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1. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

Author

Wang, Anqi, Shen, Jiayi, Rodriguez, Alex, Saunders, Edward, Chen, Fei, Janivara, Rohini, Darst, Burcu, Sheng, Xin, Xu, Yili, Chou, Alisha, Benlloch, Sara, Dadaev, Tokhir, Brook, Mark, Plym, Anna, Sahimi, Ali, Hoffman, Thomas, Takahashi, Atushi, Matsuda, Koichi, Momozawa, Yukihide, Fujita, Masashi, Laisk, Triin, Figuerêdo, Jéssica, Muir, Kenneth, Ito, Shuji, Liu, Xiaoxi, Uchio, Yuji, Kubo, Michiaki, Kamatani, Yoichiro, Lophatananon, Artitaya, Wan, Peggy, Andrews, Caroline, Lori, Adriana, Choudhury, Parichoy, Schleutker, Johanna, Tammela, Teuvo, Sipeky, Csilla, Auvinen, Anssi, Giles, Graham, Southey, Melissa, MacInnis, Robert, Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher, Cho, Kelly, Mcmahon, Benjamin, Neal, David, Donovan, Jenny, Hamdy, Freddie, Martin, Richard, Nordestgaard, Borge, Nielsen, Sune, Weischer, Maren, Bojesen, Stig, Røder, Andreas, Stroomberg, Hein, Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith, Tilly, Wayne, Risbridger, Gail, Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, Tobias, Pashayan, Nora, Dunning, Alison, Ghoussaini, Maya, Travis, Ruth, Key, Tim, Riboli, Elio, Park, Jong, Sellers, Thomas, Lin, Hui-Yi, Albanes, Demetrius, Weinstein, Stephanie, Cook, Michael, Mucci, Lorelei, Giovannucci, Edward, Lindstrom, Sara, Kraft, Peter, Hunter, David, Penney, Kathryn, Turman, Constance, Tangen, Catherine, Goodman, Phyllis, Thompson, Ian, Hamilton, Robert, Fleshner, Neil, Finelli, Antonio, Parent, Marie-Élise, Stanford, Janet, Ostrander, Elaine, Koutros, Stella, Beane Freeman, Laura, Stampfer, Meir, Wolk, Alicja, and Håkansson, Niclas

Subjects
Humans, Male, Black People, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk Factors, White People, Asian People
Abstract

The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.

Published
2023

2. Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry

Author

Chen, Fei, Madduri, Ravi K., Rodriguez, Alex A., Darst, Burcu F., Chou, Alisha, Sheng, Xin, Wang, Anqi, Shen, Jiayi, Saunders, Edward J., Rhie, Suhn K., Bensen, Jeannette T., Ingles, Sue A., Kittles, Rick A., Strom, Sara S., Rybicki, Benjamin A., Nemesure, Barbara, Isaacs, William B., Stanford, Janet L., Zheng, Wei, Sanderson, Maureen, John, Esther M., Park, Jong Y., Xu, Jianfeng, Wang, Ying, Berndt, Sonja I., Huff, Chad D., Yeboah, Edward D., Tettey, Yao, Lachance, Joseph, Tang, Wei, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A., Yamoah, Kosj, Murphy, Adam B., Crawford, Dana C., Patel, Alpa V., Bush, William S., Aldrich, Melinda C., Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine M., Stern, Mariana C., Kote-Jarai, Zsofia, Govindasami, Koveela, Cook, Michael B., Chokkalingam, Anand P., Hsing, Ann W., Goodman, Phyllis J., Hoffmann, Thomas J., Drake, Bettina F., Hu, Jennifer J., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Idowu, Michael O., Popoola, Olufemi, Adebiyi, Akindele O., Aisuodionoe-Shadrach, Oseremen I., Ajibola, Hafees O., Jamda, Mustapha A., Oluwole, Olabode P., Nwegbu, Maxwell, Adusei, Ben, Mante, Sunny, Darkwa-Abrahams, Afua, Mensah, James E., Diop, Halimatou, Van Den Eeden, Stephen K., Blanchet, Pascal, Fowke, Jay H., Casey, Graham, Hennis, Anselm J., Lubwama, Alexander, Thompson, Ian M., Jr., Leach, Robin, Easton, Douglas F., Preuss, Michael H., Loos, Ruth J., Gundell, Susan M., Wan, Peggy, Mohler, James L., Fontham, Elizabeth T., Smith, Gary J., Taylor, Jack A., Srivastava, Shiv, Eeles, Rosaline A., Carpten, John D., Kibel, Adam S., Multigner, Luc, Parent, Marie-Élise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A., Andrews, Caroline, Rebbeck, Timothy R., Brureau, Laurent, Ambs, Stefan, Edwards, Todd L., Watya, Stephen, Chanock, Stephen J., Witte, John S., Blot, William J., Michael Gaziano, J., Justice, Amy C., Conti, David V., and Haiman, Christopher A.

Published
2023
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5. Supplementary Figure 1 from Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Author

Hughley, Raymond W., primary, Matejcic, Marco, primary, Song, Ziwei, primary, Sheng, Xin, primary, Wan, Peggy, primary, Xia, Lucy, primary, Hart, Steven N., primary, Hu, Chunling, primary, Yadav, Siddhartha, primary, Lubmawa, Alexander, primary, Kiddu, Vicky, primary, Asiimwe, Frank, primary, Amanya, Colline, primary, Mutema, George, primary, Job, Kuteesa, primary, Ssebakumba, Mbaaga K., primary, Ingles, Sue A., primary, Hamilton, Ann S., primary, Couch, Fergus J., primary, Watya, Stephen, primary, Conti, David V., primary, Darst, Burcu F., primary, and Haiman, Christopher A., primary

Published
2023
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6. Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

Author

Conti, David V, Wang, Kan, Sheng, Xin, Bensen, Jeannette T, Hazelett, Dennis J, Cook, Michael B, Ingles, Sue A, Kittles, Rick A, Strom, Sara S, Rybicki, Benjamin A, Nemesure, Barbara, Isaacs, William B, Stanford, Janet L, Zheng, Wei, Sanderson, Maureen, John, Esther M, Park, Jong Y, Xu, Jianfeng, Stevens, Victoria L, Berndt, Sonja I, Huff, Chad D, Wang, Zhaoming, Yeboah, Edward D, Tettey, Yao, Biritwum, Richard B, Adjei, Andrew A, Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Sellers, Thomas A, Yamoah, Kosj, Murphy, Adam B, Crawford, Dana C, Gapstur, Susan M, Bush, William S, Aldrich, Melinda C, Cussenot, Olivier, Petrovics, Gyorgy, Cullen, Jennifer, Neslund-Dudas, Christine, Stern, Mariana C, Jarai, Zsofia-Kote, Govindasami, Koveela, Chokkalingam, Anand P, Hsing, Ann W, Goodman, Phyllis J, Hoffmann, Thomas, Drake, Bettina F, Hu, Jennifer J, Clark, Peter E, Van Den Eeden, Stephen K, Blanchet, Pascal, Fowke, Jay H, Casey, Graham, Hennis, Anselm JM, Han, Ying, Lubwama, Alexander, Thompson, Ian M, Leach, Robin, Easton, Douglas F, Schumacher, Fredrick, Van den Berg, David J, Gundell, Susan M, Stram, Alex, Wan, Peggy, Xia, Lucy, Pooler, Loreall C, Mohler, James L, Fontham, Elizabeth TH, Smith, Gary J, Taylor, Jack A, Srivastava, Shiv, Eeles, Rosalind A, Carpten, John, Kibel, Adam S, Multigner, Luc, Parent, Marie-Elise, Menegaux, Florence, Cancel-Tassin, Geraldine, Klein, Eric A, Brureau, Laurent, Stram, Daniel O, Watya, Stephen, Chanock, Stephen J, Witte, John S, Blot, William J, Henderson, Brian E, and Haiman, Christopher A

Subjects
Aging, Human Genome, Cancer, Prevention, Prostate Cancer, Biotechnology, Clinical Research, Genetics, Urologic Diseases, 2.1 Biological and endogenous factors, Aetiology, Blacks, Case-Control Studies, Checkpoint Kinase 2, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 22, Gene Frequency, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms, PRACTICAL/ELLIPSE Consortium, Black People, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2.2%, odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.37 to 1.76, P = 6.10 × 10-12; 22q12.1: rs78554043, risk allele frequency = 1.5%, OR = 1.62, 95% CI = 1.39 to 1.89, P = 7.50 × 10-10). At 13q34, the signal is located 5' of the gene IRS2 and 3' of a long noncoding RNA, while at 22q12 the candidate functional allele is a missense variant in the CHEK2 gene. These findings provide further support for the role of ancestry-specific germline variation in contributing to population differences in prostate cancer risk.

Published
2017

7. 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 L. J., 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, Jr., 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 M. L., 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 T. H., 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 J. M., 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 H. N., 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.

Published
2021
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8. Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry

Author

Hughley, Raymond W., primary, Matejcic, Marco, additional, Song, Ziwei, additional, Sheng, Xin, additional, Wan, Peggy, additional, Xia, Lucy, additional, Hart, Steven N., additional, Hu, Chunling, additional, Yadav, Siddhartha, additional, Lubwama, Alexander, additional, Kiddu, Vicky, additional, Asiimwe, Frank, additional, Amanya, Colline, additional, Mutema, George, additional, Job, Kuteesa, additional, Ssebakumba, Mbaaga Kigongo, additional, Ingles, Sue Ann, additional, Hamilton, Ann S, additional, Couch, Fergus J, additional, Watya, Stephen, additional, Conti, David V., additional, Darst, Burcu F, additional, and Haiman, Christopher A, additional

Published
2023
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10. Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Author

Darst, Burcu F., primary, Shen, Jiayi, additional, Madduri, Ravi K., additional, Rodriguez, Alexis A., additional, Xiao, Yukai, additional, Sheng, Xin, additional, Saunders, Edward J., additional, Dadaev, Tokhir, additional, Brook, Mark N., additional, Hoffmann, Thomas J., additional, Muir, Kenneth, additional, Wan, Peggy, additional, Le Marchand, Loic, additional, Wilkens, Lynne, additional, Wang, Ying, additional, Schleutker, Johanna, additional, MacInnis, Robert J., additional, Cybulski, Cezary, additional, Neal, David E., additional, Nordestgaard, Børge G., additional, Nielsen, Sune F., additional, Batra, Jyotsna, additional, Clements, Judith A., additional, Cancer BioResource, Australian Prostate, additional, Grönberg, Henrik, additional, Pashayan, Nora, additional, Travis, Ruth C., additional, Park, Jong Y., additional, Albanes, Demetrius, additional, Weinstein, Stephanie, additional, Mucci, Lorelei A., additional, Hunter, David J., additional, Penney, Kathryn L., additional, Tangen, Catherine M., additional, Hamilton, Robert J., additional, Parent, Marie-Élise, additional, Stanford, Janet L., additional, Koutros, Stella, additional, Wolk, Alicja, additional, Sørensen, Karina D., additional, Blot, William J., additional, Yeboah, Edward D., additional, Mensah, James E., additional, Lu, Yong-Jie, additional, Schaid, Daniel J., additional, Thibodeau, Stephen N., additional, West, Catharine M., additional, Maier, Christiane, additional, Kibel, Adam S., additional, Cancel-Tassin, Géraldine, additional, Menegaux, Florence, additional, John, Esther M., additional, Grindedal, Eli Marie, additional, Khaw, Kay-Tee, additional, Ingles, Sue A., additional, Vega, Ana, additional, Rosenstein, Barry S., additional, Teixeira, Manuel R., additional, Kogevinas, Manolis, additional, Cannon-Albright, Lisa, additional, Huff, Chad, additional, Multigner, Luc, additional, Kaneva, Radka, additional, Leach, Robin J., additional, Brenner, Hermann, additional, Hsing, Ann W., additional, Kittles, Rick A., additional, Murphy, Adam B., additional, Logothetis, Christopher J., additional, Neuhausen, Susan L., additional, Isaacs, William B., additional, Nemesure, Barbara, additional, Hennis, Anselm J., additional, Carpten, John, additional, Pandha, Hardev, additional, De Ruyck, Kim, additional, Xu, Jianfeng, additional, Razack, Azad, additional, Teo, Soo-Hwang, additional, Newcomb, Lisa F., additional, Fowke, Jay H., additional, Neslund-Dudas, Christine, additional, Rybicki, Benjamin A., additional, Gamulin, Marija, additional, Usmani, Nawaid, additional, Claessens, Frank, additional, Gago-Dominguez, Manuela, additional, Castelao, Jose Esteban, additional, Townsend, Paul A., additional, Crawford, Dana C., additional, Petrovics, Gyorgy, additional, Casey, Graham, additional, Roobol, Monique J., additional, Hu, Jennifer F., additional, Berndt, Sonja I., additional, Van Den Eeden, Stephen K., additional, Easton, Douglas F., additional, Chanock, Stephen J., additional, Cook, Michael B., additional, Wiklund, Fredrik, additional, Witte, John S., additional, Eeles, Rosalind A., additional, Kote-Jarai, Zsofia, additional, Watya, Stephen, additional, Gaziano, John M., additional, Justice, Amy C., additional, Conti, David V., additional, and Haiman, Christopher A., additional

Published
2023
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11. Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study

Author

Fesinmeyer, Megan D, Meigs, James B, North, Kari E, Schumacher, Fredrick R, Bůžková, Petra, Franceschini, Nora, Haessler, Jeffrey, Goodloe, Robert, Spencer, Kylee L, Voruganti, Venkata, Howard, Barbara V, Jackson, Rebecca, Kolonel, Laurence N, Liu, Simin, Manson, JoAnn E, Monroe, Kristine R, Mukamal, Kenneth, Dilks, Holli H, Pendergrass, Sarah A, Nato, Andrew, Wan, Peggy, Wilkens, Lynne R, Marchand, Loic, Ambite, José, Buyske, Steven, Florez, Jose C, Crawford, Dana C, Hindorff, Lucia A, Haiman, Christopher A, Peters, Ulrike, and Pankow, James S

Abstract

Abstract Background Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S. Methods As part of the 'Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites. Results Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 × 10-15), versus 3/9 in AA (p= 0.03 to 6 × 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only. Conclusions Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium.

Published
2013

12. Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Author

Darst, Burcu F, Shen, Jiayi, Madduri, Ravi K, Rodriguez, Alexis A, Xiao, Yukai, Sheng, Xin, Saunders, Edward J, Dadaev, Tokhir, Brook, Mark N, Hoffmann, Thomas J, Muir, Kenneth, Wan, Peggy, Le Marchand, Loic, Wilkens, Lynne, Wang, Ying, Schleutker, Johanna, MacInnis, Robert J, Cybulski, Cezary, Neal, David E, Nordestgaard, Børge G, Nielsen, Sune F, Batra, Jyotsna, Clements, Judith A, Cancer BioResource, Australian Prostate, Grönberg, Henrik, Pashayan, Nora, Travis, Ruth C, Park, Jong Y, Albanes, Demetrius, Weinstein, Stephanie, Mucci, Lorelei A, Hunter, David J, Penney, Kathryn L, Tangen, Catherine M, Hamilton, Robert J, Parent, Marie-Élise, Stanford, Janet L, Koutros, Stella, Wolk, Alicja, Sørensen, Karina D, Blot, William J, Yeboah, Edward D, Mensah, James E, Lu, Yong-Jie, Schaid, Daniel J, Thibodeau, Stephen N, West, Catharine M, Maier, Christiane, Kibel, Adam S, and Cancel-Tassin, Géraldine

Subjects
Male, Prostatic Neoplasms/genetics, Risk Factors, Humans, Black People/genetics, Genetic Predisposition to Disease, Multifactorial Inheritance/genetics, Genome-Wide Association Study
Abstract

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635-0.677) in African and 0.844 (95% CI = 0.840-0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67-2.00) and 2.19 (95% CI = 2.14-2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659-0.700 and AUC = 0.845, 95% CI = 0.841-0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87-2.26 and OR = 2.21, 95% CI = 2.16-2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.

Published
2023

13. 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, Berg, David Van Den, Stram, Daniel O, and Henderson, Brian E

Subjects
Biological Sciences, Genetics, Human Genome, Aging, Urologic Diseases, Prevention, Prostate Cancer, Cancer, 2.1 Biological and endogenous factors, Aetiology, Black or African American, Chromosomes, Human, Pair 17, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational 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

16. Supplementary Table 1 from Evaluating Genetic Risk for Prostate Cancer among Japanese and Latinos

Author

Cheng, Iona, primary, Chen, Gary K., primary, Nakagawa, Hidewaki, primary, He, Jing, primary, Wan, Peggy, primary, Laurie, Cathy C., primary, Shen, Jess, primary, Sheng, Xin, primary, Pooler, Loreall C., primary, Crenshaw, Andrew T., primary, Mirel, Daniel B., primary, Takahashi, Atsushi, primary, Kubo, Michiaki, primary, Nakamura, Yusuke, primary, Al Olama, Ali Amin, primary, Benlloch, Sara, primary, Donovan, Jenny L., primary, Guy, Michelle, primary, Hamdy, Freddie C., primary, Kote-Jarai, Zsofia, primary, Neal, David E., primary, Wilkens, Lynne R., primary, Monroe, Kristine R., primary, Stram, Daniel O., primary, Muir, Kenneth, primary, Eeles, Rosalind A., primary, Easton, Douglas F., primary, Kolonel, Laurence N., primary, Henderson, Brian E., primary, Le Marchand, Loïc, primary, and Haiman, Christopher A., primary

Published
2023
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20. Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry

Author

Darst, Burcu F., Shen, Jiayi, Madduri, Ravi K., Rodriguez, Alexis A., Xiao, Yukai, Sheng, Xin, Saunders, Edward J., Dadaev, Tokhir, Brook, Mark N., Hoffmann, Thomas J., Muir, Kenneth, Wan, Peggy, Marchand, Loic Le, Wilkens, Lynne, Wang, Ying, Schleutker, Johanna, MacInnis, Robert J., Cybulski, Cezary, Neal, David E., G. Nordestgaard, Børge, Nielsen, Sune F., Batra, Jyotsna, Clements, Judith A., Grönberg, Henrik, Pashayan, Nora, Travis, Ruth C., Park, Jong Y., Albanes, Demetrius, Weinstein, Stephanie, Mucci, Lorelei A., Hunter, David J., Penney, Kathryn L., Tangen, Catherine M., Hamilton, Robert J., Parent, Marie-Élise, Stanford, Janet L., Koutros, Stella, Wolk, Alicja, Sørensen, Karina D., Blot, William J., Yeboah, Edward D., Mensah, James E., Lu, Yong-Jie, Schaid, Daniel J., Thibodeau, Stephen N., West, Catharine M., Maier, Christiane, Kibel, Adam S., Cancel-Tassin, Géraldine, Menegaux, Florence, John, Esther M., Grindedal, Eli Marie, Khaw, Kay-Tee, Ingles, Sue A., Vega, Ana, Rosenstein, Barry S., Teixeira, Manuel R., Kogevinas, Manolis, Cannon-Albright, Lisa, Huff, Chad, Multigner, Luc, Kaneva, Radka, Leach, Robin J., Brenner, Hermann, Hsing, Ann W., Kittles, Rick A., Murphy, Adam B., Logothetis, Christopher J., Neuhausen, Susan L., Isaacs, William B., Nemesure, Barbara, Hennis, Anselm J., Carpten, John, Pandha, Hardev, De Ruyck, Kim, Xu, Jianfeng, Razack, Azad, Teo, Soo-Hwang, Newcomb, Lisa F., Fowke, Jay H., Neslund-Dudas, Christine, Rybicki, Benjamin A., Gamulin, Marija, Usmani, Nawaid, Claessens, Frank, Gago-Dominguez, Manuela, Castelao, Jose Esteban, Townsend, Paul A., Crawford, Dana C., Petrovics, Gyorgy, Casey, Graham, Roobol, Monique J., Hu, Jennifer F., Berndt, Sonja I., Van Den Eeden, Stephen K., Easton, Douglas F., Chanock, Stephen J., Cook, Michael B., Wiklund, Fredrik, Witte, John S., Eeles, Rosalind A., Kote-Jarai, Zsofia, Watya, Stephen, Gaziano, John M., Justice, Amy C., Conti, David V., and Haiman, Christopher A.

Subjects
Article
Abstract

Genome-wide polygenic risk scores (GW-PRS) have been reported to have better predictive ability than PRS based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer risk variants from multi-ancestry GWAS and fine-mapping studies (PRS (269) ). GW-PRS models were trained using a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls used to develop the multi-ancestry PRS (269) . Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California/Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI=0.635-0.677) in African and 0.844 (95% CI=0.840-0.848) in European ancestry men and corresponding prostate cancer OR of 1.83 (95% CI=1.67-2.00) and 2.19 (95% CI=2.14-2.25), respectively, for each SD unit increase in the GW-PRS. However, compared to the GW-PRS, in African and European ancestry men, the PRS (269) had larger or similar AUCs (AUC=0.679, 95% CI=0.659-0.700 and AUC=0.845, 95% CI=0.841-0.849, respectively) and comparable prostate cancer OR (OR=2.05, 95% CI=1.87-2.26 and OR=2.21, 95% CI=2.16-2.26, respectively). Findings were similar in the validation data. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the multi-ancestry PRS (269) constructed with fine-mapping.

Published
2023

23. Publisher Correction: 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 L. J., 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, Jr., 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 M. L., 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 T. H., 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 J. M., 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 H. N., 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.

Published
2021
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24. Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men

Author

Wang, Anqi, primary, Xu, Yili, additional, Yu, Yao, additional, Nead, Kevin T, additional, Kim, TaeBeom, additional, Xu, Keren, additional, Dadaev, Tokhir, additional, Saunders, Ed, additional, Sheng, Xin, additional, Wan, Peggy, additional, Pooler, Loreall, additional, Xia, Lucy Y, additional, Chanock, Stephen, additional, Berndt, Sonja I, additional, Gapstur, Susan M, additional, Stevens, Victoria, additional, Albanes, Demetrius, additional, Weinstein, Stephanie J, additional, Gnanapragasam, Vincent, additional, Giles, Graham G, additional, Nguyen-Dumont, Tu, additional, Milne, Roger L, additional, Pomerantz, Mark M, additional, Schmidt, Julie A, additional, Stopsack, Konrad H, additional, Mucci, Lorelei A, additional, Catalona, William J, additional, Hetrick, Kurt N, additional, Doheny, Kimberly F, additional, MacInnis, Robert J, additional, Southey, Melissa C, additional, Eeles, Rosalind A, additional, Wiklund, Fredrik, additional, Kote-Jarai, Zsofia, additional, de Smith, Adam J, additional, Conti, David V, additional, Huff, Chad, additional, Haiman, Christopher A, additional, and Darst, Burcu F, additional

Published
2022
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26. Abstract 688: Multi-stage exome sequencing study of 17,546 aggressive and non-aggressive prostate cancer cases

Author

Darst, Burcu F., primary, Saunders, Ed, additional, Dadaev, Tokhir, additional, Sheng, Xin, additional, Wan, Peggy, additional, Pooler, Loreall, additional, Xia, Lucy Y., additional, Chanock, Stephen, additional, Berndt, Sonja I., additional, Gapstur, Susan M., additional, Stevens, Victoria, additional, Albanes, Demetrius, additional, Weinstein, Stephanie J., additional, Gnanapragasam, Vincent, additional, Giles, Graham G., additional, Nguyen-Dumont, Tu, additional, Milne, Roger L., additional, Pomerantz, Mark M., additional, Schmidt, Julie A., additional, Travis, Ruth C., additional, Key, Timothy J., additional, Stopsack, Konrad H., additional, Mucci, Lorelei A., additional, Catalona, William J., additional, Marosy, Beth, additional, Hetrick, Kurt N., additional, Doheny, Kimberly F., additional, MacInnis, Robert J., additional, Southey, Melissa C., additional, Eeles, Rosalind A., additional, Wiklund, Fredrik, additional, Kote-Jarai, Zsofia, additional, Conti, David V., additional, and Haiman, Christopher A., additional

Published
2022
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27. A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry

Author

Darst, Burcu F., primary, Hughley, Raymond, additional, Pfennig, Aaron, additional, Hazra, Ujani, additional, Fan, Caoqi, additional, Wan, Peggy, additional, Sheng, Xin, additional, Xia, Lucy, additional, Andrews, Caroline, additional, Chen, Fei, additional, Berndt, Sonja I., additional, Kote-Jarai, Zsofia, additional, Govindasami, Koveela, additional, Bensen, Jeannette T., additional, Ingles, Sue A., additional, Rybicki, Benjamin A., additional, Nemesure, Barbara, additional, John, Esther M., additional, Fowke, Jay H., additional, Huff, Chad D., additional, Strom, Sara S., additional, Isaacs, William B., additional, Park, Jong Y., additional, Zheng, Wei, additional, Ostrander, Elaine A., additional, Walsh, Patrick C., additional, Carpten, John, additional, Sellers, Thomas A., additional, Yamoah, Kosj, additional, Murphy, Adam B., additional, Sanderson, Maureen, additional, Crawford, Dana C., additional, Gapstur, Susan M., additional, Bush, William S., additional, Aldrich, Melinda C., additional, Cussenot, Olivier, additional, Petrovics, Gyorgy, additional, Cullen, Jennifer, additional, Neslund-Dudas, Christine, additional, Kittles, Rick A., additional, Xu, Jianfeng, additional, Stern, Mariana C., additional, Chokkalingam, Anand P., additional, Multigner, Luc, additional, Parent, Marie-Elise, additional, Menegaux, Florence, additional, Cancel-Tassin, Geraldine, additional, Kibel, Adam S., additional, Klein, Eric A., additional, Goodman, Phyllis J., additional, Stanford, Janet L., additional, Drake, Bettina F., additional, Hu, Jennifer J., additional, Clark, Peter E., additional, Blanchet, Pascal, additional, Casey, Graham, additional, Hennis, Anselm J.M., additional, Lubwama, Alexander, additional, Thompson, Ian M., additional, Leach, Robin J., additional, Gundell, Susan M., additional, Pooler, Loreall, additional, Mohler, James L., additional, Fontham, Elizabeth T.H., additional, Smith, Gary J., additional, Taylor, Jack A., additional, Brureau, Laurent, additional, Blot, William J., additional, Biritwum, Richard, additional, Tay, Evelyn, additional, Truelove, Ann, additional, Niwa, Shelley, additional, Tettey, Yao, additional, Varma, Rohit, additional, McKean-Cowdin, Roberta, additional, Torres, Mina, additional, Jalloh, Mohamed, additional, Magueye Gueye, Serigne, additional, Niang, Lamine, additional, Ogunbiyi, Olufemi, additional, Oladimeji Idowu, Michael, additional, Popoola, Olufemi, additional, Adebiyi, Akindele O., additional, Aisuodionoe-Shadrach, Oseremen I., additional, Nwegbu, Maxwell, additional, Adusei, Ben, additional, Mante, Sunny, additional, Darkwa-Abrahams, Afua, additional, Yeboah, Edward D., additional, Mensah, James E., additional, Anthony Adjei, Andrew, additional, Diop, Halimatou, additional, Cook, Michael B., additional, Chanock, Stephen J., additional, Watya, Stephen, additional, Eeles, Rosalind A., additional, Chiang, Charleston W.K., additional, Lachance, Joseph, additional, Rebbeck, Timothy R., additional, Conti, David V., additional, and Haiman, Christopher A., additional

Published
2022
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32. Genome-wide association study of colorectal cancer in Hispanics

Author

Schmit, Stephanie L., Schumacher, Fredrick R., Edlund, Christopher K., Conti, David V., Ihenacho, Ugonna, Wan, Peggy, Van Den Berg, David, Casey, Graham, Fortini, Barbara K., Lenz, Heinz-Josef, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A., Moreno-Macías, Hortensia, Huerta-Chagoya, Alicia, Ordóñez-Sánchez, María Luisa, Rodríguez-Guillén, Rosario, Cruz-Bautista, Ivette, Rodríguez-Torres, Maribel, Muñóz-Hernández, Linda Liliana, Arellano-Campos, Olimpia, Gómez, Donají, Alvirde, Ulices, González-Villalpando, Clicerio, González-Villalpando, María Elena, Le Marchand, Loic, Haiman, Christopher A., and Figueiredo, Jane C.

Published
2016
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34. 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

35. A genome-wide association study of breast cancer in women of African ancestry

Author

Chen, Fang, Chen, Gary K., Stram, Daniel O., Millikan, Robert C., Ambrosone, Christine B., John, Esther M., Bernstein, Leslie, Zheng, Wei, Palmer, Julie R., Hu, Jennifer J., Rebbeck, Tim R., Ziegler, Regina G., Nyante, Sarah, Bandera, Elisa V., Ingles, Sue A., Press, Michael F., Ruiz-Narvaez, Edward A., Deming, Sandra L., Rodriguez-Gil, Jorge L., DeMichele, Angela, Chanock, Stephen J., Blot, William, Signorello, Lisa, Cai, Qiuyin, Li, Guoliang, Long, Jirong, Huo, Dezheng, Zheng, Yonglan, Cox, Nancy J., Olopade, Olufunmilayo I., Ogundiran, Temidayo O., Adebamowo, Clement, Nathanson, Katherine L., Domchek, Susan M., Simon, Michael S., Hennis, Anselm, Nemesure, Barbara, Wu, Suh-Yuh, Leske, M. Cristina, Ambs, Stefan, Hutter, Carolyn M., Young, Alicia, Kooperberg, Charles, Peters, Ulrike, Rhie, Suhn K., Wan, Peggy, Sheng, Xin, Pooler, Loreall C., Van Den Berg, David J., Le Marchand, Loic, Kolonel, Laurence N., Henderson, Brian E., and Haiman, Christopher A.

Published
2013
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37. A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry

Author

Darst, Burcu F., primary, Wan, Peggy, additional, Sheng, Xin, additional, Bensen, Jeannette T., additional, Ingles, Sue A., additional, Rybicki, Benjamin A., additional, Nemesure, Barbara, additional, John, Esther M., additional, Fowke, Jay H., additional, Stevens, Victoria L., additional, Berndt, Sonja I., additional, Huff, Chad D., additional, Strom, Sara S., additional, Park, Jong Y., additional, Zheng, Wei, additional, Ostrander, Elaine A., additional, Walsh, Patrick C., additional, Srivastava, Shiv, additional, Carpten, John, additional, Sellers, Thomas A., additional, Yamoah, Kosj, additional, Murphy, Adam B., additional, Sanderson, Maureen, additional, Crawford, Dana C., additional, Gapstur, Susan M., additional, Bush, William S., additional, Aldrich, Melinda C., additional, Cussenot, Olivier, additional, Yeager, Meredith, additional, Petrovics, Gyorgy, additional, Cullen, Jennifer, additional, Neslund-Dudas, Christine, additional, Kittles, Rick A., additional, Xu, Jianfeng, additional, Stern, Mariana C., additional, Kote-Jarai, Zsofia, additional, Govindasami, Koveela, additional, Chokkalingam, Anand P., additional, Multigner, Luc, additional, Parent, Marie-Elise, additional, Menegaux, Florence, additional, Cancel-Tassin, Geraldine, additional, Kibel, Adam S., additional, Klein, Eric A., additional, Goodman, Phyllis J., additional, Drake, Bettina F., additional, Hu, Jennifer J., additional, Clark, Peter E., additional, Blanchet, Pascal, additional, Casey, Graham, additional, Hennis, Anselm J.M., additional, Lubwama, Alexander, additional, Thompson, Ian M., additional, Leach, Robin, additional, Gundell, Susan M., additional, Pooler, Loreall, additional, Xia, Lucy, additional, Mohler, James L., additional, Fontham, Elizabeth T.H., additional, Smith, Gary J., additional, Taylor, Jack A., additional, Eeles, Rosalind A., additional, Brureau, Laurent, additional, Chanock, Stephen J., additional, Watya, Stephen, additional, Stanford, Janet L., additional, Mandal, Diptasri, additional, Isaacs, William B., additional, Cooney, Kathleen, additional, Blot, William J., additional, Conti, David V., additional, and Haiman, Christopher A., additional

Published
2020
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38. Consistent Directions of Effect for Established Type 2 Diabetes Risk Variants Across Populations: The Population Architecture using Genomics and Epidemiology (PAGE) Consortium

Author

Haiman, Christopher A., Fesinmeyer, Megan D., Spencer, Kylee L., Bůžková, Petra, Voruganti, V. Saroja, Wan, Peggy, Haessler, Jeff, Franceschini, Nora, Monroe, Kristine R., Howard, Barbara V., Jackson, Rebecca D., Florez, Jose C., Kolonel, Laurence N., Buyske, Steven, Goodloe, Robert J., Liu, Simin, Manson, JoAnn E., Meigs, James B., Waters, Kevin, Mukamal, Kenneth J., Pendergrass, Sarah A., Shrader, Peter, Wilkens, Lynne R., Hindorff, Lucia A., Ambite, Jose Luis, North, Kari E., Peters, Ulrike, Crawford, Dana C., Le Marchand, Loic, and Pankow, James S.

Published
2012
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39. Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer

Author

Darst, Burcu F, primary, Dadaev, Tokhir, additional, Saunders, Ed, additional, Sheng, Xin, additional, Wan, Peggy, additional, Pooler, Loreall, additional, Xia, Lucy Y, additional, Chanock, Stephen, additional, Berndt, Sonja I, additional, Gapstur, Susan M, additional, Stevens, Victoria, additional, Albanes, Demetrius, additional, Weinstein, Stephanie J, additional, Gnanapragasam, Vincent, additional, Giles, Graham G, additional, Nguyen-Dumont, Tu, additional, Milne, Roger L, additional, Pomerantz, Mark, additional, Schmidt, Julie A, additional, Mucci, Lorelei, additional, Catalona, William J, additional, Hetrick, Kurt N, additional, Doheny, Kimberly F, additional, MacInnis, Robert J, additional, Southey, Melissa C, additional, Eeles, Rosalind A, additional, Wiklund, Fredrik, additional, Kote-Jarai, Zsofia, additional, Conti, David V, additional, and Haiman, Christopher A, additional

Published
2020
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40. The Four-Kallikrein Panel Is Effective in Identifying Aggressive Prostate Cancer in a Multiethnic Population

Author

Darst, Burcu F., primary, Chou, Alisha, additional, Wan, Peggy, additional, Pooler, Loreall, additional, Sheng, Xin, additional, Vertosick, Emily A., additional, Conti, David V., additional, Wilkens, Lynne R., additional, Le Marchand, Loïc, additional, Vickers, Andrew J., additional, Lilja, Hans G., additional, and Haiman, Christopher A., additional

Published
2020
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41. Population-specific reference panels are crucial for genetic analyses: an example of the CREBRF locus in Native Hawaiians

Author

Lin, Meng, primary, Caberto, Christian, additional, Wan, Peggy, additional, Li, Yuqing, additional, Lum-Jones, Annette, additional, Tiirikainen, Maarit, additional, Pooler, Loreall, additional, Nakamura, Brooke, additional, Sheng, Xin, additional, Porcel, Jacqueline, additional, Lim, Unhee, additional, Setiawan, Veronica Wendy, additional, Le Marchand, Loïc, additional, Wilkens, Lynne R, additional, Haiman, Christopher A, additional, Cheng, Iona, additional, and Chiang, Charleston W K, additional

Published
2020
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44. Population specific reference panels are crucial for the genetic analyses of Native Hawai’ians: an example of theCREBRFlocus

Author

Lin, Meng, primary, Caberto, Christian, additional, Wan, Peggy, additional, Li, Yuqing, additional, Lum-Jones, Annette, additional, Tiirikainen, Maarit, additional, Pooler, Loreall, additional, Nakamura, Brooke, additional, Sheng, Xin, additional, Porcel, Jacqueline, additional, Lim, Unhee, additional, Setiawan, Veronica Wendy, additional, Marchand, Loïc Le, additional, Wilkens, Lynne R., additional, Haiman, Christopher A., additional, Cheng, Iona, additional, and Chiang, Charleston W. K., additional

Published
2019
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49. Germline Sequencing DNA Repair Genes in 5545 Men With Aggressive and Nonaggressive Prostate Cancer.

Author

Darst, Burcu F, Dadaev, Tokhir, Saunders, Ed, Sheng, Xin, Wan, Peggy, Pooler, Loreall, Xia, Lucy Y, Chanock, Stephen, Berndt, Sonja I, Gapstur, Susan M, Stevens, Victoria, Albanes, Demetrius, Weinstein, Stephanie J, Gnanapragasam, Vincent, Giles, Graham G, Nguyen-Dumont, Tu, Milne, Roger L, Pomerantz, Mark, Schmidt, Julie A, and Mucci, Lorelei

Subjects
DNA repair, GENES, HEREDITARY nonpolyposis colorectal cancer, GERM cells, PROSTATE cancer, ALLELES, BRCA genes, RESEARCH, GENETIC mutation, DNA, RESEARCH methodology, EVALUATION research, COMPARATIVE studies, DISEASE susceptibility, PROSTATE tumors
Abstract

Background: There is an urgent need to identify factors specifically associated with aggressive prostate cancer (PCa) risk. We investigated whether rare pathogenic, likely pathogenic, or deleterious (P/LP/D) germline variants in DNA repair genes are associated with aggressive PCa risk in a case-case study of aggressive vs nonaggressive disease.Methods: Participants were 5545 European-ancestry men, including 2775 nonaggressive and 2770 aggressive PCa cases, which included 467 metastatic cases (16.9%). Samples were assembled from 12 international studies and germline sequenced together. Rare (minor allele frequency < 0.01) P/LP/D variants were analyzed for 155 DNA repair genes. We compared single variant, gene-based, and DNA repair pathway-based burdens by disease aggressiveness. All statistical tests are 2-sided.Results: BRCA2 and PALB2 had the most statistically significant gene-based associations, with 2.5% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D BRCA2 alleles (odds ratio [OR] = 3.19, 95% confidence interval [CI] = 1.94 to 5.25, P = 8.58 × 10-7) and 0.65% of aggressive and 0.11% of nonaggressive cases carrying P/LP/D PALB2 alleles (OR = 6.31, 95% CI = 1.83 to 21.68, P = 4.79 × 10-4). ATM had a nominal association, with 1.6% of aggressive and 0.8% of nonaggressive cases carrying P/LP/D ATM alleles (OR = 1.88, 95% CI = 1.10 to 3.22, P = .02). In aggregate, P/LP/D alleles within 24 literature-curated candidate PCa DNA repair genes were more common in aggressive than nonaggressive cases (carrier frequencies = 14.2% vs 10.6%, respectively; P = 5.56 × 10-5). However, this difference was non-statistically significant (P = .18) on excluding BRCA2, PALB2, and ATM. Among these 24 genes, P/LP/D carriers had a 1.06-year younger diagnosis age (95% CI = -1.65 to 0.48, P = 3.71 × 10-4).Conclusions: Risk conveyed by DNA repair genes is largely driven by rare P/LP/D alleles within BRCA2, PALB2, and ATM. These findings support the importance of these genes in both screening and disease management considerations. [ABSTRACT FROM AUTHOR]

Published
2021
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