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1. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, and Lu, Yong-Jie

Subjects
Male, Urologic Diseases, Aging, Quantitative Trait Loci, Medical and Health Sciences, Risk Factors, Clinical Research, Odds Ratio, Genetics, Humans, 2.1 Biological and endogenous factors, Neoplasm Invasiveness, Genetic Predisposition to Disease, Aetiology, Cancer, Prevention, Prostate Cancer, Racial Groups, Human Genome, Prostatic Neoplasms, Molecular Sequence Annotation, Genomics, Middle Aged, Biological Sciences, Phenotype, Good Health and Well Being, Genetic Loci, Software, Genome-Wide Association Study, Statistical Distributions, Developmental Biology
Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Published
2021

2. Genome-wide association study of prostate cancer in men of African ancestry identifies a susceptibility locus at 17q21

Author

Haiman, Christopher A, Chen, Gary K, Blot, William J, Strom, Sara S, Berndt, Sonja I, Kittles, Rick A, Rybicki, Benjamin A, Isaacs, William B, Ingles, Sue A, Stanford, Janet L, Diver, W Ryan, Witte, John S, Hsing, Ann W, Nemesure, Barbara, Rebbeck, Timothy R, Cooney, Kathleen A, Xu, Jianfeng, Kibel, Adam S, Hu, Jennifer J, John, Esther M, Gueye, Serigne M, Watya, Stephen, Signorello, Lisa B, Hayes, Richard B, Wang, Zhaoming, Yeboah, Edward, Tettey, Yao, Cai, Qiuyin, Kolb, Suzanne, Ostrander, Elaine A, Zeigler-Johnson, Charnita, Yamamura, Yuko, Neslund-Dudas, Christine, Haslag-Minoff, Jennifer, Wu, William, Thomas, Venetta, Allen, Glenn O, Murphy, Adam, Chang, Bao-Li, Zheng, S Lilly, Leske, M Cristina, Wu, Suh-Yuh, Ray, Anna M, Hennis, Anselm JM, Thun, Michael J, Carpten, John, Casey, Graham, Carter, Erin N, Duarte, Edder R, Xia, Lucy Y, Sheng, Xin, Wan, Peggy, Pooler, Loreall C, Cheng, Iona, Monroe, Kristine R, Schumacher, Fredrick, Le Marchand, Loic, Kolonel, Laurence N, Chanock, Stephen J, Van Den Berg, David, Stram, Daniel O, and Henderson, Brian E

Subjects
African Americans, Male, Pair 17, Prostatic Neoplasms, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Chromosomes, Humans, Genetic Predisposition to Disease, Polymorphism, Human, Genome-Wide Association Study, Developmental Biology
Abstract

In search of common risk alleles for prostate cancer that could contribute to high rates of the disease in men of African ancestry, we conducted a genome-wide association study, with 1,047,986 SNP markers examined in 3,425 African-Americans with prostate cancer (cases) and 3,290 African-American male controls. We followed up the most significant 17 new associations from stage 1 in 1,844 cases and 3,269 controls of African ancestry. We identified a new risk variant on chromosome 17q21 (rs7210100, odds ratio per allele = 1.51, P = 3.4 × 10(-13)). The frequency of the risk allele is ∼5% in men of African descent, whereas it is rare in other populations (

Published
2011

3. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Author

Conti, David V, Darst, Burcu F, Moss, Lilit C, Saunders, Edward J, Sheng, Xin, Chou, Alisha, Schumacher, Fredrick R, Olama, Ali Amin Al, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N, Sahimi, Ali, Hoffmann, Thomas J, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Muir, Kenneth, Lophatananon, Artitaya, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne R, Stevens, Victoria L, Gapstur, Susan M, Carter, Brian D, Schleutker, Johanna, Tammela, Teuvo LJ, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G, Southey, Melissa C, MacInnis, Robert J, Cybulski, Cezary, Wokołorczyk, Dominika, Lubiński, Jan, Neal, David E, Donovan, Jenny L, Hamdy, Freddie C, Martin, Richard M, Nordestgaard, Børge G, Nielsen, Sune F, Weischer, Maren, Bojesen, Stig E, Røder, Martin Andreas, Iversen, Peter, Batra, Jyotsna, Chambers, Suzanne, Moya, Leire, Horvath, Lisa, Clements, Judith A, Tilley, Wayne, Risbridger, Gail P, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordström, Tobias, Pashayan, Nora, Dunning, Alison M, Ghoussaini, Maya, Travis, Ruth C, Key, Tim J, Riboli, Elio, Park, Jong Y, Sellers, Thomas A, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie J, Mucci, Lorelei A, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David J, Penney, Kathryn L, Turman, Constance, Tangen, Catherine M, Goodman, Phyllis J, Thompson, Ian M, Hamilton, Robert J, Fleshner, Neil E, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet L, Ostrander, Elaine A, Geybels, Milan S, Koutros, Stella, Freeman, Laura E Beane, Stampfer, Meir, Wolk, Alicja, Håkansson, Niclas, Andriole, Gerald L, Hoover, Robert N, Machiela, Mitchell J, Sørensen, Karina Dalsgaard, Borre, Michael, Blot, William J, Zheng, Wei, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Zhang, Hong-Wei, Feng, Ninghan, Mao, Xueying, Wu, Yudong, Zhao, Shan-Chao, Sun, Zan, Thibodeau, Stephen N, McDonnell, Shannon K, Schaid, Daniel J, West, Catharine ML, Burnet, Neil, Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S, Drake, Bettina F, Cussenot, Olivier, Cancel-Tassin, Géraldine, Menegaux, Florence, Truong, Thérèse, Koudou, Yves Akoli, John, Esther M, Grindedal, Eli Marie, Maehle, Lovise, Khaw, Kay-Tee, Ingles, Sue A, Stern, Mariana C, Vega, Ana, Gómez-Caamaño, Antonio, Fachal, Laura, Rosenstein, Barry S, Kerns, Sarah L, Ostrer, Harry, Teixeira, Manuel R, Paulo, Paula, Brandão, Andreia, Watya, Stephen, Lubwama, Alexander, Bensen, Jeannette T, Fontham, Elizabeth TH, Mohler, James, Taylor, Jack A, Kogevinas, Manolis, Llorca, Javier, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C, Huff, Chad D, Strom, Sara S, Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J, Weaver, Brandi, Brenner, Hermann, Cuk, Katarina, Holleczek, Bernd, Saum, Kai-Uwe, Klein, Eric A, Hsing, Ann W, Kittles, Rick A, Murphy, Adam B, Logothetis, Christopher J, Kim, Jeri, Neuhausen, Susan L, Steele, Linda, Ding, Yuan Chun, Isaacs, William B, Nemesure, Barbara, Hennis, Anselm JM, Carpten, John, Pandha, Hardev, Michael, Agnieszka, De Ruyck, Kim, De Meerleer, Gert, Ost, Piet, Xu, Jianfeng, Razack, Azad, Lim, Jasmine, Teo, Soo-Hwang, Newcomb, Lisa F, Lin, Daniel W, Fowke, Jay H, Neslund-Dudas, Christine, Rybicki, Benjamin A, Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Singhal, Sandeep, Parliament, Matthew, Claessens, Frank, Joniau, Steven, Van Den Broeck, Thomas, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Martinez, Maria Elena, Larkin, Samantha, Townsend, Paul A, Aukim-Hastie, Claire, Bush, William S, Aldrich, Melinda C, Crawford, Dana C, Srivastava, Shiv, Cullen, Jennifer C, Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J, Jenster, Guido, Van Schaik, Ron HN, Hu, Jennifer J, Sanderson, Maureen, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Mancuso, Nicholas, Berndt, Sonja I, Van Den Eeden, Stephen K, Easton, Douglas F, Chanock, Stephen J, Cook, Michael B, Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S, Eeles, Rosalind A, Kote-Jarai, Zsofia, and Haiman, Christopher A

Subjects
Male, Genetic Loci, Risk Factors, Racial Groups, Odds Ratio, Humans, Prostatic Neoplasms, Genetic Predisposition to Disease, Molecular Sequence Annotation, Neoplasm Invasiveness, Middle Aged, 3. Good health, Genome-Wide Association Study
Abstract

Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

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