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2. Pleiotropic Associations of Risk Variants Identified for Other Cancers With Lung Cancer Risk: The PAGE and TRICL Consortia

Author

Park, Lani S., Fesinmeyer, Megan D., Timofeeva, Maria, Caberto, Christian P., Kocarnik, Jonathan M., Han, Younghun, Love, Shelly-Ann, Young, Alicia, Dumitrescu, Logan, Lin, Yi, Goodloe, Robert, Wilkens, Lynne R., Hindorff, Lucia, Fowke, Jay H., Carty, Cara, Buyske, Steven, Schumacher, Frederick R., Butler, Anne, Dilks, Holli, Deelman, Ewa, Cote, Michele L., Chen, Wei, Pande, Mala, Christiani, David C., Field, John K., Bickeböller, Heike, Risch, Angela, Heinrich, Joachim, Brennan, Paul, Wang, Yufei, Eisen, Timothy, Houlston, Richard S., Thun, Michael, Albanes, Demetrius, Caporaso, Neil, Peters, Ulrike, North, Kari E., Heiss, Gerardo, Crawford, Dana C., Bush, William S., Haiman, Christopher A., Landi, Maria Teresa, Hung, Rayjean J., Kooperberg, Charles, Amos, Christopher I., Le Marchand, Loïc, and Cheng, Iona

Published
2014
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3. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation.

Author

Gusev, Alexander, Shi, Huwenbo, Kichaev, Gleb, Pomerantz, Mark, Li, Fugen, Long, Henry W, Ingles, Sue A, Kittles, Rick A, Strom, Sara S, Rybicki, Benjamin A, Nemesure, Barbara, Isaacs, William B, Zheng, Wei, Pettaway, Curtis A, Yeboah, Edward D, Tettey, Yao, Biritwum, Richard B, Adjei, Andrew A, Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chokkalingam, Anand P, John, Esther M, Murphy, Adam B, Signorello, Lisa B, Carpten, John, Leske, M Cristina, Wu, Suh-Yuh, Hennis, Anslem J M, Neslund-Dudas, Christine, Hsing, Ann W, Chu, Lisa, Goodman, Phyllis J, Klein, Eric A, Witte, John S, Casey, Graham, Kaggwa, Sam, Cook, Michael B, Stram, Daniel O, Blot, William J, Eeles, Rosalind A, Easton, Douglas, Kote-Jarai, ZSofia, Al Olama, Ali Amin, Benlloch, Sara, Muir, Kenneth, Giles, Graham G, Southey, Melissa C, Fitzgerald, Liesel M, Gronberg, Henrik, Wiklund, Fredrik, Aly, Markus, Henderson, Brian E, Schleutker, Johanna, Wahlfors, Tiina, Tammela, Teuvo L J, Nordestgaard, Børge G, Key, Tim J, Travis, Ruth C, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Pharoah, Paul, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S, Cybulski, Cezary, Wokolorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa, Teerlink, Craig, Brenner, Hermann, Dieffenbach, Aida K, Arndt, Volker, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Batra, Jyotsna, Spurdle, Amanda, Clements, Judith A, Teixeira, Manuel R, Pandha, Hardev, Michael, Agnieszka, Paulo, Paula, Maia, Sofia, Kierzek, Andrzej, Conti, David V, Albanes, Demetrius, Berg, Christine, Berndt, Sonja I, Campa, Daniele, Crawford, E David, Diver, W Ryan, Gapstur, Susan M, Gaziano, J Michael, Giovannucci, Edward, Hoover, Robert, Hunter, David J, Johansson, Mattias, Kraft, Peter, Le Marchand, Loic, Lindström, Sara, Navarro, Carmen, Overvad, Kim, Riboli, Elio, Siddiq, Afshan, Stevens, Victoria L, Trichopoulos, Dimitrios, Vineis, Paolo, Yeager, Meredith, Trynka, Gosia, Raychaudhuri, Soumya, Schumacher, Frederick R, Price, Alkes L, Freedman, Matthew L, Haiman, Christopher A, Pasaniuc, Bogdan, Gusev, Alexander, Shi, Huwenbo, Kichaev, Gleb, Pomerantz, Mark, Li, Fugen, Long, Henry W, Ingles, Sue A, Kittles, Rick A, Strom, Sara S, Rybicki, Benjamin A, Nemesure, Barbara, Isaacs, William B, Zheng, Wei, Pettaway, Curtis A, Yeboah, Edward D, Tettey, Yao, Biritwum, Richard B, Adjei, Andrew A, Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chokkalingam, Anand P, John, Esther M, Murphy, Adam B, Signorello, Lisa B, Carpten, John, Leske, M Cristina, Wu, Suh-Yuh, Hennis, Anslem J M, Neslund-Dudas, Christine, Hsing, Ann W, Chu, Lisa, Goodman, Phyllis J, Klein, Eric A, Witte, John S, Casey, Graham, Kaggwa, Sam, Cook, Michael B, Stram, Daniel O, Blot, William J, Eeles, Rosalind A, Easton, Douglas, Kote-Jarai, ZSofia, Al Olama, Ali Amin, Benlloch, Sara, Muir, Kenneth, Giles, Graham G, Southey, Melissa C, Fitzgerald, Liesel M, Gronberg, Henrik, Wiklund, Fredrik, Aly, Markus, Henderson, Brian E, Schleutker, Johanna, Wahlfors, Tiina, Tammela, Teuvo L J, Nordestgaard, Børge G, Key, Tim J, Travis, Ruth C, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Pharoah, Paul, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S, Cybulski, Cezary, Wokolorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa, Teerlink, Craig, Brenner, Hermann, Dieffenbach, Aida K, Arndt, Volker, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Batra, Jyotsna, Spurdle, Amanda, Clements, Judith A, Teixeira, Manuel R, Pandha, Hardev, Michael, Agnieszka, Paulo, Paula, Maia, Sofia, Kierzek, Andrzej, Conti, David V, Albanes, Demetrius, Berg, Christine, Berndt, Sonja I, Campa, Daniele, Crawford, E David, Diver, W Ryan, Gapstur, Susan M, Gaziano, J Michael, Giovannucci, Edward, Hoover, Robert, Hunter, David J, Johansson, Mattias, Kraft, Peter, Le Marchand, Loic, Lindström, Sara, Navarro, Carmen, Overvad, Kim, Riboli, Elio, Siddiq, Afshan, Stevens, Victoria L, Trichopoulos, Dimitrios, Vineis, Paolo, Yeager, Meredith, Trynka, Gosia, Raychaudhuri, Soumya, Schumacher, Frederick R, Price, Alkes L, Freedman, Matthew L, Haiman, Christopher A, and Pasaniuc, Bogdan

Abstract

Although genome-wide association studies have identified over 100 risk loci that explain ∼33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

Published
2016
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4. Atlas of prostate cancer heritability in European and African-American men pinpoints tissue-specific regulation

Author

University of Helsinki, Clinicum, Gusev, Alexander, Shi, Huwenbo, Kichaev, Gleb, Pomerantz, Mark, Li, Fugen, Long, Henry W., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Zheng, Wei, Pettaway, Curtis A., Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chokkalingam, Anand P., John, Esther M., Murphy, Adam B., Signorello, Lisa B., Carpten, John, Leske, M. Cristina, Wu, Suh-Yuh, Hennis, Anslem J. M., Neslund-Dudas, Christine, Hsing, Ann W., Chu, Lisa, Goodman, Phyllis J., Klein, Eric A., Witte, John S., Casey, Graham, Kaggwa, Sam, Cook, Michael B., Stram, Daniel O., Blot, William J., Eeles, Rosalind A., Easton, Douglas, Kote-Jarai, ZSofia, Al Olama, Ali Amin, Benlloch, Sara, Muir, Kenneth, Giles, Graham G., Southey, Melissa C., Fitzgerald, Liesel M., Gronberg, Henrik, Wiklund, Fredrik, Aly, Markus, Henderson, Brian E., Schleutker, Johanna, Wahlfors, Tiina, Tammela, Teuvo L. J., Nordestgaard, Borge G., Key, Tim J., Travis, Ruth C., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Pharoah, Paul, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L., Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S., Cybulski, Cezary, Wokolorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa, Teerlink, Craig, Brenner, Hermann, Dieffenbach, Aida K., Arndt, Volker, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Batra, Jyotsna, Spurdle, Amanda, Clements, Judith A., Teixeira, Manuel R., Pandha, Hardev, Michael, Agnieszka, Paulo, Paula, Maia, Sofia, Kierzek, Andrzej, Conti, David V., Albanes, Demetrius, Berg, Christine, Berndt, Sonja I., Campa, Daniele, Crawford, E. David, Diver, W. Ryan, Gapstur, Susan M., Gaziano, J. Michael, Giovannucci, Edward, Hoover, Robert, Hunter, David J., Johansson, Mattias, Kraft, Peter, Le Marchand, Loic, Lindstrom, Sara, Navarro, Carmen, Overvad, Kim, Riboli, Elio, Siddiq, Afshan, Stevens, Victoria L., Trichopoulos, Dimitrios, Vineis, Paolo, Yeager, Meredith, Trynka, Gosia, Raychaudhuri, Soumya, Schumacher, Frederick R., Price, Alkes L., Freedman, Matthew L., Haiman, Christopher A., Pasaniuc, Bogdan, Cook, Margaret, Guy, Michelle, Govindasami, Koveela, Leongamornlert, Daniel, Sawyer, Emma J., Wilkinson, Rosemary, Saunders, Edward J., Tymrakiewicz, Malgorzata, Dadaev, Tokhir, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Lophatananon, Artitaya, Pedersen, John, Hopper, John L., Adolfson, Jan, Stattin, Paer, Johansson, Jan-Erik, Cavalli-Bjoerkman, Carin, Karlsson, Ami, Broms, Michael, Auvinen, Anssi, Kujala, Paula, Maattanen, Liisa, Murtola, Teemu, Taari, Kimmo, Weischer, Maren, Nielsen, Sune F., Klarskov, Peter, Roder, Andreas, Iversen, Peter, Wallinder, Hans, Gustafsson, Sven, Cox, Angela, Brown, Paul, George, Anne, Marsden, Gemma, Lane, Athene, Davis, Michael, Tillmans, Lori, Riska, Shaun, Wang, Liang, Rinckleb, Antje, Lubiski, Jan, Stegmaier, Christa, Pow-Sang, Julio, Park, Hyun, Radlein, Selina, Rincon, Maria, Haley, James, Zachariah, Babu, Kachakova, Darina, Popov, Elenko, Mitkova, Atanaska, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Heathcote, Peter, Wood, Glenn, Malone, Greg, Saunders, Pamela, Eckert, Allison, Yeadon, Trina, Kerr, Kris, Collins, Angus, Turner, Megan, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Alexander, Kimberly, Omara, Tracy, Wu, Huihai, Henrique, Rui, Pinto, Pedro, Santos, Joana, Barros-Silva, Joao, PRACTICAL Consortium, University of Helsinki, Clinicum, Gusev, Alexander, Shi, Huwenbo, Kichaev, Gleb, Pomerantz, Mark, Li, Fugen, Long, Henry W., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Zheng, Wei, Pettaway, Curtis A., Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chokkalingam, Anand P., John, Esther M., Murphy, Adam B., Signorello, Lisa B., Carpten, John, Leske, M. Cristina, Wu, Suh-Yuh, Hennis, Anslem J. M., Neslund-Dudas, Christine, Hsing, Ann W., Chu, Lisa, Goodman, Phyllis J., Klein, Eric A., Witte, John S., Casey, Graham, Kaggwa, Sam, Cook, Michael B., Stram, Daniel O., Blot, William J., Eeles, Rosalind A., Easton, Douglas, Kote-Jarai, ZSofia, Al Olama, Ali Amin, Benlloch, Sara, Muir, Kenneth, Giles, Graham G., Southey, Melissa C., Fitzgerald, Liesel M., Gronberg, Henrik, Wiklund, Fredrik, Aly, Markus, Henderson, Brian E., Schleutker, Johanna, Wahlfors, Tiina, Tammela, Teuvo L. J., Nordestgaard, Borge G., Key, Tim J., Travis, Ruth C., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Pharoah, Paul, Pashayan, Nora, Khaw, Kay-Tee, Stanford, Janet L., Thibodeau, Stephen N., McDonnell, Shannon K., Schaid, Daniel J., Maier, Christiane, Vogel, Walther, Luedeke, Manuel, Herkommer, Kathleen, Kibel, Adam S., Cybulski, Cezary, Wokolorczyk, Dominika, Kluzniak, Wojciech, Cannon-Albright, Lisa, Teerlink, Craig, Brenner, Hermann, Dieffenbach, Aida K., Arndt, Volker, Park, Jong Y., Sellers, Thomas A., Lin, Hui-Yi, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Batra, Jyotsna, Spurdle, Amanda, Clements, Judith A., Teixeira, Manuel R., Pandha, Hardev, Michael, Agnieszka, Paulo, Paula, Maia, Sofia, Kierzek, Andrzej, Conti, David V., Albanes, Demetrius, Berg, Christine, Berndt, Sonja I., Campa, Daniele, Crawford, E. David, Diver, W. Ryan, Gapstur, Susan M., Gaziano, J. Michael, Giovannucci, Edward, Hoover, Robert, Hunter, David J., Johansson, Mattias, Kraft, Peter, Le Marchand, Loic, Lindstrom, Sara, Navarro, Carmen, Overvad, Kim, Riboli, Elio, Siddiq, Afshan, Stevens, Victoria L., Trichopoulos, Dimitrios, Vineis, Paolo, Yeager, Meredith, Trynka, Gosia, Raychaudhuri, Soumya, Schumacher, Frederick R., Price, Alkes L., Freedman, Matthew L., Haiman, Christopher A., Pasaniuc, Bogdan, Cook, Margaret, Guy, Michelle, Govindasami, Koveela, Leongamornlert, Daniel, Sawyer, Emma J., Wilkinson, Rosemary, Saunders, Edward J., Tymrakiewicz, Malgorzata, Dadaev, Tokhir, Morgan, Angela, Fisher, Cyril, Hazel, Steve, Livni, Naomi, Lophatananon, Artitaya, Pedersen, John, Hopper, John L., Adolfson, Jan, Stattin, Paer, Johansson, Jan-Erik, Cavalli-Bjoerkman, Carin, Karlsson, Ami, Broms, Michael, Auvinen, Anssi, Kujala, Paula, Maattanen, Liisa, Murtola, Teemu, Taari, Kimmo, Weischer, Maren, Nielsen, Sune F., Klarskov, Peter, Roder, Andreas, Iversen, Peter, Wallinder, Hans, Gustafsson, Sven, Cox, Angela, Brown, Paul, George, Anne, Marsden, Gemma, Lane, Athene, Davis, Michael, Tillmans, Lori, Riska, Shaun, Wang, Liang, Rinckleb, Antje, Lubiski, Jan, Stegmaier, Christa, Pow-Sang, Julio, Park, Hyun, Radlein, Selina, Rincon, Maria, Haley, James, Zachariah, Babu, Kachakova, Darina, Popov, Elenko, Mitkova, Atanaska, Vlahova, Aleksandrina, Dikov, Tihomir, Christova, Svetlana, Heathcote, Peter, Wood, Glenn, Malone, Greg, Saunders, Pamela, Eckert, Allison, Yeadon, Trina, Kerr, Kris, Collins, Angus, Turner, Megan, Srinivasan, Srilakshmi, Kedda, Mary-Anne, Alexander, Kimberly, Omara, Tracy, Wu, Huihai, Henrique, Rui, Pinto, Pedro, Santos, Joana, Barros-Silva, Joao, and PRACTICAL Consortium

Abstract

Although genome-wide association studies have identified over 100 risk loci that explain similar to 33% of familial risk for prostate cancer (PrCa), their functional effects on risk remain largely unknown. Here we use genotype data from 59,089 men of European and African American ancestries combined with cell-type-specific epigenetic data to build a genomic atlas of single-nucleotide polymorphism (SNP) heritability in PrCa. We find significant differences in heritability between variants in prostate-relevant epigenetic marks defined in normal versus tumour tissue as well as between tissue and cell lines. The majority of SNP heritability lies in regions marked by H3k27 acetylation in prostate adenoc7arcinoma cell line (LNCaP) or by DNaseI hypersensitive sites in cancer cell lines. We find a high degree of similarity between European and African American ancestries suggesting a similar genetic architecture from common variation underlying PrCa risk. Our findings showcase the power of integrating functional annotation with genetic data to understand the genetic basis of PrCa.

Published
2016

5. seXY: a tool for sex inference from genotype arrays

Author

Qian, David C, primary, Busam, Jonathan A, additional, Xiao, Xiangjun, additional, O’Mara, Tracy A, additional, Eeles, Rosalind A, additional, Schumacher, Frederick R, additional, Phelan, Catherine M, additional, and Amos, Christopher I, additional

Published
2016
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6. Pleiotropic Associations of Risk Variants Identified for Other Cancers With Lung Cancer Risk: The PAGE and TRICL Consortia

Author

Schumacher, Frederick R., Deelman, Ewa, Fesinmeyer, Megan D., Love, Shelly-Ann, Eisen, Timothy, Christiani, David C., Risch, Angela, Dilks, Holli, Chen, Wei, Buyske, Steven, Houlston, Richard S., Fowke, Jay H., Wang, Yufei, Brennan, Paul, Young, Alicia, Hindorff, Lucia, Butler, Anne, Heinrich, Joachim, Field, John K., Cote, Michele L., Bickebӧller, Heike, Carty, Cara, Lin, Yi, Wilkens, Lynne R., Kocarnik, Jonathan M., Dumitrescu, Logan, Park, S. Lani, Pande, Mala, Han, Younghun, Caberto, Christian P., Goodloe, Robert, and Timofeeva, Maria

Abstract

BackgroundGenome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed.MethodsWe included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non–lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10–5 was used to assign statistical significance.ResultsThe breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10–6). This association was strongest for women with adenocarcinoma (P = 1.2×10–4) and not statistically significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10–8) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10–5), respectively.ConclusionsOur findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.

Published
2014
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7. Genetic Variation in the Vitamin D Pathway in Relation to Risk of Prostate Cancer:Results from Breast and Prostate Cancer Cohort Consortium (BPC3)

Author

Mondul, Alison M, Shui, Irene M, Yu, Kai, Travis, Ruth C, Stevens, Victoria L, Campa, Daniele, Schumacher, Frederick R, Ziegler, Regina G, Bueno-de-Mesquita, H Bas, Berndt, Sonja, Crawford, E David, Gapstur, Susan M, Gaziano, John Michael, Giovannucci, Edward, Haiman, Christopher A, Henderson, Brian E, Hunter, David J, Johansson, Mattias, Key, Timothy J, Le Marchand, Loic, Lindstrom, Sara, McCullough, Marjorie L, Navarro, Carmen, Overvad, Kim, Palli, Domenico, Purdue, Mark, Stampfer, Meir J, Weinstein, Stephanie J, Willett, Walter C, Yeager, Meredith, Chanock, Stephen J, Trichopoulos, Dimitrios, Kolonel, Laurence N, Kraft, Peter, and Albanes, Demetrius

Abstract

BACKGROUND: Studies suggest that vitamin D status may be associated with prostate cancer risk, although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D (25(OH)D) status. We examined SNPs in four genes shown to predict circulating levels of 25(OH)D in relation to prostate cancer risk. METHODS: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the NCI Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. RESULTS: We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D (per A allele, OR=0.86, 95%CI=0.80-0.93, p-trend=0.0002), but an increased risk for non-aggressive disease (per a allele: OR=1.10, 95%CI=1.04-1.17, p-trend=0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles = 0.66, 95% CI = 0.44 - 0.98; p-trend=0.003). CONCLUSIONS: In this large, pooled analysis, genetic variants related to lower 25(OH)D were associated with a decreased risk of aggressive prostate cancer. Impact: Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk.

Published
2013
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8. Genetic Variation in the Vitamin D Pathway in Relation to Risk of Prostate Cancer—Results from the Breast and Prostate Cancer Cohort Consortium

Author

Mondul, Alison M., primary, Shui, Irene M., additional, Yu, Kai, additional, Travis, Ruth C., additional, Stevens, Victoria L., additional, Campa, Daniele, additional, Schumacher, Frederick R., additional, Ziegler, Regina G., additional, Bueno-de-Mesquita, H. Bas, additional, Berndt, Sonja, additional, Crawford, E.D., additional, Gapstur, Susan M., additional, Gaziano, J. Michael, additional, Giovannucci, Edward, additional, Haiman, Christopher A., additional, Henderson, Brian E., additional, Hunter, David J., additional, Johansson, Mattias, additional, Key, Timothy J., additional, Marchand, Loïc Le, additional, Lindström, Sara, additional, McCullough, Marjorie L., additional, Navarro, Carmen, additional, Overvad, Kim, additional, Palli, Domenico, additional, Purdue, Mark, additional, Stampfer, Meir J., additional, Weinstein, Stephanie J., additional, Willett, Walter C., additional, Yeager, Meredith, additional, Chanock, Stephen J., additional, Trichopoulos, Dimitrios, additional, Kolonel, Laurence N., additional, Kraft, Peter, additional, and Albanes, Demetrius, additional

Published
2013
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10. seXY: a tool for sex inference from genotype arrays.

Author

Qian, David C., Busam, Jonathan A., Xiangjun Xiao, O'Mara, Tracy A., Eeles, Rosalind A., Schumacher, Frederick R., Phelan, Catherine M., and Amos, Christopher I.

Subjects
GENOTYPES, GENOMES, HUMAN sexuality, X chromosome, Y chromosome, LOGISTIC regression analysis
Abstract

Motivation: Checking concordance between reported sex and genotype-inferred sex is a crucial quality control measure in genome-wide association studies (GWAS). However, limited insights exist regarding the true accuracy of software that infer sex from genotype array data. Results: We present seXY, a logistic regression model trained on both X chromosome heterozygosity and Y chromosome missingness, that consistently demonstrated>99.5% sex inference accuracy in cross-validation for 889 males and 5,361 females enrolled in prostate cancer and ovarian cancer GWAS. Compared to PLINK, one of the most popular tools for sex inference in GWAS that assesses only X chromosome heterozygosity, seXY achieved marginally better male classification and 3% more accurate female classification. [ABSTRACT FROM AUTHOR]

Published
2017
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