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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. 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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8. 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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9. 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

11. 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

14. 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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16. 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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18. 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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19. 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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24. Association of Anthropometric Measures With the Risk of Prostate Cancer in the Multiethnic Cohort.

Author

Sattayapiwat, Olivia, Wan, Peggy, Hernandez, Brenda Y, Marchand, Loic Le, Wilkens, Lynne, and Haiman, Christopher A

Subjects
*OBESITY risk factors, *DISEASE progression, *STATURE, *CONFIDENCE intervals, *BODY weight, *ANTHROPOMETRY, *BLACK people, *RACE, *RISK assessment, *COMPARATIVE studies, *WAIST-hip ratio, *WAIST circumference, *DESCRIPTIVE statistics, *ETHNIC groups, *WHITE people, *ODDS ratio, *PROSTATE-specific antigen, *BODY mass index, *DATA analysis software, *PROSTATE tumors, *LONGITUDINAL method, *BODY size, *PROPORTIONAL hazards models, *TUMOR grading, *DISEASE risk factors
Abstract

In studies of anthropometric measures and prostate cancer risk, conducted primarily in White men, positive associations with advanced disease have been reported. We assessed body size in relation to incident prostate cancer risk in 79,950 men from the Multiethnic Cohort, with 8,819 cases identified over 22 years (1993–2015). Height was associated with increased risk of advanced prostate cancer (≥68 inches (≥ 173 cm) vs. < 66 inches (168 cm); hazard ratio (HR) = 1.24, 95% confidence interval (CI): 1.04, 1.48) and high-grade disease (HR = 1.15, 95% CI: 1.02, 1.31). Compared with men of normal weight, men overweight at baseline were at higher risk of high-grade cancer (HR = 1.15, 95% CI: 1.04, 1.26). Greater weight was positively associated with localized and low-grade disease in Blacks and Native Hawaiians (by race, P for heterogeneity = 0.0002 and 0.008, respectively). Weight change since age 21 years was positively associated with high-grade disease (for ≥ 40 pounds (18 kg) vs. 10 pounds (4.5 kg), HR = 1.20, 95% CI: 1.05, 1.37; P for trend  =  0.005). Comparing highest versus lowest quartile, waist-to-hip ratio was associated with a 1.78-fold increase (95% CI: 1.28, 2.46) in the risk of advanced prostate cancer. Positive associations with the majority of anthropometric measures were observed in all 5 racial/ethnic groups, suggesting a general impact of anthropometric measures on risk across populations. [ABSTRACT FROM AUTHOR]

Published
2021
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25. Evaluating Approaches for Constructing Polygenic Risk Scores for Prostate Cancer in Men of African and European Ancestry.

Author

Darst BF, Shen J, Madduri RK, Rodriguez AA, Xiao Y, Sheng X, Saunders EJ, Dadaev T, Brook MN, Hoffmann TJ, Muir K, Wan P, Le Marchand L, Wilkens L, Wang Y, Schleutker J, MacInnis RJ, Cybulski C, Neal DE, Nordestgaard BG, Nielsen SF, Batra J, Clements JA, Grönberg H, Pashayan N, Travis RC, Park JY, Albanes D, Weinstein S, Mucci LA, Hunter DJ, Penney KL, Tangen CM, Hamilton RJ, Parent MÉ, Stanford JL, Koutros S, Wolk A, Sørensen KD, Blot WJ, Yeboah ED, Mensah JE, Lu YJ, Schaid DJ, Thibodeau SN, West CM, Maier C, Kibel AS, Cancel-Tassin G, Menegaux F, John EM, Grindedal EM, Khaw KT, Ingles SA, Vega A, Rosenstein BS, Teixeira MR, Kogevinas M, Cannon-Albright L, Huff C, Multigner L, Kaneva R, Leach RJ, Brenner H, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Neuhausen SL, Isaacs WB, Nemesure B, Hennis AJ, Carpten J, Pandha H, De Ruyck K, Xu J, Razack A, Teo SH, Newcomb LF, Fowke JH, Neslund-Dudas C, Rybicki BA, Gamulin M, Usmani N, Claessens F, GagoDominguez M, Castelao JE, Townsend PA, Crawford DC, Petrovics G, Casey G, Roobol MJ, Hu JF, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Witte JS, Eeles RA, Kote-Jarai Z, Watya S, Gaziano JM, Justice AC, Conti DV, and Haiman CA

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
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