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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 A., Saunders, Edward J., Chen, Fei, Janivara, Rohini, Darst, Burcu F., Sheng, Xin, Xu, Yili, Chou, Alisha J., Benlloch, Sara, Dadaev, Tokhir, Brook, Mark N., Plym, Anna, Sahimi, Ali, Hoffman, Thomas J., 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 P., Schleutker, Johanna, Tammela, Teuvo L. J., Sipeky, Csilla, Auvinen, Anssi, Giles, Graham G., Southey, Melissa C., MacInnis, Robert J., Cybulski, Cezary, Wokolorczyk, Dominika, Lubinski, Jan, Rentsch, Christopher T., Cho, Kelly, Mcmahon, Benjamin H., Neal, David E., Donovan, Jenny L., Hamdy, Freddie C., Martin, Richard M., Nordestgaard, Borge G., Nielsen, Sune F., Weischer, Maren, Bojesen, Stig E., Røder, Andreas, Stroomberg, Hein V., Batra, Jyotsna, Chambers, Suzanne, Horvath, Lisa, Clements, Judith A., Tilly, Wayne, Risbridger, Gail P., Gronberg, Henrik, Aly, Markus, Szulkin, Robert, Eklund, Martin, Nordstrom, 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, Cook, Michael B., 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., Koutros, Stella, Beane Freeman, Laura E., 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., Barnett, Gill, Maier, Christiane, Schnoeller, Thomas, Luedeke, Manuel, Kibel, Adam S., Drake, Bettina F., Cussenot, Olivier, Cancel-Tassin, Geraldine, 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., Butler, Ebonee N., Mohler, James L., Taylor, Jack A., Kogevinas, Manolis, Dierssen-Sotos, Trinidad, Castaño-Vinyals, Gemma, Cannon-Albright, Lisa, Teerlink, Craig C., Huff, Chad D., Pilie, Patrick, Yu, Yao, Bohlender, Ryan J., Gu, Jian, Strom, Sara S., Multigner, Luc, Blanchet, Pascal, Brureau, Laurent, Kaneva, Radka, Slavov, Chavdar, Mitev, Vanio, Leach, Robin J., Brenner, Hermann, Chen, Xuechen, Holleczek, Bernd, Schöttker, Ben, 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 M., Rybicki, Benjamin A., Gamulin, Marija, Lessel, Davor, Kulis, Tomislav, Usmani, Nawaid, Abraham, Aswin, 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, Petrovics, Gyorgy, Casey, Graham, Wang, Ying, Tettey, Yao, Lachance, Joseph, Tang, Wei, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Yamoah, Kosj, Govindasami, Koveela, Chokkalingam, Anand P., Keaton, Jacob M., Hellwege, Jacklyn N., Clark, Peter E., Jalloh, Mohamed, Gueye, Serigne M., Niang, Lamine, Ogunbiyi, Olufemi, Shittu, Olayiwola, Amodu, Olukemi, 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, Diop, Halimatou, Gundell, Susan M., Roobol, Monique J., Jenster, Guido, van Schaik, Ron H. N., Hu, Jennifer J., Sanderson, Maureen, Kachuri, Linda, Varma, Rohit, McKean-Cowdin, Roberta, Torres, Mina, Preuss, Michael H., Loos, Ruth J. F., Zawistowski, Matthew, Zöllner, Sebastian, Lu, Zeyun, Van Den Eeden, Stephen K., Easton, Douglas F., Ambs, Stefan, Edwards, Todd L., Mägi, Reedik, Rebbeck, Timothy R., Fritsche, Lars, Chanock, Stephen J., Berndt, Sonja I., Wiklund, Fredrik, Nakagawa, Hidewaki, Witte, John S., Gaziano, J. Michael, Justice, Amy C., Mancuso, Nick, Terao, Chikashi, Eeles, Rosalind A., Kote-Jarai, Zsofia, Madduri, Ravi K., Conti, David V., and Haiman, Christopher A.

Published
2023
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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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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 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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7. Atopic allergic conditions and prostate cancer risk and survival in the Multiethnic Cohort study.

Author

Wang, Anqi, Wan, Peggy, Hebert, James R., Le Marchand, Loic, Wilkens, Lynne R., and Haiman, Christopher A.

Abstract

Background: Previous studies investigating relationship between atopic allergic conditions (AACs)—a highly reactive immune state—and prostate cancer (PCa) risk were inconclusive, and few have studied diverse racial/ethnic populations. Methods: We analysed 74,714 men aged ≥45 years at enrollment in Multiethnic Cohort study. Using multivariable Cox regression, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for self-reported AAC status on PCa outcomes. Results: Through 2017, 8697 incident PCa and 1170 related deaths occurred. Twenty-one percent of men reported a history of AACs. AACs were not associated with incident PCa (HR = 0.98, 95% CI: 0.93–1.03) but were significantly inversely associated with PCa mortality (HR = 0.79, 95% CI: 0.67–0.92). This inverse association was consistently observed across all racial/ethnic groups (HR range: 0.60–0.90). Among men diagnosed with PCa, AACs were inversely associated with PCa-specific death (HR = 0.75, 95% CI: 0.63–0.89). Adjusting for potential confounding effect of PSA screening did not meaningfully change the results. No significant heterogeneity was observed in the effect of AACs on PCa incidence or mortality by Dietary Inflammatory Index. Conclusions: Hyper-allergic conditions were not associated with PCa incidence but were inversely associated with PCa mortality, suggesting a potential role in reducing tumour progression. Further aetiological research is warranted to understand underlying mechanisms. [ABSTRACT FROM AUTHOR]

Published
2023
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9. 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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11. 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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13. 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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17. 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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21. 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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22. A Germline Variant at 8q24 Contributes to Familial Clustering of Prostate Cancer in Men of African Ancestry.

Author

Darst, Burcu F., Wan, Peggy, Sheng, Xin, Bensen, Jeannette T., Ingles, Sue A., Rybicki, Benjamin A., Nemesure, Barbara, John, Esther M., Fowke, Jay H., Stevens, Victoria L., Berndt, Sonja I., Huff, Chad D., Strom, Sara S., Park, Jong Y., Zheng, Wei, Ostrander, Elaine A., Walsh, Patrick C., Srivastava, Shiv, Carpten, John, and Sellers, Thomas A.

Subjects
*GENETIC mutation, *GENEALOGY, *GENETIC carriers, *GERM cells
Abstract

Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry–specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age <60 yr, the odds ratios for TA heterozygotes and TT homozygotes were 3.92 (95% confidence interval [CI] = 2.13–7.22) and 33.41 (95% CI = 10.86–102.84), respectively. Among men with a PCa family history, the absolute risk by age 60 yr reached 21% (95% CI = 17–25%) for TA heterozygotes and 38% (95% CI = 13–65%) for TT homozygotes. We estimate that in men of African ancestry, rs72725854 accounts for 32% of the total familial risk explained by all known PCa risk variants. We found that rs72725854, an African ancestry–specific risk variant, is more common in men with a family history of prostate cancer and in those diagnosed with prostate cancer at younger ages. Men of African ancestry may benefit from the knowledge of their carrier status for this genetic risk variant to guide decisions about prostate cancer screening. The African ancestry–specific prostate cancer risk variant at 8q24, rs72725854, is enriched in men diagnosed at younger ages and men with a prostate cancer family history. Carriers of this risk allele would benefit from regular and earlier prostate cancer screening. [ABSTRACT FROM AUTHOR]

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

Author

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

Abstract

Background: The four-kallikrein (4K) panel has been demonstrated to improve prediction of aggressive prostate cancer compared with prostate-specific antigen (PSA) among men with moderately elevated PSA levels. However, the development and testing of the 4K panel has been conducted primarily in White men, with limited data in African Americans and no studies in other racial and ethnic groups. Methods: We evaluated the 4K panel in a nested case-control study among African American, Latino, Japanese, Native Hawaiian, and White men in the Multiethnic Cohort. Prediagnostic blood levels of free, intact, and total PSA and human kallikrein-related peptidase 2 were measured among 1,667 incident prostate cancer cases and 691 controls with PSA =2 ng/mL. We evaluated the discriminative ability of the 4K panel within and across all racial/ethnic groups. Results: The 4K panel enhanced discrimination of overall prostate cancer compared with free plus total PSA and total PSA alone (AUC 0.748 vs. 0.711 and 0.669, respectively). Discrimination was further enhanced for Gleason 8+ prostate cancer, aggressive prostate cancer, and death due to prostate cancer, and to a lesser degree for nonaggressive prostate cancer. Improvement of the 4K panel over PSA was observed in each population. Adding a prostate cancer polygenic risk score slightly improved upon the discriminative ability of the 4K panel. Conclusions: The superior discriminative ability of the 4K panel over PSA for overall and aggressive prostate cancer across multiethnic populations indicates the broad clinical applicability of the 4K panel. [ABSTRACT FROM AUTHOR]

Published
2020
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25. Effect of Phytoestrogens from Soy Foods on Ovarian Function in Premenopausal Women

Author

Wu, Anna H., Stanczyk, Frank, Hendrich, Suzanne, Murphy, Patricia, Zhang, Chunying, Wan, Peggy, and Pike, Malcolm C.

Subjects
Soyfoods -- Health aspects, Breast cancer -- Risk factors, Estrogen -- Health aspects, Food/cooking/nutrition
Abstract

There is suggestive epidemiologic evidence that high soy intake may protect against breast cancer. The mechanisms by which intake of soy may influence risk of breast cancer are not known. A predominant hypothesis focuses on the potential effects of soy on hormone production and metabolism. The main objective of this soy intervention study was to investigate the relationship between ovarian function in healthy cycling premenopausal women and daily intake of Asian soy foods (tofu, soy milk and soybean peas). The women's hormone levels were compared during the soy intervention with their levels before and after intervention. Twenty women completed this 7-mo study, which consisted of 2 mo of baseline assessment, 3 mo of soyfood supplementation and 2 mo of follow-up assessment. During the entire study period, subjects provided morning urine specimens and blood specimens during specified days of their menstrual cycles. In addition, subjects completed a daily log to record information on menstrual cycle, alcohol intake, exercise pattern, and the amount and types of soy food eaten (during the intervention months only). Soy intervention was associated with a significant reduction in serum luteal estradiol level, but there were no significant changes in follicular phase estradiol, follicular or luteal phase progesterone, sex hormone--binding globulin or menstrual cycle length. Implications of these findings will be discussed.

Published
2000

26. Genetic risk of prostate cancer in Ugandan men.

Author

Du, Zhaohui, Lubmawa, Alexander, Gundell, Susan, Wan, Peggy, Nalukenge, Cissy, Muwanga, Proscovia, Lutalo, Moses, Nansereko, Deborah, Ndaruhutse, Olivia, Katuku, Molly, Nassanga, Rosemary, African Ancestry Prostate Cancer Consortium (AAPC), Asiimwe, Frank, Masaba, Benon, Kaggwa, Sam, Namuguzi, Dan, Kiddu, Vicky, Mutema, George, Conti, David V., and Luke, Asiimwe

Published
2018
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27. A Genome-Wide Scan for Breast Cancer Risk Haplotypes among African American Women.

Author

Song, Chi, Chen, Gary K., Millikan, Robert C., Ambrosone, Christine B., John, Esther M., Bernstein, Leslie, Zheng, Wei, Hu, Jennifer J., Ziegler, Regina G., Nyante, Sarah, Bandera, Elisa V., Ingles, Sue A., Press, Michael F., Deming, Sandra L., Rodriguez-Gil, Jorge L., Chanock, Stephen J., Wan, Peggy, Sheng, Xin, Pooler, Loreall C., and Van Den Berg, David J.

Subjects
BREAST cancer risk factors, GENOMES, SINGLE nucleotide polymorphisms, HAPLOTYPES, CANCER in women, DISEASES in African Americans, HUMAN chromosomes
Abstract

Genome-wide association studies (GWAS) simultaneously investigating hundreds of thousands of single nucleotide polymorphisms (SNP) have become a powerful tool in the investigation of new disease susceptibility loci. Haplotypes are sometimes thought to be superior to SNPs and are promising in genetic association analyses. The application of genome-wide haplotype analysis, however, is hindered by the complexity of haplotypes themselves and sophistication in computation. We systematically analyzed the haplotype effects for breast cancer risk among 5,761 African American women (3,016 cases and 2,745 controls) using a sliding window approach on the genome-wide scale. Three regions on chromosomes 1, 4 and 18 exhibited moderate haplotype effects. Furthermore, among 21 breast cancer susceptibility loci previously established in European populations, 10p15 and 14q24 are likely to harbor novel haplotype effects. We also proposed a heuristic of determining the significance level and the effective number of independent tests by the permutation analysis on chromosome 22 data. It suggests that the effective number was approximately half of the total (7,794 out of 15,645), thus the half number could serve as a quick reference to evaluating genome-wide significance if a similar sliding window approach of haplotype analysis is adopted in similar populations using similar genotype density. [ABSTRACT FROM AUTHOR]

Published
2013
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28. Reproducibility, Performance, and Clinical Utility of a Genetic Risk Prediction Model for Prostate Cancer in Japanese.

Author

Akamatsu, Shusuke, Takahashi, Atsushi, Takata, Ryo, Kubo, Michiaki, Inoue, Takahiro, Morizono, Takashi, Tsunoda, Tatsuhiko, Kamatani, Naoyuki, Haiman, Christopher A., Wan, Peggy, Chen, Gary K., Le Marchand, Loic, Kolonel, Laurence N., Henderson, Brian E., Fujioka, Tomoaki, Habuchi, Tomonori, Nakamura, Yusuke, Ogawa, Osamu, and Nakagawa, Hidewaki

Subjects
PROSTATE-specific antigen, BIOMARKERS, PROSTATE cancer, NEEDLE biopsy, PREDICTION models, LOGISTIC regression analysis
Abstract

Prostate specific antigen (PSA) is widely used as a diagnostic biomarker for prostate cancer (PC). However, due to its low predictive performance, many patients without PC suffer from the harms of unnecessary prostate needle biopsies. The present study aims to evaluate the reproducibility and performance of a genetic risk prediction model in Japanese and estimate its utility as a diagnostic biomarker in a clinical scenario. We created a logistic regression model incorporating 16 SNPs that were significantly associated with PC in a genome-wide association study of Japanese population using 689 cases and 749 male controls. The model was validated by two independent sets of Japanese samples comprising 3,294 cases and 6,281 male controls. The areas under curve (AUC) of the model were 0.679, 0.655, and 0.661 for the samples used to create the model and those used for validation. The AUCs were not significantly altered in samples with PSA 1-10 ng/ml. 24.2% and 9.7% of the patients had odds ratio <0.5 (low risk) or >2 (high risk) in the model. Assuming the overall positive rate of prostate needle biopsies to be 20%, the positive biopsy rates were 10.7% and 42.4% for the low and high genetic risk groups respectively. Our genetic risk prediction model for PC was highly reproducible, and its predictive performance was not influenced by PSA. The model could have a potential to affect clinical decision when it is applied to patients with gray-zone PSA, which should be confirmed in future clinical studies. [ABSTRACT FROM AUTHOR]

Published
2012
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29. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

Author

Al Olama, Ali Amin, Kote-Jarai, Zsofia, Berndt, Sonja I., Conti, David V., Schumacher, Fredrick, Han, Ying, Benlloch, Sara, Hazelett, Dennis J., Wang, Zhaoming, Saunders, Ed, Leongamornlert, Daniel, Lindstrom, Sara, Jugurnauth-Little, Sara, Dadaev, Tokhir, Tymrakiewicz, Malgorzata, Stram, Daniel O., Rand, Kristin, Wan, Peggy, Stram, Alex, Sheng, Xin, Pooler, Loreall C., Park, Karen, Xia, Lucy, Tyrer, Jonathan, Kolonel, Laurence N., Le Marchand, Loic, Hoover, Robert N., Machiela, Mitchell J., Yeager, Merideth, Burdette, Laurie, Chung, Charles C., Hutchinson, Amy, Yu, Kai, Goh, Chee, Ahmed, Mahbubl, Govindasami, Koveela, Guy, Michelle, Tammela, Teuvo L.J., Auvinen, Anssi, Wahlfors, Tiina, Schleutker, Johanna, Visakorpi, Tapio, Leinonen, Katri A., Xu, Jianfeng, Aly, Markus, Donovan, Jenny, Travis, Ruth C., Key, Tim J., Siddiq, Afshan, Canzian, Federico, Khaw, Kay-Tee, Takahashi, Atsushi, Kubo, Michiaki, Pharoah, Paul, Pashayan, Nora, Weischer, Maren, Nordestgaard, Borge G., Nielsen, Sune F., Klarskov, Peter, Røder, Martin Andreas, Iversen, Peter, Thibodeau, Stephen N., McDonnell, Shannon K, Schaid, Daniel J, Stanford, Janet L., Kolb, Suzanne, Holt, Sarah, Knudsen, Beatrice, Coll, Antonio Hurtado, Gapstur, Susan M., Diver, W. Ryan, Stevens, Victoria L., Maier, Christiane, Luedeke, Manuel, Herkommer, Kathleen, Rinckleb, Antje E., Strom, Sara S., Pettaway, Curtis, Yeboah, Edward D., Tettey, Yao, Biritwum, Richard B., Adjei, Andrew A., Tay, Evelyn, Truelove, Ann, Niwa, Shelley, Chokkalingam, Anand P., Cannon-Albright, Lisa, Cybulski, Cezary, Wokołorczyk, Dominika, Kluźniak, Wojciech, Park, Jong, Sellers, Thomas, Lin, Hui-Yi, Isaacs, William B., Partin, Alan W., Brenner, Hermann, Dieffenbach, Aida Karina, Stegmaier, Christa, Chen, Constance, Giovannucci, Edward L., Ma, Jing, Stampfer, Meir, Penney, Kathryn L., Mucci, Lorelei, John, Esther M., Ingles, Sue A., Kittles, Rick A., Murphy, Adam B., Pandha, Hardev, Michael, Agnieszka, Kierzek, Andrzej M., Blot, William, Signorello, Lisa B., Zheng, Wei, Albanes, Demetrius, Virtamo, Jarmo, Weinstein, Stephanie, Nemesure, Barbara, Carpten, John, Leske, Cristina, Wu, Suh-Yuh, Hennis, Anselm, Kibel, Adam S., Rybicki, Benjamin A., Neslund-Dudas, Christine, Hsing, Ann W., Chu, Lisa, Goodman, Phyllis J., Klein, Eric A, Zheng, S. Lilly, Batra, Jyotsna, Clements, Judith, Spurdle, Amanda, Teixeira, Manuel R., Paulo, Paula, Maia, Sofia, Slavov, Chavdar, Kaneva, Radka, Mitev, Vanio, Witte, John S., Casey, Graham, Gillanders, Elizabeth M., Seminara, Daniella, Riboli, Elio, Hamdy, Freddie C., Coetzee, Gerhard A., Li, Qiyuan, Freedman, Matthew L., Hunter, David J., Muir, Kenneth, Gronberg, Henrik, Neal, David E., Southey, Melissa, Giles, Graham G., Severi, Gianluca, Cook, Michael B., Nakagawa, Hidewaki, Wiklund, Fredrik, Kraft, Peter, Chanock, Stephen J., Henderson, Brian E., Easton, Douglas F., Eeles, Rosalind A., and Haiman, Christopher A.

Abstract

Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of >10 million SNPs in 43,303prostate cancer cases and 43,737 controls from studies in populations of European, African, Japanese and Latino ancestry. Twenty-three novel susceptibility loci were revealed at P<5×10-8; 15 variants were identified among men of European ancestry, 7 from multiethnic analyses and one was associated with early-onset prostate cancer. These 23 variants, in combination with the known prostate cancer risk variants, explain 33% of the familial risk of the disease in European ancestry populations. These findings provide new regions for investigation into the pathogenesis of prostate cancer and demonstrate the utility of combining ancestrally diverse populations to discover risk loci for disease.

Published
2014
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30. 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 Saroja, 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 Le, Ambite, José Luis, Buyske, Steven, Florez, Jose C, Crawford, Dana C, Hindorff, Lucia A, Haiman, Christopher A, Peters, Ulrike, and Pankow, James S

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
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32. 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., and Nordestgaard, Børge G.

Subjects
*DISEASE risk factors, *MONOGENIC & polygenic inheritance (Genetics), *PROSTATE cancer patients, *GENEALOGY, *PROSTATE cancer
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 (PRS 269). 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 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 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 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 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 PRS 269 developed from multi-ancestry GWASs and fine-mapping. Our findings suggest that in men of African and European ancestry, genome-wide polygenic risk scores including >1 million variants are not more predictive of prostate cancer risk than a carefully constructed polygenic risk score limited to variants with statistical evidence of an association with prostate cancer risk. [ABSTRACT FROM AUTHOR]

Published
2023
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33. A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

Author

Darst, Burcu F., Hughley, Raymond, Pfennig, Aaron, Hazra, Ujani, Fan, Caoqi, Wan, Peggy, Sheng, Xin, Xia, Lucy, Andrews, Caroline, Chen, Fei, Berndt, Sonja I., Kote-Jarai, Zsofia, Govindasami, Koveela, Bensen, Jeannette T., Ingles, Sue A., Rybicki, Benjamin A., Nemesure, Barbara, John, Esther M., Fowke, Jay H., and Huff, Chad D.

Subjects
*PROSTATE cancer, *PROSTATE cancer patients, *DISEASE risk factors, *GERM cells, *GENEALOGY, *GENE frequency
Abstract

A rare African ancestry–specific germline deletion in HOXB13 (X285K) was associated with an increased risk of overall and advanced prostate cancer and was found only in men of West African ancestry. Men carrying this variant may benefit from earlier prostate cancer screening. A rare African ancestry–specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.40% in Ghana and 0.31% in Nigeria to 0% in Uganda and South Africa, with a range of frequencies in men with admixed African ancestry from North America and Europe (0–0.26%). HOXB13 X285K was associated with 2.4-fold increased odds of prostate cancer (95% confidence interval [CI] = 1.5-3.9, p = 2 × 10−4), with greater risk observed for more aggressive and advanced disease (Gleason ≥8: odds ratio [OR] = 4.7, 95% CI = 2.3–9.5, p = 2 × 10−5; stage T3/T4: OR = 4.5, 95% CI = 2.0–10.0, p = 2 × 10−4; metastatic disease: OR = 5.1, 95% CI = 1.9–13.7, p = 0.001). We estimated that the allele arose in West Africa 1500–4600 yr ago. Further analysis is needed to understand how the HOXB13 X285K variant impacts the HOXB13 protein and function in the prostate. Understanding who carries this mutation may inform prostate cancer screening in men of West African ancestry. A rare African ancestry–specific germline deletion in HOXB13 , found only in men of West African ancestry, was reported to be associated with an increased risk of overall and advanced prostate cancer. Understanding who carries this mutation may help inform screening for prostate cancer in men of West African ancestry. [ABSTRACT FROM AUTHOR]

Published
2022
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34. Hormonal factors and the risk of invasive ovarian cancer: a population-based case-control study

Author

Pike, Malcolm C., Pearce, Celeste L., Peters, Ruth, Cozen, Wendy, Wan, Peggy, and Wu, Anna H.

Subjects
*CANCER invasiveness, *CANCER in women, *OVARIES, *ORAL contraceptives
Abstract

Objective: To examine the influence of hormone-related factors on the risk of invasive epithelial ovarian cancer (ovarian cancer).Design: Population-based case–control study using in-person interviews.Setting: Academic department of preventive medicine.Patient(s): Four hundred seventy-seven ovarian cancer patients and 660 controls.Intervention(s): None.Main outcome measure(s): Numbers of and ages at births, oral contraceptive use, and use of menopausal hormone therapy.Result(s): Compared with nulliparous women, women whose only (last) birth was after age 35 years had an estimated 51% (95% confidence interval: 21%–70%) reduction in risk. If this birth occurred earlier, the reduction in risk was progressively less. Additional (earlier) births reduced the risk further. Oral contraceptive use also reduced risk. Increased body mass index increased risk, but this effect was confined to localized disease and is likely to be a diagnostic bias, as a consequence of other problems associated with being overweight and in itself having no etiological significance.Conclusion(s): If the major protective effect of a late birth can be confirmed, our most challenging task will be to understand the mechanism to develop a chemoprevention approach to exploit this finding. [Copyright &y& Elsevier]

Published
2004
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