey T., primary, Li, Donghui, primary, Jacobs, Eric J., primary, Petersen, Gloria M., primary, Wolpin, Brian M., primary, Risch, Harvey A., primary, Kraft, Peter, primary, Chatterjee, Nilanjan, primary, Klein, Alison P., primary, and Stolzenberg-Solomon, Rachael, primary
Published: 2023
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8. Data from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author: Mocci, Evelina, primary, Kundu, Prosenjit, primary, Wheeler, William, primary, Arslan, Alan A., primary, Beane-Freeman, Laura E., primary, Bracci, Paige M., primary, Brennan, Paul, primary, Canzian, Federico, primary, Du, Mengmeng, primary, Gallinger, Steven, primary, Giles, Graham G., primary, Goodman, Phyllis J., primary, Kooperberg, Charles, primary, Le Marchand, Loic, primary, Neale, Rachel E., primary, Shu, Xiao-Ou, primary, Visvanathan, Kala, primary, White, Emily, primary, Zheng, Wei, primary, Albanes, Demetrius, primary, Andreotti, Gabriella, primary, Babic, Ana, primary, Bamlet, William R., primary, Berndt, Sonja I., primary, Blackford, Amanda L., primary, Bueno-de-Mesquita, Bas, primary, Buring, Julie E., primary, Campa, Daniele, primary, Chanock, Stephen J., primary, Childs, Erica J., primary, Duell, Eric J., primary, Fuchs, Charles S., primary, Gaziano, J. Michael, primary, Giovannucci, Edward L., primary, Goggins, Michael G., primary, Hartge, Patricia, primary, Hassan, Manal M., primary, Holly, Elizabeth A., primary, Hoover, Robert N., primary, Hung, Rayjean J., primary, Kurtz, Robert C., primary, Lee, I-Min, primary, Malats, Núria, primary, Milne, Roger L., primary, Ng, Kimmie, primary, Oberg, Ann L., primary, Panico, Salvatore, primary, Peters, Ulrike, primary, Porta, Miquel, primary, Rabe, Kari G., primary, Riboli, Elio, primary, Rothman, Nathaniel, primary, Scelo, Ghislaine, primary, Sesso, Howard D., primary, Silverman, Debra T., primary, Stevens, Victoria L., primary, Strobel, Oliver, primary, Thompson, Ian M., primary, Tjonneland, Anne, primary, Trichopoulou, Antonia, primary, Van Den Eeden, Stephen K., primary, Wactawski-Wende, Jean, primary, Wentzensen, Nicolas, primary, Wilkens, Lynne R., primary, Yu, Herbert, primary, Yuan, Fangcheng, primary, Zeleniuch-Jacquotte, Anne, primary, Amundadottir, Laufey T., primary, Li, Donghui, primary, Jacobs, Eric J., primary, Petersen, Gloria M., primary, Wolpin, Brian M., primary, Risch, Harvey A., primary, Kraft, Peter, primary, Chatterjee, Nilanjan, primary, Klein, Alison P., primary, and Stolzenberg-Solomon, Rachael, primary
Published: 2023
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9. Supplementary Data from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author: Mocci, Evelina, primary, Kundu, Prosenjit, primary, Wheeler, William, primary, Arslan, Alan A., primary, Beane-Freeman, Laura E., primary, Bracci, Paige M., primary, Brennan, Paul, primary, Canzian, Federico, primary, Du, Mengmeng, primary, Gallinger, Steven, primary, Giles, Graham G., primary, Goodman, Phyllis J., primary, Kooperberg, Charles, primary, Le Marchand, Loic, primary, Neale, Rachel E., primary, Shu, Xiao-Ou, primary, Visvanathan, Kala, primary, White, Emily, primary, Zheng, Wei, primary, Albanes, Demetrius, primary, Andreotti, Gabriella, primary, Babic, Ana, primary, Bamlet, William R., primary, Berndt, Sonja I., primary, Blackford, Amanda L., primary, Bueno-de-Mesquita, Bas, primary, Buring, Julie E., primary, Campa, Daniele, primary, Chanock, Stephen J., primary, Childs, Erica J., primary, Duell, Eric J., primary, Fuchs, Charles S., primary, Gaziano, J. Michael, primary, Giovannucci, Edward L., primary, Goggins, Michael G., primary, Hartge, Patricia, primary, Hassan, Manal M., primary, Holly, Elizabeth A., primary, Hoover, Robert N., primary, Hung, Rayjean J., primary, Kurtz, Robert C., primary, Lee, I-Min, primary, Malats, Núria, primary, Milne, Roger L., primary, Ng, Kimmie, primary, Oberg, Ann L., primary, Panico, Salvatore, primary, Peters, Ulrike, primary, Porta, Miquel, primary, Rabe, Kari G., primary, Riboli, Elio, primary, Rothman, Nathaniel, primary, Scelo, Ghislaine, primary, Sesso, Howard D., primary, Silverman, Debra T., primary, Stevens, Victoria L., primary, Strobel, Oliver, primary, Thompson, Ian M., primary, Tjonneland, Anne, primary, Trichopoulou, Antonia, primary, Van Den Eeden, Stephen K., primary, Wactawski-Wende, Jean, primary, Wentzensen, Nicolas, primary, Wilkens, Lynne R., primary, Yu, Herbert, primary, Yuan, Fangcheng, primary, Zeleniuch-Jacquotte, Anne, primary, Amundadottir, Laufey T., primary, Li, Donghui, primary, Jacobs, Eric J., primary, Petersen, Gloria M., primary, Wolpin, Brian M., primary, Risch, Harvey A., primary, Kraft, Peter, primary, Chatterjee, Nilanjan, primary, Klein, Alison P., primary, and Stolzenberg-Solomon, Rachael, primary
Published: 2023
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10. Detection of Intergenerational Genetic Effects with Application to HLA-B Matching as a Risk Factor for Schizophrenia

Author: Childs, Erica J., Sobel, Eric M., Palmer, Christina G. S., and Sinsheimer, Janet S.
Published: 2011

11. Abstract 885: A risk prediction tool for individuals with a family history of breast, ovarian, or pancreatic cancer: BRCAPANCPRO

Author: Blackford, Amanda L., primary, Childs, Erica J., additional, Porter, Nancy, additional, Petersen, Gloria, additional, Rabe, Kari, additional, Gallinger, Steven, additional, Borgida, Ayelet, additional, Syngal, Sapna, additional, Schwartz, Ann, additional, Cote, Michele, additional, Hruban, Ralph, additional, Goggins, Michael, additional, Klein, Alison P., additional, and Parmigiani, Giovanni, additional
Published: 2021
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12. Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author: Mocci, Evelina, Kundu, Prosenjit, Wheeler, William, Arslan, Alan A., Beane-Freeman, Laura E., Bracci, Paige M., Brennan, Paul, Canzian, Federico, Du, Mengmeng, Gallinger, Steven, Giles, Graham G., Goodman, Phyllis J., Kooperberg, Charles, Le Marchand, Loic, Neale, Rachel E., Shu, Xiao-Ou, Visvanathan, Kala, White, Emily, Zheng, Wei, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Bamlet, William R., Berndt, Sonja, Blackford, Amanda L., Bueno-de-Mesquita, Bas, Buring, Julie E., Campa, Daniele, Chanock, Stephen J., Childs, Erica J., Duell, Eric J., Fuchs, Charles S., Gaziano, J. Michael, Giovannucci, Edward L., Goggins, Michael G., Hartge, Patricia, Hassan, Manal M., Holly, Elizabeth A., Hoover, Robert N., Hung, Rayjean J., Kurtz, Robert C., Lee, I-Min, Malats, Nuria, Milne, Roger L., Ng, Kimmie, Oberg, Ann L., Panico, Salvatore, Peters, Ulrike, Porta, Miquel, Rabe, Kari G., Riboli, Elio, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Silverman, Debra T., Stevens, Victoria L., Strobel, Oliver, Thompson, Ian M., Tjonneland, Anne, Trichopoulou, Antonia, Van den Eeden, Stephen K., Wactawski-Wende, Jean, Wentzensen, Nicolas, Wilkens, Lynne R., Yu, Herbert, Yuan, Fangcheng, Zeleniuch-Jacquotte, Anne, Amundadottir, Laufey T., Li, Donghui, Jacobs, Eric J., Petersen, Gloria M., Wolpin, Brian M., Risch, Harvey A., Kraft, Peter, Chatterjee, Nilanjan, Klein, Alison P., Stolzenberg-Solomon, Rachael, Mocci, Evelina, Kundu, Prosenjit, Wheeler, William, Arslan, Alan A., Beane-Freeman, Laura E., Bracci, Paige M., Brennan, Paul, Canzian, Federico, Du, Mengmeng, Gallinger, Steven, Giles, Graham G., Goodman, Phyllis J., Kooperberg, Charles, Le Marchand, Loic, Neale, Rachel E., Shu, Xiao-Ou, Visvanathan, Kala, White, Emily, Zheng, Wei, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Bamlet, William R., Berndt, Sonja, Blackford, Amanda L., Bueno-de-Mesquita, Bas, Buring, Julie E., Campa, Daniele, Chanock, Stephen J., Childs, Erica J., Duell, Eric J., Fuchs, Charles S., Gaziano, J. Michael, Giovannucci, Edward L., Goggins, Michael G., Hartge, Patricia, Hassan, Manal M., Holly, Elizabeth A., Hoover, Robert N., Hung, Rayjean J., Kurtz, Robert C., Lee, I-Min, Malats, Nuria, Milne, Roger L., Ng, Kimmie, Oberg, Ann L., Panico, Salvatore, Peters, Ulrike, Porta, Miquel, Rabe, Kari G., Riboli, Elio, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Silverman, Debra T., Stevens, Victoria L., Strobel, Oliver, Thompson, Ian M., Tjonneland, Anne, Trichopoulou, Antonia, Van den Eeden, Stephen K., Wactawski-Wende, Jean, Wentzensen, Nicolas, Wilkens, Lynne R., Yu, Herbert, Yuan, Fangcheng, Zeleniuch-Jacquotte, Anne, Amundadottir, Laufey T., Li, Donghui, Jacobs, Eric J., Petersen, Gloria M., Wolpin, Brian M., Risch, Harvey A., Kraft, Peter, Chatterjee, Nilanjan, Klein, Alison P., and Stolzenberg-Solomon, Rachael
Abstract: Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 similar to 10(-8) was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P-interaction = 3.08 x 10(-9)). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r(2) = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings.Significance: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
Published: 2021

13. Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3

Author: Mocci, Evelina, primary, Kundu, Prosenjit, additional, Wheeler, William, additional, Arslan, Alan A., additional, Beane-Freeman, Laura E., additional, Bracci, Paige M., additional, Brennan, Paul, additional, Canzian, Federico, additional, Du, Mengmeng, additional, Gallinger, Steven, additional, Giles, Graham G., additional, Goodman, Phyllis J., additional, Kooperberg, Charles, additional, Le Marchand, Loic, additional, Neale, Rachel E., additional, Shu, Xiao-Ou, additional, Visvanathan, Kala, additional, White, Emily, additional, Zheng, Wei, additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Babic, Ana, additional, Bamlet, William R., additional, Berndt, Sonja I., additional, Blackford, Amanda L., additional, Bueno-de-Mesquita, Bas, additional, Buring, Julie E., additional, Campa, Daniele, additional, Chanock, Stephen J., additional, Childs, Erica J., additional, Duell, Eric J., additional, Fuchs, Charles S., additional, Gaziano, J. Michael, additional, Giovannucci, Edward L., additional, Goggins, Michael G., additional, Hartge, Patricia, additional, Hassan, Manal M., additional, Holly, Elizabeth A., additional, Hoover, Robert N., additional, Hung, Rayjean J., additional, Kurtz, Robert C., additional, Lee, I-Min, additional, Malats, Núria, additional, Milne, Roger L., additional, Ng, Kimmie, additional, Oberg, Ann L., additional, Panico, Salvatore, additional, Peters, Ulrike, additional, Porta, Miquel, additional, Rabe, Kari G., additional, Riboli, Elio, additional, Rothman, Nathaniel, additional, Scelo, Ghislaine, additional, Sesso, Howard D., additional, Silverman, Debra T., additional, Stevens, Victoria L., additional, Strobel, Oliver, additional, Thompson, Ian M., additional, Tjonneland, Anne, additional, Trichopoulou, Antonia, additional, Van Den Eeden, Stephen K., additional, Wactawski-Wende, Jean, additional, Wentzensen, Nicolas, additional, Wilkens, Lynne R., additional, Yu, Herbert, additional, Yuan, Fangcheng, additional, Zeleniuch-Jacquotte, Anne, additional, Amundadottir, Laufey T., additional, Li, Donghui, additional, Jacobs, Eric J., additional, Petersen, Gloria M., additional, Wolpin, Brian M., additional, Risch, Harvey A., additional, Kraft, Peter, additional, Chatterjee, Nilanjan, additional, Klein, Alison P., additional, and Stolzenberg-Solomon, Rachael, additional
Published: 2021
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14. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Author: Zhong, Jun, primary, Jermusyk, Ashley, additional, Wu, Lang, additional, Hoskins, Jason W, additional, Collins, Irene, additional, Mocci, Evelina, additional, Zhang, Mingfeng, additional, Song, Lei, additional, Chung, Charles C, additional, Zhang, Tongwu, additional, Xiao, Wenming, additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Arslan, Alan A, additional, Babic, Ana, additional, Bamlet, William R, additional, Beane-Freeman, Laura, additional, Berndt, Sonja, additional, Borgida, Ayelet, additional, Bracci, Paige M, additional, Brais, Lauren, additional, Brennan, Paul, additional, Bueno-de-Mesquita, Bas, additional, Buring, Julie, additional, Canzian, Federico, additional, Childs, Erica J, additional, Cotterchio, Michelle, additional, Du, Mengmeng, additional, Duell, Eric J, additional, Fuchs, Charles, additional, Gallinger, Steven, additional, Gaziano, J Michael, additional, Giles, Graham G, additional, Giovannucci, Edward, additional, Goggins, Michael, additional, Goodman, Gary E, additional, Goodman, Phyllis J, additional, Haiman, Christopher, additional, Hartge, Patricia, additional, Hasan, Manal, additional, Helzlsouer, Kathy J, additional, Holly, Elizabeth A, additional, Klein, Eric A, additional, Kogevinas, Manolis, additional, Kurtz, Robert J, additional, LeMarchand, Loic, additional, Malats, Núria, additional, Männistö, Satu, additional, Milne, Roger, additional, Neale, Rachel E, additional, Ng, Kimmie, additional, Obazee, Ofure, additional, Oberg, Ann L, additional, Orlow, Irene, additional, Patel, Alpa V, additional, Peters, Ulrike, additional, Porta, Miquel, additional, Rothman, Nathaniel, additional, Scelo, Ghislaine, additional, Sesso, Howard D, additional, Severi, Gianluca, additional, Sieri, Sabina, additional, Silverman, Debra, additional, Sund, Malin, additional, Tjønneland, Anne, additional, Thornquist, Mark D, additional, Tobias, Geoffrey S, additional, Trichopoulou, Antonia, additional, Van Den Eeden, Stephen K, additional, Visvanathan, Kala, additional, Wactawski-Wende, Jean, additional, Wentzensen, Nicolas, additional, White, Emily, additional, Yu, Herbert, additional, Yuan, Chen, additional, Zeleniuch-Jacquotte, Anne, additional, Hoover, Robert, additional, Brown, Kevin, additional, Kooperberg, Charles, additional, Risch, Harvey A, additional, Jacobs, Eric J, additional, Li, Donghui, additional, Yu, Kai, additional, Shu, Xiao-Ou, additional, Chanock, Stephen J, additional, Wolpin, Brian M, additional, Stolzenberg-Solomon, Rachael Z, additional, Chatterjee, Nilanjan, additional, Klein, Alison P, additional, Smith, Jill P, additional, Kraft, Peter, additional, Shi, Jianxin, additional, Petersen, Gloria M, additional, Zheng, Wei, additional, and Amundadottir, Laufey T, additional
Published: 2020
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15. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer

Author: Zhong, Jun, Jermusyk, Ashley, Wu, Lang, Hoskins, Jason W., Collins, Irene, Mocci, Evelina, Zhang, Mingfeng, Song, Lei, Chung, Charles C., Zhang, Tongwu, Xiao, Wenming, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie, Canzian, Federico, Childs, Erica J., Cotterchio, Michelle, Du, Mengmeng, Duell, Eric J., Fuchs, Charles, Gallinger, Steven, Gaziano, J. Michael, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A., Kogevinas, Manolis, Kurtz, Robert J., LeMarchand, Loic, Malats, Nuria, Mannisto, Satu, Milne, Roger, Neale, Rachel E., Ng, Kimmie, Obazee, Ofure, Oberg, Ann L., Orlow, Irene, Patel, Alpa, V, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Sieri, Sabina, Silverman, Debra, Sund, Malin, Tjonneland, Anne, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulou, Antonia, Van den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yuan, Chen, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Brown, Kevin, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Yu, Kai, Shu, Xiao-Ou, Chanock, Stephen J., Wolpin, Brian M., Stolzenberg-Solomon, Rachael Z., Chatterjee, Nilanjan, Klein, Alison P., Smith, Jill P., Kraft, Peter, Shi, Jianxin, Petersen, Gloria M., Zheng, Wei, Amundadottir, Laufey T., Zhong, Jun, Jermusyk, Ashley, Wu, Lang, Hoskins, Jason W., Collins, Irene, Mocci, Evelina, Zhang, Mingfeng, Song, Lei, Chung, Charles C., Zhang, Tongwu, Xiao, Wenming, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Bueno-de-Mesquita, Bas, Buring, Julie, Canzian, Federico, Childs, Erica J., Cotterchio, Michelle, Du, Mengmeng, Duell, Eric J., Fuchs, Charles, Gallinger, Steven, Gaziano, J. Michael, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Holly, Elizabeth A., Klein, Eric A., Kogevinas, Manolis, Kurtz, Robert J., LeMarchand, Loic, Malats, Nuria, Mannisto, Satu, Milne, Roger, Neale, Rachel E., Ng, Kimmie, Obazee, Ofure, Oberg, Ann L., Orlow, Irene, Patel, Alpa, V, Peters, Ulrike, Porta, Miquel, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Sieri, Sabina, Silverman, Debra, Sund, Malin, Tjonneland, Anne, Thornquist, Mark D., Tobias, Geoffrey S., Trichopoulou, Antonia, Van den Eeden, Stephen K., Visvanathan, Kala, Wactawski-Wende, Jean, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yuan, Chen, Zeleniuch-Jacquotte, Anne, Hoover, Robert, Brown, Kevin, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Yu, Kai, Shu, Xiao-Ou, Chanock, Stephen J., Wolpin, Brian M., Stolzenberg-Solomon, Rachael Z., Chatterjee, Nilanjan, Klein, Alison P., Smith, Jill P., Kraft, Peter, Shi, Jianxin, Petersen, Gloria M., Zheng, Wei, and Amundadottir, Laufey T.
Abstract: Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples). Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEPI) and 11 at six known risk loci (5p15.33: TERT, CLPTMIL, ZDHHCIIB; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTMIL, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction. Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
Published: 2020
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16. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

Author: Bailey-Wilson Joan E, Childs Erica J, Cropp Cheryl D, Schaid Daniel J, Xu Jianfeng, Camp Nicola J, Cannon-Albright Lisa A, Farnham James M, George Asha, Powell Isaac, Carpten John D, Giles Graham G, Hopper John L, Severi Gianluca, English Dallas R, Foulkes William D, Mæhle Lovise, Møller Pål, Eeles Rosalind, Easton Douglas, Guy Michelle, Edwards Steve, Badzioch Michael D, Whittemore Alice S, Oakley-Girvan Ingrid, Hsieh Chih-Lin, Dimitrov Latchezar, Stanford Janet L, Karyadi Danielle M, Deutsch Kerry, McIntosh Laura, Ostrander Elaine A, Wiley Kathleen E, Isaacs Sarah D, Walsh Patrick C, Thibodeau Stephen N, McDonnell Shannon K, Hebbring Scott, Lange Ethan M, Cooney Kathleen A, Tammela Teuvo LJ, Schleutker Johanna, Maier Christiane, Bochum Sylvia, Hoegel Josef, Grönberg Henrik, Wiklund Fredrik, Emanuelsson Monica, Cancel-Tassin Geraldine, Valeri Antoine, Cussenot Olivier, and Isaacs William B
Subjects: Internal medicine, RC31-1245, Genetics, QH426-470
Abstract: Abstract Background Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2–3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2–3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
Published: 2012
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17. Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Author: Walsh, Naomi, Zhang, Han, Hyland, Paula L, Yang, Qi, Mocci, Evelina, Zhang, Mingfeng, Childs, Erica J, Collins, Irene, Wang, Zhaoming, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Brennan, Paul, Canzian, Federico, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goggins, Michael, Goodman, Gary E, Goodman, Phyllis J, Hung, Rayjean J, Kooperberg, Charles, Kurtz, Robert C, Malats, Núria, LeMarchand, Loic, Neale, Rachel E, Olson, Sara H, Scelo, Ghislaine, Shu, Xiao O, Van Den Eeden, Stephen K, Visvanathan, Kala, White, Emily, Zheng, Wei, PanScan and PanC4 consortia, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Bamlet, William R, Berndt, Sonja I, Borgida, Ayelet, Boutron-Ruault, Marie-Christine, Brais, Lauren, Bueno-de-Mesquita, Bas, Buring, Julie, Chaffee, Kari G, Chanock, Stephen, Cleary, Sean, Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, M Gaziano, J Michael, Giovannucci, Edward, Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J, Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert, Janout, Vladimir, Klein, Eric A, Laheru, Daniel, Lee, I-Min, Lu, Lingeng, Mannisto, Satu, Milne, Roger L, Oberg, Ann L, Orlow, Irene, Patel, Alpa V, Peters, Ulrike, Porta, Miquel, Real, Francisco X, Rothman, Nathaniel, Sesso, Howard D, Severi, Gianluca, Silverman, Debra, Strobel, Oliver, Sund, Malin, Thornquist, Mark D, Tobias, Geoffrey S, Wactawski-Wende, Jean, Wareham, Nick, Weiderpass, Elisabete, Wentzensen, Nicolas, Wheeler, William, Yu, Herbert, Zeleniuch-Jacquotte, Anne, Kraft, Peter, Li, Donghui, Jacobs, Eric J, Petersen, Gloria M, Wolpin, Brian M, Risch, Harvey A, Amundadottir, Laufey T, Yu, Kai, Klein, Alison P, Stolzenberg-Solomon, Rachael Z, Wareham, Nicholas [0000-0003-1422-2993], and Apollo - University of Cambridge Repository
Subjects: Pancreatic Neoplasms, Models, Statistical, Case-Control Studies, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study
Abstract: Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
Published: 2018

18. Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study

Author: Chen, Fei, primary, Childs, Erica J., additional, Mocci, Evelina, additional, Bracci, Paige, additional, Gallinger, Steven, additional, Li, Donghui, additional, Neale, Rachel E., additional, Olson, Sara H., additional, Scelo, Ghislaine, additional, Bamlet, William R., additional, Blackford, Amanda L., additional, Borges, Michael, additional, Brennan, Paul, additional, Chaffee, Kari G., additional, Duggal, Priya, additional, Hassan, Manal J., additional, Holly, Elizabeth A., additional, Hung, Rayjean J., additional, Goggins, Michael G., additional, Kurtz, Robert C., additional, Oberg, Ann L., additional, Orlow, Irene, additional, Yu, Herbert, additional, Petersen, Gloria M., additional, Risch, Harvey A., additional, and Klein, Alison P., additional
Published: 2019
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19. Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Author: Walsh, Naomi, Zhang, Han, Hyland, Paula L., Yang, Qi, Mocci, Evelina, Zhang, Mingfeng, Childs, Erica J., Collins, Irene, Wang, Zhaoming, Arslan, Alan A., Beane-Freeman, Laura, Bracci, Paige M., Brennan, Paul, Canzian, Federico, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hung, Rayjean J., Kooperberg, Charles, Kurtz, Robert C., Malats, Núria, LeMarchand, Loic, Neale, Rachel E., Olson, Sara H., Scelo, Ghislaine, Shu, Xiao O., Van Den Eeden, Stephen K., Visvanathan, Kala, White, Emily, Zheng, Wei, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Bamlet, William R., Berndt, Sonja I., Borgida, Ayelet, Boutron-Ruault, Marie-Christine, Brais, Lauren, Bueno-de-Mesquita, Bas, Buring, Julie, Chaffee, Kari G., Chanock, Stephen, Cleary, Sean, Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, M. Gaziano, J. Michael, Giovannucci, Edward, Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Janout, Vladimir, Klein, Eric A., Laheru, Daniel, Lee, I-Min, Lu, Lingeng, Mannisto, Satu, Milne, Roger L., Oberg, Ann L., Orlow, Irene, Patel, Alpa V., Peters, Ulrike, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Sesso, Howard D., Severi, Gianluca, Silverman, Debra, Strobel, Oliver, Sund, Malin, Thornquist, Mark D., Tobias, Geoffrey S., Wactawski-Wende, Jean, Wareham, Nick, Weiderpass, Elisabete, Wentzensen, Nicolas, Wheeler, William, Yu, Herbert, Zeleniuch-Jacquotte, Anne, Kraft, Peter, Li, Donghui, Jacobs, Eric J., Petersen, Gloria M., Wolpin, Brian M., Risch, Harvey A., Amundadottir, Laufey T., Yu, Kai, Klein, Alison P., Stolzenberg-Solomon, Rachael Z., Walsh, Naomi, Zhang, Han, Hyland, Paula L., Yang, Qi, Mocci, Evelina, Zhang, Mingfeng, Childs, Erica J., Collins, Irene, Wang, Zhaoming, Arslan, Alan A., Beane-Freeman, Laura, Bracci, Paige M., Brennan, Paul, Canzian, Federico, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hung, Rayjean J., Kooperberg, Charles, Kurtz, Robert C., Malats, Núria, LeMarchand, Loic, Neale, Rachel E., Olson, Sara H., Scelo, Ghislaine, Shu, Xiao O., Van Den Eeden, Stephen K., Visvanathan, Kala, White, Emily, Zheng, Wei, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Bamlet, William R., Berndt, Sonja I., Borgida, Ayelet, Boutron-Ruault, Marie-Christine, Brais, Lauren, Bueno-de-Mesquita, Bas, Buring, Julie, Chaffee, Kari G., Chanock, Stephen, Cleary, Sean, Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, M. Gaziano, J. Michael, Giovannucci, Edward, Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Janout, Vladimir, Klein, Eric A., Laheru, Daniel, Lee, I-Min, Lu, Lingeng, Mannisto, Satu, Milne, Roger L., Oberg, Ann L., Orlow, Irene, Patel, Alpa V., Peters, Ulrike, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Sesso, Howard D., Severi, Gianluca, Silverman, Debra, Strobel, Oliver, Sund, Malin, Thornquist, Mark D., Tobias, Geoffrey S., Wactawski-Wende, Jean, Wareham, Nick, Weiderpass, Elisabete, Wentzensen, Nicolas, Wheeler, William, Yu, Herbert, Zeleniuch-Jacquotte, Anne, Kraft, Peter, Li, Donghui, Jacobs, Eric J., Petersen, Gloria M., Wolpin, Brian M., Risch, Harvey A., Amundadottir, Laufey T., Yu, Kai, Klein, Alison P., and Stolzenberg-Solomon, Rachael Z.
Abstract: Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
Published: 2019
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20. Abstract 242: Large pathway and gene set analysis of GWAS data identifies novel associations for pancreatic cancer

Author: Walsh, Naomi, primary, Zhang, Han, additional, Hyland, Paula L., additional, Yang, Qi, additional, Mocci, Evelina, additional, Zhang, Mingfeng, additional, Childs, Erica J., additional, Wang, Zhaoming, additional, Chanock, Stephen, additional, Hartge, Patricia, additional, Hoover, Robert, additional, Kraft, Peter, additional, Li, Donghui, additional, Jacobs, Eric J., additional, Petersen, Gloria M., additional, Wolpin, Brian M., additional, Risch, Harvey A., additional, Amundadottir, Laufey T., additional, Yu, Kai, additional, Klein, Alison P., additional, and Stolzenberg-Solomon, Rachael Z., additional
Published: 2018
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21. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: Klein, Alison P., primary, Wolpin, Brian M., additional, Risch, Harvey A., additional, Stolzenberg-Solomon, Rachael Z., additional, Mocci, Evelina, additional, Zhang, Mingfeng, additional, Canzian, Federico, additional, Childs, Erica J., additional, Hoskins, Jason W., additional, Jermusyk, Ashley, additional, Zhong, Jun, additional, Chen, Fei, additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Arslan, Alan A., additional, Babic, Ana, additional, Bamlet, William R., additional, Beane-Freeman, Laura, additional, Berndt, Sonja I., additional, Blackford, Amanda, additional, Borges, Michael, additional, Borgida, Ayelet, additional, Bracci, Paige M., additional, Brais, Lauren, additional, Brennan, Paul, additional, Brenner, Hermann, additional, Bueno-de-Mesquita, Bas, additional, Buring, Julie, additional, Campa, Daniele, additional, Capurso, Gabriele, additional, Cavestro, Giulia Martina, additional, Chaffee, Kari G., additional, Chung, Charles C., additional, Cleary, Sean, additional, Cotterchio, Michelle, additional, Dijk, Frederike, additional, Duell, Eric J., additional, Foretova, Lenka, additional, Fuchs, Charles, additional, Funel, Niccola, additional, Gallinger, Steven, additional, M. Gaziano, J. Michael, additional, Gazouli, Maria, additional, Giles, Graham G., additional, Giovannucci, Edward, additional, Goggins, Michael, additional, Goodman, Gary E., additional, Goodman, Phyllis J., additional, Hackert, Thilo, additional, Haiman, Christopher, additional, Hartge, Patricia, additional, Hasan, Manal, additional, Hegyi, Peter, additional, Helzlsouer, Kathy J., additional, Herman, Joseph, additional, Holcatova, Ivana, additional, Holly, Elizabeth A., additional, Hoover, Robert, additional, Hung, Rayjean J., additional, Jacobs, Eric J., additional, Jamroziak, Krzysztof, additional, Janout, Vladimir, additional, Kaaks, Rudolf, additional, Khaw, Kay-Tee, additional, Klein, Eric A., additional, Kogevinas, Manolis, additional, Kooperberg, Charles, additional, Kulke, Matthew H., additional, Kupcinskas, Juozas, additional, Kurtz, Robert J., additional, Laheru, Daniel, additional, Landi, Stefano, additional, Lawlor, Rita T., additional, Lee, I.-Min, additional, LeMarchand, Loic, additional, Lu, Lingeng, additional, Malats, Núria, additional, Mambrini, Andrea, additional, Mannisto, Satu, additional, Milne, Roger L., additional, Mohelníková-Duchoňová, Beatrice, additional, Neale, Rachel E., additional, Neoptolemos, John P., additional, Oberg, Ann L., additional, Olson, Sara H., additional, Orlow, Irene, additional, Pasquali, Claudio, additional, Patel, Alpa V., additional, Peters, Ulrike, additional, Pezzilli, Raffaele, additional, Porta, Miquel, additional, Real, Francisco X., additional, Rothman, Nathaniel, additional, Scelo, Ghislaine, additional, Sesso, Howard D., additional, Severi, Gianluca, additional, Shu, Xiao-Ou, additional, Silverman, Debra, additional, Smith, Jill P., additional, Soucek, Pavel, additional, Sund, Malin, additional, Talar-Wojnarowska, Renata, additional, Tavano, Francesca, additional, Thornquist, Mark D., additional, Tobias, Geoffrey S., additional, Van Den Eeden, Stephen K., additional, Vashist, Yogesh, additional, Visvanathan, Kala, additional, Vodicka, Pavel, additional, Wactawski-Wende, Jean, additional, Wang, Zhaoming, additional, Wentzensen, Nicolas, additional, White, Emily, additional, Yu, Herbert, additional, Yu, Kai, additional, Zeleniuch-Jacquotte, Anne, additional, Zheng, Wei, additional, Kraft, Peter, additional, Li, Donghui, additional, Chanock, Stephen, additional, Obazee, Ofure, additional, Petersen, Gloria M., additional, and Amundadottir, Laufey T., additional
Published: 2018
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22. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-de-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, LeMarchand, Loic, Lu, Lingeng, Malats, Nuria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelnikova-Duchonova, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., Amundadottir, Laufey T., Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-de-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, LeMarchand, Loic, Lu, Lingeng, Malats, Nuria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelnikova-Duchonova, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.
Abstract: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.
Published: 2018
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23. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: MS MDL 1, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., Amundadottir, Laufey T., MS MDL 1, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay Tee, Klein, Eric A., Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H., Kupcinskas, Juozas, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.
Published: 2018

24. Analysis of Heritability and Genetic Architecture of Pancreatic Cancer: A PanC4 Study.

Author: Fei Chen, Childs, Erica J., Mocci, Evelina, Bracci, Paige, Gallinger, Steven, Donghui Li, Neale, Rachel E., Olson, Sara H., Scelo, Ghislaine, Bamlet, William R., Blackford, Amanda L., Borges, Michael, Brennan, Paul, Chaffee, Kari G., Duggal, Priya, Hassan, Manal J., Holly, Elizabeth A., Hung, Rayjean J., Goggins, Michael G., and Kurtz, Robert C.
Abstract: Background: Pancreatic cancer is the fourth-leading cause of cancer death in both men and women in the United States. The currently identified common susceptibility loci account for a small fraction of estimated heritability. We sought to estimate overall heritability of pancreatic cancer and partition the heritability by variant frequencies and functional annotations. Methods: Analysis using the genome-based restricted maximum likelihood method (GREML) was conducted on Pancreatic Cancer Case-Control Consortium (PanC4) genome-wide association study (GWAS) data from 3,568 pancreatic cancer cases and 3,363 controls of European Ancestry. Results: Applying linkage disequilibrium- and minor allele frequency-stratified GREML (GREML-LDMS) method to imputed GWAS data, we estimated the overall heritability of pancreatic cancer to be 21.2% (SE = 4.8%). Across the functional groups (intronic, intergenic, coding, and regulatory variants), intronic variants account for most of the estimated heritability (12.4%). Previously identified GWAS loci explained 4.1% of the total phenotypic variation of pancreatic cancer. Mutations in hereditary pancreatic cancer susceptibility genes are present in 4% to 10% of patients with pancreatic cancer, yet our GREML-LDMS results suggested these regions explain only 0.4% of total phenotypic variance for pancreatic cancer. Conclusions: Although higher than previous studies, our estimated 21.2% overall heritability may still be downwardly biased due to the inherent limitation that the contribution of rare variants in genes with a substantive overall impact on disease are not captured when applying these commonly used methods to imputed GWAS data. Impact: Our work demonstrated the importance of rare and common variants in pancreatic cancer risk. [ABSTRACT FROM AUTHOR]
Published: 2019
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25. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J., Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C., Hautman, Christopher, Arslan, Alan A., Beane-Freeman, Laura, Bracci, Paige M., Buring, Julie, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goodman, Gary E., Goodman, Phyllis J., Kamineni, Aruna, Kolonel, Laurence N., Kulke, Matthew H., Malats, Nuria, Olson, Sara H., Sesso, Howard D., Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C., Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H. Bas, Basso, Daniela, Berndt, Sonja I., Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F., Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E., Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L., Goggins, Michael, Gross, Myron, Haiman, Christopher A., Hassan, Manal, Helzlsouer, Kathy J., Hu, Nan, Hunter, David J., Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C., Landi, Maria T., Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Neale, Rachel E., Oberg, Ann L., Panico, Salvatore, Patel, Alpa V., Peeters, Petra H. M., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Ramon Quiros, J., Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T., Soucek, Pavel, Strobel, Oliver, Sund, Malin, Malecka-Panas, Ewa, Taylor, Philip R., Tavano, Francesca, Travis, Ruth C., Thornquist, Mark, Tjonneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J., Petersen, Gloria M., Stolzenberg-Solomon, Rachael S., Wolpin, Brian M., Kraft, Peter, Klein, Alison P., Canzian, Federico, Amundadottir, Laufey T., Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J., Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C., Hautman, Christopher, Arslan, Alan A., Beane-Freeman, Laura, Bracci, Paige M., Buring, Julie, Duell, Eric J., Gallinger, Steven, Giles, Graham G., Goodman, Gary E., Goodman, Phyllis J., Kamineni, Aruna, Kolonel, Laurence N., Kulke, Matthew H., Malats, Nuria, Olson, Sara H., Sesso, Howard D., Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C., Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H. Bas, Basso, Daniela, Berndt, Sonja I., Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F., Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E., Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L., Goggins, Michael, Gross, Myron, Haiman, Christopher A., Hassan, Manal, Helzlsouer, Kathy J., Hu, Nan, Hunter, David J., Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J., Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C., Landi, Maria T., Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Neale, Rachel E., Oberg, Ann L., Panico, Salvatore, Patel, Alpa V., Peeters, Petra H. M., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Ramon Quiros, J., Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T., Soucek, Pavel, Strobel, Oliver, Sund, Malin, Malecka-Panas, Ewa, Taylor, Philip R., Tavano, Francesca, Travis, Ruth C., Thornquist, Mark, Tjonneland, Anne, Tobias, Geoffrey S., Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A., Jacobs, Eric J., Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J., Petersen, Gloria M., Stolzenberg-Solomon, Rachael S., Wolpin, Brian M., Kraft, Peter, Klein, Alison P., Canzian, Federico, and Amundadottir, Laufey T.
Abstract: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10(-15)), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10(-9)) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10(-8)). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L-TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10(-8)). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10(-4)-2.0x10(-3)). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
Published: 2016
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26. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H Bas, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka-Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg-Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T, MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-de-Mesquita, H Bas, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka-Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg-Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, and Amundadottir, Laufey T
Published: 2016

27. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: Zhang, Mingfeng, primary, Wang, Zhaoming, additional, Obazee, Ofure, additional, Jia, Jinping, additional, Childs, Erica J., additional, Hoskins, Jason, additional, Figlioli, Gisella, additional, Mocci, Evelina, additional, Collins, Irene, additional, Chung, Charles C., additional, Hautman, Christopher, additional, Arslan, Alan A., additional, Beane-Freeman, Laura, additional, Bracci, Paige M., additional, Buring, Julie, additional, Duell, Eric J., additional, Gallinger, Steven, additional, Giles, Graham G., additional, Goodman, Gary E., additional, Goodman, Phyllis J., additional, Kamineni, Aruna, additional, Kolonel, Laurence N., additional, Kulke, Matthew H., additional, Malats, Núria, additional, Olson, Sara H., additional, Sesso, Howard D., additional, Visvanathan, Kala, additional, White, Emily, additional, Zheng, Wei, additional, Abnet, Christian C., additional, Albanes, Demetrius, additional, Andreotti, Gabriella, additional, Brais, Lauren, additional, Bueno-de-Mesquita, H. Bas, additional, Basso, Daniela, additional, Berndt, Sonja I., additional, Boutron-Ruault, Marie-Christine, additional, Bijlsma, Maarten F., additional, Brenner, Hermann, additional, Burdette, Laurie, additional, Campa, Daniele, additional, Caporaso, Neil E., additional, Capurso, Gabriele, additional, Cavestro, Giulia Martina, additional, Cotterchio, Michelle, additional, Costello, Eithne, additional, Elena, Joanne, additional, Boggi, Ugo, additional, Gaziano, J. Michael, additional, Gazouli, Maria, additional, Giovannucci, Edward L., additional, Goggins, Michael, additional, Gross, Myron, additional, Haiman, Christopher A., additional, Hassan, Manal, additional, Helzlsouer, Kathy J., additional, Hu, Nan, additional, Hunter, David J., additional, Iskierka-Jazdzewska, Elzbieta, additional, Jenab, Mazda, additional, Kaaks, Rudolf, additional, Key, Timothy J., additional, Khaw, Kay-Tee, additional, Klein, Eric A., additional, Kogevinas, Manolis, additional, Krogh, Vittorio, additional, Kupcinskas, Juozas, additional, Kurtz, Robert C., additional, Landi, Maria T., additional, Landi, Stefano, additional, Le Marchand, Loic, additional, Mambrini, Andrea, additional, Mannisto, Satu, additional, Milne, Roger L., additional, Neale, Rachel E., additional, Oberg, Ann L., additional, Panico, Salvatore, additional, Patel, Alpa V., additional, Peeters, Petra H. M., additional, Peters, Ulrike, additional, Pezzilli, Raffaele, additional, Porta, Miquel, additional, Purdue, Mark, additional, Quiros, J. Ramón, additional, Riboli, Elio, additional, Rothman, Nathaniel, additional, Scarpa, Aldo, additional, Scelo, Ghislaine, additional, Shu, Xiao-Ou, additional, Silverman, Debra T., additional, Soucek, Pavel, additional, Strobel, Oliver, additional, Sund, Malin, additional, Małecka-Panas, Ewa, additional, Taylor, Philip R., additional, Tavano, Francesca, additional, Travis, Ruth C., additional, Thornquist, Mark, additional, Tjønneland, Anne, additional, Tobias, Geoffrey S., additional, Trichopoulos, Dimitrios, additional, Vashist, Yogesh, additional, Vodicka, Pavel, additional, Wactawski-Wende, Jean, additional, Wentzensen, Nicolas, additional, Yu, Herbert, additional, Yu, Kai, additional, Zeleniuch-Jacquotte, Anne, additional, Kooperberg, Charles, additional, Risch, Harvey A., additional, Jacobs, Eric J., additional, Li, Donghui, additional, Fuchs, Charles, additional, Hoover, Robert, additional, Hartge, Patricia, additional, Chanock, Stephen J., additional, Petersen, Gloria M., additional, Stolzenberg-Solomon, Rachael S., additional, Wolpin, Brian M., additional, Kraft, Peter, additional, Klein, Alison P., additional, Canzian, Federico, additional, and Amundadottir, Laufey T., additional
Published: 2016
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28. Association of Common Susceptibility Variants of Pancreatic Cancer in Higher-Risk Patients: A PACGENE Study

Author: Childs, Erica J., primary, Chaffee, Kari G., additional, Gallinger, Steven, additional, Syngal, Sapna, additional, Schwartz, Ann G., additional, Cote, Michele L., additional, Bondy, Melissa L., additional, Hruban, Ralph H., additional, Chanock, Stephen J., additional, Hoover, Robert N., additional, Fuchs, Charles S., additional, Rider, David N., additional, Amundadottir, Laufey T., additional, Stolzenberg-Solomon, Rachael, additional, Wolpin, Brian M., additional, Risch, Harvey A., additional, Goggins, Michael G., additional, Petersen, Gloria M., additional, and Klein, Alison P., additional
Published: 2016
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29. Whole Genome Sequencing Defines the Genetic Heterogeneity of Familial Pancreatic Cancer

Author: Roberts, Nicholas J., primary, Norris, Alexis L., additional, Petersen, Gloria M., additional, Bondy, Melissa L., additional, Brand, Randall, additional, Gallinger, Steven, additional, Kurtz, Robert C., additional, Olson, Sara H., additional, Rustgi, Anil K., additional, Schwartz, Ann G., additional, Stoffel, Elena, additional, Syngal, Sapna, additional, Zogopoulos, George, additional, Ali, Syed Z., additional, Axilbund, Jennifer, additional, Chaffee, Kari G., additional, Chen, Yun-Ching, additional, Cote, Michele L., additional, Childs, Erica J., additional, Douville, Christopher, additional, Goes, Fernando S., additional, Herman, Joseph M., additional, Iacobuzio-Donahue, Christine, additional, Kramer, Melissa, additional, Makohon-Moore, Alvin, additional, McCombie, Richard W., additional, McMahon, K. Wyatt, additional, Niknafs, Noushin, additional, Parla, Jennifer, additional, Pirooznia, Mehdi, additional, Potash, James B., additional, Rhim, Andrew D., additional, Smith, Alyssa L., additional, Wang, Yuxuan, additional, Wolfgang, Christopher L., additional, Wood, Laura D., additional, Zandi, Peter P., additional, Goggins, Michael, additional, Karchin, Rachel, additional, Eshleman, James R., additional, Papadopoulos, Nickolas, additional, Kinzler, Kenneth W., additional, Vogelstein, Bert, additional, Hruban, Ralph H., additional, and Klein, Alison P., additional
Published: 2016
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30. Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families

Author: Bailey-Wilson, Joan E, Childs, Erica J, Cropp, Cheryl D, Schaid, Daniel J, Xu, Jianfeng, Camp, Nicola J, Cannon-Albright, Lisa A, Farnham, James M, George, Asha, Powell, Isaac, Carpten, John D, Giles, Graham G, Hopper, John L, Severi, Gianluca, English, Dallas R, Foulkes, William D, Mæhle, Lovise, Møller, Pål, Eeles, Rosalind, Easton, Douglas, Guy, Michelle, Edwards, Steve, Badzioch, Michael D, Whittemore, Alice S, Oakley-Girvan, Ingrid, Hsieh, Chih-Lin, Dimitrov, Latchezar, Stanford, Janet L, Karyadi, Danielle M, Deutsch, Kerry, McIntosh, Laura, Ostrander, Elaine A, Wiley, Kathleen E, Isaacs, Sarah D, Walsh, Patrick C, Thibodeau, Stephen N, McDonnell, Shannon K, Hebbring, Scott, Lange, Ethan M, Cooney, Kathleen A, Tammela, Teuvo LJ, Schleutker, Johanna, Maier, Christiane, Bochum, Sylvia, Hoegel, Josef, Grönberg, Henrik, Wiklund, Fredrik, Emanuelsson, Monica, Cancel-Tassin, Geraldine, Valeri, Antoine, Cussenot, Olivier, Isaacs, William B, International Consortium for Prostate Cancer Genetics, Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
Subjects: Male, Chromosomes, Human, X, Genetic Linkage, Humans, Prostatic Neoplasms, Alleles, Genome-Wide Association Study, Microsatellite Repeats
Abstract: BACKGROUND: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. METHODS: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. RESULTS: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. CONCLUSIONS: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.
Published: 2012

31. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Author: Childs, Erica J, Mocci, Evelina, Campa, Daniele, Bracci, Paige M, Gallinger, Steven, Goggins, Michael, Li, Donghui, Neale, Rachel E, Olson, Sara H, Scelo, Ghislaine, Amundadottir, Laufey T, Bamlet, William R., Bijlsma, Maarten F, Blackford, Amanda, Borges, Michael, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, H. Bas, Canzian, Federico, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chanock, Stephen J., Cleary, Sean P., Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gazouli, Maria, Hassan, Manal, Herman, Joseph M., Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert N., Hung, Rayjean J., Janout, Vladimir, Key, Timothy J., Kupcinskas, Juozas, Kurtz, Robert C, Landi, Stefano, Lu, Lingeng, Malecka-Panas, Ewa, Mambrini, Andrea, Mohelnikova-Duchonova, Beatrice, Neoptolemos, John P., Oberg, Ann L, Orlow, Irene, Pasquali, Claudio, Pezzilli, Raffaele, Rizzato, Cosmeri, Saldia, Amethyst, Scarpa, Aldo, Stolzenberg-Solomon, Rachael Z., Strobel, Oliver, Tavano, Francesca, Vashist, Yogesh K., Vodicka, Pavel, Wolpin, Brian M, Yu, Herbert, Petersen, Gloria M, Risch, Harvey A., Klein, Alison P, Childs, Erica J, Mocci, Evelina, Campa, Daniele, Bracci, Paige M, Gallinger, Steven, Goggins, Michael, Li, Donghui, Neale, Rachel E, Olson, Sara H, Scelo, Ghislaine, Amundadottir, Laufey T, Bamlet, William R., Bijlsma, Maarten F, Blackford, Amanda, Borges, Michael, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, H. Bas, Canzian, Federico, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chanock, Stephen J., Cleary, Sean P., Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gazouli, Maria, Hassan, Manal, Herman, Joseph M., Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert N., Hung, Rayjean J., Janout, Vladimir, Key, Timothy J., Kupcinskas, Juozas, Kurtz, Robert C, Landi, Stefano, Lu, Lingeng, Malecka-Panas, Ewa, Mambrini, Andrea, Mohelnikova-Duchonova, Beatrice, Neoptolemos, John P., Oberg, Ann L, Orlow, Irene, Pasquali, Claudio, Pezzilli, Raffaele, Rizzato, Cosmeri, Saldia, Amethyst, Scarpa, Aldo, Stolzenberg-Solomon, Rachael Z., Strobel, Oliver, Tavano, Francesca, Vashist, Yogesh K., Vodicka, Pavel, Wolpin, Brian M, Yu, Herbert, Petersen, Gloria M, Risch, Harvey A., and Klein, Alison P
Published: 2015

32. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Author: MS MDL 1, Cancer, Childs, Erica J, Mocci, Evelina, Campa, Daniele, Bracci, Paige M, Gallinger, Steven, Goggins, Michael, Li, Donghui, Neale, Rachel E, Olson, Sara H, Scelo, Ghislaine, Amundadottir, Laufey T, Bamlet, William R., Bijlsma, Maarten F, Blackford, Amanda, Borges, Michael, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, H. Bas, Canzian, Federico, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chanock, Stephen J., Cleary, Sean P., Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gazouli, Maria, Hassan, Manal, Herman, Joseph M., Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert N., Hung, Rayjean J., Janout, Vladimir, Key, Timothy J., Kupcinskas, Juozas, Kurtz, Robert C, Landi, Stefano, Lu, Lingeng, Malecka-Panas, Ewa, Mambrini, Andrea, Mohelnikova-Duchonova, Beatrice, Neoptolemos, John P., Oberg, Ann L, Orlow, Irene, Pasquali, Claudio, Pezzilli, Raffaele, Rizzato, Cosmeri, Saldia, Amethyst, Scarpa, Aldo, Stolzenberg-Solomon, Rachael Z., Strobel, Oliver, Tavano, Francesca, Vashist, Yogesh K., Vodicka, Pavel, Wolpin, Brian M, Yu, Herbert, Petersen, Gloria M, Risch, Harvey A., Klein, Alison P, MS MDL 1, Cancer, Childs, Erica J, Mocci, Evelina, Campa, Daniele, Bracci, Paige M, Gallinger, Steven, Goggins, Michael, Li, Donghui, Neale, Rachel E, Olson, Sara H, Scelo, Ghislaine, Amundadottir, Laufey T, Bamlet, William R., Bijlsma, Maarten F, Blackford, Amanda, Borges, Michael, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, H. Bas, Canzian, Federico, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chanock, Stephen J., Cleary, Sean P., Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gazouli, Maria, Hassan, Manal, Herman, Joseph M., Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert N., Hung, Rayjean J., Janout, Vladimir, Key, Timothy J., Kupcinskas, Juozas, Kurtz, Robert C, Landi, Stefano, Lu, Lingeng, Malecka-Panas, Ewa, Mambrini, Andrea, Mohelnikova-Duchonova, Beatrice, Neoptolemos, John P., Oberg, Ann L, Orlow, Irene, Pasquali, Claudio, Pezzilli, Raffaele, Rizzato, Cosmeri, Saldia, Amethyst, Scarpa, Aldo, Stolzenberg-Solomon, Rachael Z., Strobel, Oliver, Tavano, Francesca, Vashist, Yogesh K., Vodicka, Pavel, Wolpin, Brian M, Yu, Herbert, Petersen, Gloria M, Risch, Harvey A., and Klein, Alison P
Published: 2015

33. Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer

Author: Childs, Erica J, primary, Mocci, Evelina, additional, Campa, Daniele, additional, Bracci, Paige M, additional, Gallinger, Steven, additional, Goggins, Michael, additional, Li, Donghui, additional, Neale, Rachel E, additional, Olson, Sara H, additional, Scelo, Ghislaine, additional, Amundadottir, Laufey T, additional, Bamlet, William R, additional, Bijlsma, Maarten F, additional, Blackford, Amanda, additional, Borges, Michael, additional, Brennan, Paul, additional, Brenner, Hermann, additional, Bueno-de-Mesquita, H Bas, additional, Canzian, Federico, additional, Capurso, Gabriele, additional, Cavestro, Giulia M, additional, Chaffee, Kari G, additional, Chanock, Stephen J, additional, Cleary, Sean P, additional, Cotterchio, Michelle, additional, Foretova, Lenka, additional, Fuchs, Charles, additional, Funel, Niccola, additional, Gazouli, Maria, additional, Hassan, Manal, additional, Herman, Joseph M, additional, Holcatova, Ivana, additional, Holly, Elizabeth A, additional, Hoover, Robert N, additional, Hung, Rayjean J, additional, Janout, Vladimir, additional, Key, Timothy J, additional, Kupcinskas, Juozas, additional, Kurtz, Robert C, additional, Landi, Stefano, additional, Lu, Lingeng, additional, Malecka-Panas, Ewa, additional, Mambrini, Andrea, additional, Mohelnikova-Duchonova, Beatrice, additional, Neoptolemos, John P, additional, Oberg, Ann L, additional, Orlow, Irene, additional, Pasquali, Claudio, additional, Pezzilli, Raffaele, additional, Rizzato, Cosmeri, additional, Saldia, Amethyst, additional, Scarpa, Aldo, additional, Stolzenberg-Solomon, Rachael Z, additional, Strobel, Oliver, additional, Tavano, Francesca, additional, Vashist, Yogesh K, additional, Vodicka, Pavel, additional, Wolpin, Brian M, additional, Yu, Herbert, additional, Petersen, Gloria M, additional, Risch, Harvey A, additional, and Klein, Alison P, additional
Published: 2015
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34. Modeling maternal-offspring gene-gene interactions: the extended-MFG test

Author: Childs, Erica J., primary, Palmer, Christina G.S., additional, Lange, Kenneth, additional, and Sinsheimer, Janet S., additional
Published: 2010
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35. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: Klein, Alison P, Wolpin, Brian M, Risch, Harvey A, Stolzenberg-Solomon, Rachael Z, Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J, Hoskins, Jason W, Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetrius, Andreotti, Gabriella, Arslan, Alan A, Babic, Ana, Bamlet, William R, Beane-Freeman, Laura, Berndt, Sonja I, Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M, Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Bas, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G, Chung, Charles C, Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J, Foretova, Lenka, Fuchs, Charles, Funel, Niccola, Gallinger, Steven, M Gaziano, J Michael, Gazouli, Maria, Giles, Graham G, Giovannucci, Edward, Goggins, Michael, Goodman, Gary E, Goodman, Phyllis J, Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J, Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert, Hung, Rayjean J, Jacobs, Eric J, Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Kooperberg, Charles, Kulke, Matthew H, Kupcinskas, Juozas, Kurtz, Robert J, Laheru, Daniel, Landi, Stefano, Lawlor, Rita T, Lee, I-Min, LeMarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Mohelníková-Duchoňová, Beatrice, Neale, Rachel E, Neoptolemos, John P, Oberg, Ann L, Olson, Sara H, Orlow, Irene, Pasquali, Claudio, Patel, Alpa V, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X, Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D, Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P, Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D, Tobias, Geoffrey S, Van Den Eeden, Stephen K, Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicolas, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M, and Amundadottir, Laufey T
Subjects: Intracellular Signaling Peptides and Proteins, Proteins, Polymorphism, Single Nucleotide, 3. Good health, Pancreatic Neoplasms, Repressor Proteins, Hepatocyte Nuclear Factor 4, Tensins, Databases, Genetic, Humans, Intercellular Signaling Peptides and Proteins, Genetic Predisposition to Disease, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study, Hepatocyte Nuclear Factor 1-beta
Abstract: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10-8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10-14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10-10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10-8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10-8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

36. Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer

Author: Walsh, Naomi, Zhang, Han, Hyland, Paula L, Yang, Qi, Mocci, Evelina, Zhang, Mingfeng, Childs, Erica J, Collins, Irene, Wang, Zhaoming, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Brennan, Paul, Canzian, Federico, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goggins, Michael, Goodman, Gary E, Goodman, Phyllis J, Hung, Rayjean J, Kooperberg, Charles, Kurtz, Robert C, Malats, Núria, LeMarchand, Loic, Neale, Rachel E, Olson, Sara H, Scelo, Ghislaine, Shu, Xiao O, Van Den Eeden, Stephen K, Visvanathan, Kala, White, Emily, Zheng, Wei, PanScan And PanC4 Consortia, Albanes, Demetrius, Andreotti, Gabriella, Babic, Ana, Bamlet, William R, Berndt, Sonja I, Borgida, Ayelet, Boutron-Ruault, Marie-Christine, Brais, Lauren, Bueno-De-Mesquita, Bas, Buring, Julie, Chaffee, Kari G, Chanock, Stephen, Cleary, Sean, Cotterchio, Michelle, Foretova, Lenka, Fuchs, Charles, M Gaziano, J Michael, Giovannucci, Edward, Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Helzlsouer, Kathy J, Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A, Hoover, Robert, Janout, Vladimir, Klein, Eric A, Laheru, Daniel, Lee, I-Min, Lu, Lingeng, Mannisto, Satu, Milne, Roger L, Oberg, Ann L, Orlow, Irene, Patel, Alpa V, Peters, Ulrike, Porta, Miquel, Real, Francisco X, Rothman, Nathaniel, Sesso, Howard D, Severi, Gianluca, Silverman, Debra, Strobel, Oliver, Sund, Malin, Thornquist, Mark D, Tobias, Geoffrey S, Wactawski-Wende, Jean, Wareham, Nick, Weiderpass, Elisabete, Wentzensen, Nicolas, Wheeler, William, Yu, Herbert, Zeleniuch-Jacquotte, Anne, Kraft, Peter, Li, Donghui, Jacobs, Eric J, Petersen, Gloria M, Wolpin, Brian M, Risch, Harvey A, Amundadottir, Laufey T, Yu, Kai, Klein, Alison P, and Stolzenberg-Solomon, Rachael Z
Subjects: Pancreatic Neoplasms, Models, Statistical, Case-Control Studies, Humans, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, 3. Good health, Carcinoma, Pancreatic Ductal, Genome-Wide Association Study
Abstract: Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets. Conclusion: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified., This work was supported by the Intramural Research Program, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health. This publication has emanated from research supported in part by a Grant from Science Foundation Ireland under Grant number [15/SIRG/3482](NW) and Health Research Board/Irish Cancer Society (CPFPR-2012–2)(NW). This work was also supported by RO1 CA154823 and federal funds from the National Cancer Institute (NCI), US National Institutes of Health, under contract number HHSN261200800001E. Please see the Supplementary Materials (available online) for a complete list of funding acknowledgments

37. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane-Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetrius, Andreotti, Gabriella, Brais, Lauren, Bueno-De-Mesquita, H Bas, Basso, Daniela, Berndt, Sonja I, Boutron-Ruault, Marie-Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka-Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay-Tee, Klein, Eric A, Kogevinas, Manolis, Krogh, Vittorio, Kupcinskas, Juozas, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra HM, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao-Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka-Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrios, Vashist, Yogesh, Vodicka, Pavel, Wactawski-Wende, Jean, Wentzensen, Nicolas, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Kooperberg, Charles, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charles, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg-Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, and Amundadottir, Laufey T
Subjects: Genotype, NR5A2, pancreatic cancer, Datasets as Topic, imputation, Polymorphism, Single Nucleotide, 3. Good health, Pancreatic Neoplasms, fine-mapping, Chromosomes, Human, Pair 1, GWAS, Chromosomes, Human, Pair 5, Humans, Genetic Predisposition to Disease, Chromosomes, Human, Pair 8, Genome-Wide Association Study
Abstract: Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.

38. Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21

Author: Anne Tjønneland, Jason W. Hoskins, Kala Visvanathan, Yogesh K. Vashist, Dimitrios Trichopoulos, Matthew H. Kulke, Ruth C. Travis, Charles S. Fuchs, Herbert Yu, Kai Yu, Phyllis J. Goodman, Michael Goggins, Jean Wactawski-Wende, Laurie Burdette, Joanne W. Elena, Andrea Mambrini, Petra H.M. Peeters, H. Bas Bueno-de-Mesquita, Maria Teresa Landi, Ulrike Peters, Mingfeng Zhang, Laurence N. Kolonel, Hermann Brenner, Elżbieta Iskierka-Jażdżewska, Robert C. Kurtz, Stephen J. Chanock, Marie-Christine Boutron-Ruault, Ann L. Oberg, Elio Riboli, Maarten F. Bijlsma, Eric J. Jacobs, Manolis Kogevinas, Evelina Mocci, Steven Gallinger, Jinping Jia, Mark P. Purdue, Raffaele Pezzilli, Harvey A. Risch, Demetrius Albanes, Irene Collins, Maria Gazouli, Michelle Cotterchio, Oliver Strobel, Erica J. Childs, Charles C. Chung, Geoffrey S. Tobias, J. Ramón Quirós, Núria Malats, Robert N. Hoover, Pavel Vodicka, Brian M. Wolpin, Ugo Boggi, Patricia Hartge, Gloria M. Petersen, Peter Kraft, Christopher Hautman, Gary E. Goodman, Manal Hassan, Donghui Li, Howard D. Sesso, Malin Sund, Julie E. Buring, Loic Le Marchand, Wei Zheng, Xiao-Ou Shu, Ewa Małecka-Panas, Pavel Soucek, Salvatore Panico, Nicolas Wentzensen, Graham G. Giles, Alpa V. Patel, Daniele Campa, Myron D. Gross, Ghislaine Scelo, J. Michael Gaziano, Juozas Kupcinskas, Debra T. Silverman, Laufey T. Amundadottir, Rachael S. Stolzenberg-Solomon, Neil E. Caporaso, Mazda Jenab, Sara H. Olson, Stefano Landi, Giulia Martina Cavestro, Aruna Kamineni, Laura Beane-Freeman, Roger L. Milne, Rachel E. Neale, Aldo Scarpa, Kathy J. Helzlsouer, Miquel Porta, Emily White, Eric J. Duell, Paige M. Bracci, Nan Hu, Federico Canzian, Eric A. Klein, Gabriele Capurso, Anne Zeleniuch-Jacquotte, Eithne Costello, David J. Hunter, Rudolf Kaaks, Sonja I. Berndt, Kay-Tee Khaw, Nathaniel Rothman, Christian C. Abnet, Francesca Tavano, Christopher A. Haiman, Zhaoming Wang, Ofure Obazee, Alan A. Arslan, Edward Giovannucci, Alison P. Klein, Daniela Basso, Charles Kooperberg, Philip R. Taylor, Satu Männistö, Timothy J. Key, Mark D. Thornquist, Gabriella Andreotti, Lauren K. Brais, Gisella Figlioli, Vittorio Krogh, University Medical Center Utrecht, Imperial College Trust, Cancer Research UK, Medical Research Council UK (MRC), National Institute for Health Research (NIHR), Cancer Research UK (Reino Unido), Medical Research Council (Reino Unido), National Institute for Health Research (Reino Unido), Zhang, Mingfeng, Wang, Zhaoming, Obazee, Ofure, Jia, Jinping, Childs, Erica J, Hoskins, Jason, Figlioli, Gisella, Mocci, Evelina, Collins, Irene, Chung, Charles C, Hautman, Christopher, Arslan, Alan A, Beane Freeman, Laura, Bracci, Paige M, Buring, Julie, Duell, Eric J, Gallinger, Steven, Giles, Graham G, Goodman, Gary E, Goodman, Phyllis J, Kamineni, Aruna, Kolonel, Laurence N, Kulke, Matthew H, Malats, Núria, Olson, Sara H, Sesso, Howard D, Visvanathan, Kala, White, Emily, Zheng, Wei, Abnet, Christian C, Albanes, Demetriu, Andreotti, Gabriella, Brais, Lauren, Bueno de Mesquita, H. Ba, Basso, Daniela, Berndt, Sonja I, Boutron Ruault, Marie Christine, Bijlsma, Maarten F, Brenner, Hermann, Burdette, Laurie, Campa, Daniele, Caporaso, Neil E, Capurso, Gabriele, Cavestro, Giulia Martina, Cotterchio, Michelle, Costello, Eithne, Elena, Joanne, Boggi, Ugo, Gaziano, J. Michael, Gazouli, Maria, Giovannucci, Edward L, Goggins, Michael, Gross, Myron, Haiman, Christopher A, Hassan, Manal, Helzlsouer, Kathy J, Hu, Nan, Hunter, David J, Iskierka Jazdzewska, Elzbieta, Jenab, Mazda, Kaaks, Rudolf, Key, Timothy J, Khaw, Kay Tee, Klein, Eric A, Kogevinas, Manoli, Krogh, Vittorio, Kupcinskas, Juoza, Kurtz, Robert C, Landi, Maria T, Landi, Stefano, Le Marchand, Loic, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L, Neale, Rachel E, Oberg, Ann L, Panico, Salvatore, Patel, Alpa V, Peeters, Petra H. M, Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Purdue, Mark, Quiros, J. Ramón, Riboli, Elio, Rothman, Nathaniel, Scarpa, Aldo, Scelo, Ghislaine, Shu, Xiao Ou, Silverman, Debra T, Soucek, Pavel, Strobel, Oliver, Sund, Malin, Małecka Panas, Ewa, Taylor, Philip R, Tavano, Francesca, Travis, Ruth C, Thornquist, Mark, Tjønneland, Anne, Tobias, Geoffrey S, Trichopoulos, Dimitrio, Vashist, Yogesh, Vodicka, Pavel, Wactawski Wende, Jean, Wentzensen, Nicola, Yu, Herbert, Yu, Kai, Zeleniuch Jacquotte, Anne, Kooperberg, Charle, Risch, Harvey A, Jacobs, Eric J, Li, Donghui, Fuchs, Charle, Hoover, Robert, Hartge, Patricia, Chanock, Stephen J, Petersen, Gloria M, Stolzenberg Solomon, Rachael S, Wolpin, Brian M, Kraft, Peter, Klein, Alison P, Canzian, Federico, Amundadottir, Laufey T., Khaw, Kay-Tee [0000-0002-8802-2903], Apollo - University of Cambridge Repository, CCA -Cancer Center Amsterdam, Center of Experimental and Molecular Medicine, Radiotherapy, Zhang, M, Wang, Z, Obazee, O, Jia, J, Childs, Ej, Hoskins, J, Figlioli, G, Mocci, E, Collins, I, Chung, Cc, Hautman, C, Arslan, Aa, Beane Freeman, L, Bracci, Pm, Buring, J, Duell, Ej, Gallinger, S, Giles, Gg, Goodman, Ge, Goodman, Pj, Kamineni, A, Kolonel, Ln, Kulke, Mh, Malats, N, Olson, Sh, Sesso, Hd, Visvanathan, K, White, E, Zheng, W, Abnet, Cc, Albanes, D, Andreotti, G, Brais, L, Bueno de Mesquita, Hb, Basso, D, Berndt, Si, Boutron Ruault, Mc, Bijlsma, Mf, Brenner, H, Burdette, L, Campa, D, Caporaso, Ne, Capurso, G, Cavestro, GIULIA MARTINA, Cotterchio, M, Costello, E, Elena, J, Boggi, U, Gaziano, Jm, Gazouli, M, Giovannucci, El, Goggins, M, Gross, M, Haiman, Ca, Hassan, M, Helzlsouer, Kj, Hu, N, Hunter, Dj, Iskierka Jazdzewska, E, Jenab, M, Kaaks, R, Key, Tj, Khaw, Kt, Klein, Ea, Kogevinas, M, Krogh, V, Kupcinskas, J, Kurtz, Rc, Landi, Mt, Landi, S, Le Marchand, L, Mambrini, A, Mannisto, S, Milne, Rl, Neale, Re, Oberg, Al, Panico, S, Patel, Av, Peeters, Ph, Peters, U, Pezzilli, R, Porta, M, Purdue, M, Quiros, Jr, Riboli, E, Rothman, N, Scarpa, A, Scelo, G, Shu, Xo, Silverman, Dt, Soucek, P, Strobel, O, Sund, M, Małecka Panas, E, Taylor, Pr, Tavano, F, Travis, Rc, Thornquist, M, Tjønneland, A, Tobias, G, Trichopoulos, D, Vashist, Y, Vodicka, P, Wactawski Wende, J, Wentzensen, N, Yu, H, Yu, K, Zeleniuch Jacquotte, A, Kooperberg, C, Risch, Ha, Jacobs, Ej, Li, D, Fuchs, C, Hoover, R, Hartge, P, Chanock, Sj, Petersen, Gm, Stolzenberg Solomon, R, Wolpin, Bm, Kraft, P, Klein, Ap, Canzian, F, and Amundadottir, L. T.
Subjects: 0301 basic medicine, Candidate gene, Pancreatic disease, GENETIC SUSCEPTIBILITY, pancreatic cancer, Datasets as Topic, Genome-wide association study, imputation, TRET, 0302 clinical medicine, Fine-mapping, GWAS, Imputation, NR5A2, Pancreatic cancer, Oncology, Genotype, Genetics, 3. Good health, fine-mapping, Chromosomes, Human, Pair 1, 030220 oncology & carcinogenesis, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 8, 616.37-006.6 [udc], BLADDER-CANCER, Single-nucleotide polymorphism, GENOTYPE IMPUTATION, BREAST, Polymorphism, Single Nucleotide, 03 medical and health sciences, Journal Article, medicine, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Pàncrees -- Càncer, Cancer och onkologi, LONG-RANGE INTERACTION, business.industry, medicine.disease, Pancreatic neoplasms, genetics, Polymorphism, single nucleotide, RISK LOCI, Fold change, COMMON VARIANT, Cromosomes, Pancreatic Neoplasms, 030104 developmental biology, Cancer and Oncology, business, Imputation (genetics), LRH-1, Priority Research Paper, Genome-Wide Association Study
Abstract: Altres ajuts: The authors acknowledge the contribution of the staff of the Cancer Genomics Research Laboratory (CGR) at the National Cancer Institute, NIH, for their help throughout the project. This work was supported by the Intramural Research Program of the US National Institutes of Health (NIH), National Cancer Institute. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. Additional acknowledgements for individual participating studies are listed in the Supplemental Materials. Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88×10 −15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22×10 −9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70×10 −8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 (NR5A2), chr8q24.21 (MYC) and chr5p15.33 (CLPTM1L - TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal (n = 10) and tumor (n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7×10 −8). This finding was validated in a second set of paired (n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5×10 −4 -2.0×10 −3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
Published: 2016

39. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer

Author: Christopher A. Haiman, Herbert Yu, Lauren K. Brais, Gabriele Capurso, Eric J. Duell, Michelle Cotterchio, Núria Malats, Beatrice Mohelníková-Duchoňová, Claudio Pasquali, Gary E. Goodman, Giulia Martina Cavestro, Kala Visvanathan, Sean P. Cleary, Jill P. Smith, Jean Wactawski-Wende, Rita T. Lawlor, Gianluca Severi, J. Michael Gaziano, Kathy J. Helzlsouer, Charles C. Chung, Harvey A. Risch, Stephen K. Van Den Eeden, Elizabeth A. Holly, Bas Bueno-de-Mesquita, Patricia Hartge, Fei Chen, Mark D. Thornquist, Hermann Brenner, Ulrike Peters, Ghislaine Scelo, Steven Gallinger, Sonja I. Berndt, Howard D. Sesso, Lenka Foretova, Laufey T. Amundadottir, Mingfeng Zhang, Federico Canzian, Rudolf Kaaks, Stephen J. Chanock, Nicolas Wentzensen, Ann L. Oberg, Eric J. Jacobs, Peter Kraft, Rayjean J. Hung, Evelina Mocci, Maria Gazouli, Francesca Tavano, Michael Borges, Zhaoming Wang, Alan A. Arslan, Wei Zheng, Ayelet Borgida, Paige M. Bracci, Jason W. Hoskins, William R. Bamlet, Juozas Kupcinskas, Joseph M. Herman, Demetrius Albanes, Charles S. Fuchs, Nathaniel Rothman, Niccola Funel, Pavel Soucek, Edward Giovannucci, Paul Brennan, Thilo Hackert, Jun Zhong, Manolis Kogevinas, Robert N. Hoover, Michael Goggins, Amanda L. Blackford, Robert J. Kurtz, Malin Sund, Roger L. Milne, Stefano Landi, Francisco X. Real, Emily White, Miquel Porta, Ivana Holcatova, Kari G. Chaffee, Vladimir Janout, Charles Kooperberg, Péter Hegyi, Frederike Dijk, Yogesh K. Vashist, Andrea Mambrini, Matthew H. Kulke, I. Min Lee, Kai Yu, Alison P. Klein, Phyllis J. Goodman, Donghui Li, Julie E. Buring, Debra T. Silverman, Ana Babic, John P. Neoptolemos, Erica J. Childs, Alpa V. Patel, Sara H. Olson, Brian M. Wolpin, Krzysztof Jamroziak, Gloria M. Petersen, Xiao-Ou Shu, Renata Talar-Wojnarowska, Rachel E. Neale, Daniel A. Laheru, Kay-Tee Khaw, Eric A. Klein, Ashley Jermusyk, Graham G. Giles, Daniele Campa, Laura Beane-Freeman, Rachael Z. Stolzenberg-Solomon, Raffaele Pezzilli, Geoffrey S. Tobias, Pavel Vodicka, Irene Orlow, Anne Zeleniuch-Jacquotte, Ofure Obazee, Satu Männistö, Lingeng Lu, Manal Hasan, Loic LeMarchand, Gabriella Andreotti, CCA - Cancer biology and immunology, Pathology, Lung Cancer Research Foundation, Sol Goldman Pancreas Cancer Research Center, Geoffrey Beene Foundation, Arnold and Arlene Goldstein Family Foundation, National Health and Medical Research Council (Australia), Czech Science Foundation, Joan Rombauer Pancreatic Cancer Foundation, NIH - National Cancer Institute (NCI) (Estados Unidos), Instituto de Salud Carlos III, Ministerio de Ciencia y Tecnología (España), Red Temática de Investigación Cooperativa en Cáncer (España), Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública), Mocci, Evelina [0000-0002-7101-9556], Canzian, Federico [0000-0002-4261-4583], Chaffee, Kari G [0000-0002-7313-1875], Dijk, Frederike [0000-0003-3970-6601], Gazouli, Maria [0000-0002-3295-6811], Jacobs, Eric J [0000-0002-8458-7659], Klein, Eric A [0000-0002-1783-0698], Lu, Lingeng [0000-0001-9871-0809], Malats, Núria [0000-0003-2538-3784], Milne, Roger L [0000-0001-5764-7268], Neoptolemos, John P [0000-0002-6201-7399], Oberg, Ann L [0000-0003-2539-9807], Pezzilli, Raffaele [0000-0001-9827-7451], Porta, Miquel [0000-0003-1684-7428], Real, Francisco X [0000-0001-9501-498X], Sund, Malin [0000-0002-7516-9543], Tobias, Geoffrey S [0000-0002-2878-8253], Van Den Eeden, Stephen K [0000-0002-5599-8387], Yu, Herbert [0000-0003-3950-4815], Zheng, Wei [0000-0003-1226-070X], Obazee, Ofure [0000-0001-8791-5008], Amundadottir, Laufey T [0000-0003-1859-8971], Apollo - University of Cambridge Repository, Klein, Alison P., Wolpin, Brian M., Risch, Harvey A., Stolzenberg-Solomon, Rachael Z., Mocci, Evelina, Zhang, Mingfeng, Canzian, Federico, Childs, Erica J., Hoskins, Jason W., Jermusyk, Ashley, Zhong, Jun, Chen, Fei, Albanes, Demetriu, Andreotti, Gabriella, Arslan, Alan A., Babic, Ana, Bamlet, William R., Beane-Freeman, Laura, Berndt, Sonja I., Blackford, Amanda, Borges, Michael, Borgida, Ayelet, Bracci, Paige M., Brais, Lauren, Brennan, Paul, Brenner, Hermann, Bueno-De-Mesquita, Ba, Buring, Julie, Campa, Daniele, Capurso, Gabriele, Cavestro, Giulia Martina, Chaffee, Kari G., Chung, Charles C., Cleary, Sean, Cotterchio, Michelle, Dijk, Frederike, Duell, Eric J., Foretova, Lenka, Fuchs, Charle, Funel, Niccola, Gallinger, Steven, Gaziano, J. Michael M., Gazouli, Maria, Giles, Graham G., Giovannucci, Edward, Goggins, Michael, Goodman, Gary E., Goodman, Phyllis J., Hackert, Thilo, Haiman, Christopher, Hartge, Patricia, Hasan, Manal, Hegyi, Peter, Helzlsouer, Kathy J., Herman, Joseph, Holcatova, Ivana, Holly, Elizabeth A., Hoover, Robert, Hung, Rayjean J., Jacobs, Eric J., Jamroziak, Krzysztof, Janout, Vladimir, Kaaks, Rudolf, Khaw, Kay-Tee, Klein, Eric A., Kogevinas, Manoli, Kooperberg, Charle, Kulke, Matthew H., Kupcinskas, Juoza, Kurtz, Robert J., Laheru, Daniel, Landi, Stefano, Lawlor, Rita T., Lee, I. -Min, Lemarchand, Loic, Lu, Lingeng, Malats, Núria, Mambrini, Andrea, Mannisto, Satu, Milne, Roger L., Mohelníková-Duchoňová, Beatrice, Neale, Rachel E., Neoptolemos, John P., Oberg, Ann L., Olson, Sara H., Orlow, Irene, Pasquali, Claudio, Patel, Alpa V., Peters, Ulrike, Pezzilli, Raffaele, Porta, Miquel, Real, Francisco X., Rothman, Nathaniel, Scelo, Ghislaine, Sesso, Howard D., Severi, Gianluca, Shu, Xiao-Ou, Silverman, Debra, Smith, Jill P., Soucek, Pavel, Sund, Malin, Talar-Wojnarowska, Renata, Tavano, Francesca, Thornquist, Mark D., Tobias, Geoffrey S., Van Den Eeden, Stephen K., Vashist, Yogesh, Visvanathan, Kala, Vodicka, Pavel, Wactawski-Wende, Jean, Wang, Zhaoming, Wentzensen, Nicola, White, Emily, Yu, Herbert, Yu, Kai, Zeleniuch-Jacquotte, Anne, Zheng, Wei, Kraft, Peter, Li, Donghui, Chanock, Stephen, Obazee, Ofure, Petersen, Gloria M., and Amundadottir, Laufey T.
Subjects: 0301 basic medicine, Oncology, Genetics and Molecular Biology (all), Pancreatic disease, Chemistry(all), General Physics and Astronomy, Genome-wide association study, Disease, Biochemistry, DISEASE, Tensins, Databases, Genetic, IMPUTATION, 03.02. Klinikai orvostan, lcsh:Science, Càncer, Pancreas cancer, GENE-EXPRESSION, Cancer, RISK, Multidisciplinary, Chemistry (all), Pancreatic Neoplasm, Intracellular Signaling Peptides and Proteins, HNF1B, 3. Good health, TRANSCRIPTION FACTORS, Hepatocyte Nuclear Factor 4, Intercellular Signaling Peptides and Proteins, Human, Carcinoma, Pancreatic Ductal, medicine.medical_specialty, Science, Physics and Astronomy(all), Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Physics and Astronomy (all), Cancer epidemiology, Pancreatic cancer, Internal medicine, medicine, Carcinoma, Humans, Genetic Predisposition to Disease, Allele, Càncer de pàncrees, Hepatocyte Nuclear Factor 1-beta, Cancer och onkologi, Biochemistry, Genetics and Molecular Biology (all), business.industry, Biochemistry, Genetics and Molecular Biology(all), Protein, Proteins, ADENOCARCINOMA, General Chemistry, Repressor Protein, medicine.disease, Pancreatic Neoplasms, Repressor Proteins, BODY-MASS INDEX, 030104 developmental biology, Tensin, Cancer and Oncology, Expression quantitative trait loci, lcsh:Q, business, ASSOCIATION ANALYSES, Genetics and Molecular Biology(all), Genome-Wide Association Study
Abstract: In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 × 10−8). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PANDoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 × 10−14), rs2941471 at 8q21.11 (HNF4G, P = 6.60 × 10−10), rs4795218 at 17q12 (HNF1B, P = 1.32 × 10−8), and rs1517037 at 18q21.32 (GRP, P = 3.28 × 10−8). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene., Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.

40. A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer.

Author: Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, Zhang M, Song L, Chung CC, Zhang T, Xiao W, Albanes D, Andreotti G, Arslan AA, Babic A, Bamlet WR, Beane-Freeman L, Berndt S, Borgida A, Bracci PM, Brais L, Brennan P, Bueno-de-Mesquita B, Buring J, Canzian F, Childs EJ, Cotterchio M, Du M, Duell EJ, Fuchs C, Gallinger S, Gaziano JM, Giles GG, Giovannucci E, Goggins M, Goodman GE, Goodman PJ, Haiman C, Hartge P, Hasan M, Helzlsouer KJ, Holly EA, Klein EA, Kogevinas M, Kurtz RJ, LeMarchand L, Malats N, Männistö S, Milne R, Neale RE, Ng K, Obazee O, Oberg AL, Orlow I, Patel AV, Peters U, Porta M, Rothman N, Scelo G, Sesso HD, Severi G, Sieri S, Silverman D, Sund M, Tjønneland A, Thornquist MD, Tobias GS, Trichopoulou A, Van Den Eeden SK, Visvanathan K, Wactawski-Wende J, Wentzensen N, White E, Yu H, Yuan C, Zeleniuch-Jacquotte A, Hoover R, Brown K, Kooperberg C, Risch HA, Jacobs EJ, Li D, Yu K, Shu XO, Chanock SJ, Wolpin BM, Stolzenberg-Solomon RZ, Chatterjee N, Klein AP, Smith JP, Kraft P, Shi J, Petersen GM, Zheng W, and Amundadottir LT
Subjects: Databases, Genetic, Gene Expression, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Transcriptome, Pancreatic Neoplasms genetics
Abstract: Background: Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown., Methods: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples)., Results: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction., Conclusions: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation., (Published by Oxford University Press 2020. This work is written by US Government employees and is in the public domain in the US.)
Published: 2020
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