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7 results on '"The Ovarian Cancer Association Consortium (OCAC)"'

1. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Author

Zhang, Yan Dora, Hurson, Amber N, Zhang, Haoyu, Choudhury, Parichoy Pal, Easton, Douglas F, Milne, Roger L, Simard, Jacques, Hall, Per, Michailidou, Kyriaki, Dennis, Joe, Schmidt, Marjanka K, Chang-Claude, Jenny, Gharahkhani, Puya, Whiteman, David, Campbell, Peter T, Hoffmeister, Michael, Jenkins, Mark, Peters, Ulrike, Hsu, Li, Gruber, Stephen B, Casey, Graham, Schmit, Stephanie L, O'Mara, Tracy A, Spurdle, Amanda B, Thompson, Deborah J, Tomlinson, Ian, De Vivo, Immaculata, Landi, Maria Teresa, Law, Matthew H, Iles, Mark M, Demenais, Florence, Kumar, Rajiv, MacGregor, Stuart, Bishop, D Timothy, Ward, Sarah V, Bondy, Melissa L, Houlston, Richard, Wiencke, John K, Melin, Beatrice, Barnholtz-Sloan, Jill, Kinnersley, Ben, Wrensch, Margaret R, Amos, Christopher I, Hung, Rayjean J, Brennan, Paul, McKay, James, Caporaso, Neil E, Berndt, Sonja I, Birmann, Brenda M, Camp, Nicola J, Kraft, Peter, Rothman, Nathaniel, Slager, Susan L, Berchuck, Andrew, Pharoah, Paul DP, Sellers, Thomas A, Gayther, Simon A, Pearce, Celeste L, Goode, Ellen L, Schildkraut, Joellen M, Moysich, Kirsten B, Amundadottir, Laufey T, Jacobs, Eric J, Klein, Alison P, Petersen, Gloria M, Risch, Harvey A, Stolzenberg-Solomon, Rachel Z, Wolpin, Brian M, Li, Donghui, Eeles, Rosalind A, Haiman, Christopher A, Kote-Jarai, Zsofia, Schumacher, Fredrick R, Al Olama, Ali Amin, Purdue, Mark P, Scelo, Ghislaine, Dalgaard, Marlene D, Greene, Mark H, Grotmol, Tom, Kanetsky, Peter A, McGlynn, Katherine A, Nathanson, Katherine L, Turnbull, Clare, Wiklund, Fredrik, Breast Cancer Association Consortium (BCAC), Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL)

Subjects
Breast Cancer Association Consortium, Barrett’s and Esophageal Adenocarcinoma Consortium, Colon Cancer Family Registry, Transdisciplinary Studies of Genetic Variation in Colorectal Cancer, Endometrial Cancer Association Consortium, Genetics and Epidemiology of Colorectal Cancer Consortium, Melanoma Genetics Consortium, Glioma International Case-Control Study, International Lung Cancer Consortium, Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies, Ovarian Cancer Association Consortium, Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium, Pancreatic Cancer Cohort Consortium, Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome, Renal Cancer GWAS, Testicular Cancer Consortium, Animals, Humans, Neoplasms, Genetic Predisposition to Disease, Incidence, Risk Assessment, Risk Factors, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Models, Genetic, Female, Male, Genome-Wide Association Study, Human Genome, Prevention, Cancer, Prostate Cancer, Genetics, Urologic Diseases, 2.1 Biological and endogenous factors
Abstract

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

Published
2020

2. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

Author

Yan Dora Zhang, Amber N. Hurson, Haoyu Zhang, Parichoy Pal Choudhury, Douglas F. Easton, Roger L. Milne, Jacques Simard, Per Hall, Kyriaki Michailidou, Joe Dennis, Marjanka K. Schmidt, Jenny Chang-Claude, Puya Gharahkhani, David Whiteman, Peter T. Campbell, Michael Hoffmeister, Mark Jenkins, Ulrike Peters, Li Hsu, Stephen B. Gruber, Graham Casey, Stephanie L. Schmit, Tracy A. O’Mara, Amanda B. Spurdle, Deborah J. Thompson, Ian Tomlinson, Immaculata De Vivo, Maria Teresa Landi, Matthew H. Law, Mark M. Iles, Florence Demenais, Rajiv Kumar, Stuart MacGregor, D. Timothy Bishop, Sarah V. Ward, Melissa L. Bondy, Richard Houlston, John K. Wiencke, Beatrice Melin, Jill Barnholtz-Sloan, Ben Kinnersley, Margaret R. Wrensch, Christopher I. Amos, Rayjean J. Hung, Paul Brennan, James McKay, Neil E. Caporaso, Sonja I. Berndt, Brenda M. Birmann, Nicola J. Camp, Peter Kraft, Nathaniel Rothman, Susan L. Slager, Andrew Berchuck, Paul D. P. Pharoah, Thomas A. Sellers, Simon A. Gayther, Celeste L. Pearce, Ellen L. Goode, Joellen M. Schildkraut, Kirsten B. Moysich, Laufey T. Amundadottir, Eric J. Jacobs, Alison P. Klein, Gloria M. Petersen, Harvey A. Risch, Rachel Z. Stolzenberg-Solomon, Brian M. Wolpin, Donghui Li, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote-Jarai, Fredrick R. Schumacher, Ali Amin Al Olama, Mark P. Purdue, Ghislaine Scelo, Marlene D. Dalgaard, Mark H. Greene, Tom Grotmol, Peter A. Kanetsky, Katherine A. McGlynn, Katherine L. Nathanson, Clare Turnbull, Fredrik Wiklund, Breast Cancer Association Consortium (BCAC), Barrett’s and Esophageal Adenocarcinoma Consortium (BEACON), Colon Cancer Family Registry (CCFR), Transdisciplinary Studies of Genetic Variation in Colorectal Cancer (CORECT), Endometrial Cancer Association Consortium (ECAC), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), Melanoma Genetics Consortium (GenoMEL), Glioma International Case-Control Study (GICC), International Lung Cancer Consortium (ILCCO), Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium, International Consortium of Investigators Working on Non-Hodgkin’s Lymphoma Epidemiologic Studies (InterLymph), Ovarian Cancer Association Consortium (OCAC), Oral Cancer GWAS, Pancreatic Cancer Case-Control Consortium (PanC4), Pancreatic Cancer Cohort Consortium (PanScan), Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL), Renal Cancer GWAS, Testicular Cancer Consortium (TECAC), Stephen J. Chanock, Nilanjan Chatterjee, and Montserrat Garcia-Closas

Subjects
Science
Abstract

In cancer many gene variants may contribute to disease etiology, but the impact of a given gene variant may have varied effect size. Here, the authors analyse summary statistics of genome-wide association studies from fourteen cancers, and show the utility of polygenic risk scores may vary depending on cancer type.

Published
2020
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3. Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions

Author

Data gedreven innovatie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epi Team 3, Dareng, Eileen O., Coetzee, Simon G., Tyrer, Jonathan P., Peng, Pei Chen, Rosenow, Will, Chen, Stephanie, Davis, Brian D., Dezem, Felipe Segato, Seo, Ji Heui, Nameki, Robbin, Reyes, Alberto L., Aben, Katja K.H., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Bandera, Elisa V., Beane Freeman, Laura E., Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bolton, Kelly L., Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Cai, Hui, Campbell, Ian, Cannioto, Rikki, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chenevix-Trench, Georgia, Chiew, Yoke Eng, Cook, Linda S., DeFazio, Anna, Dennis, Joe, Doherty, Jennifer A., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Ene, Gabrielle, Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Fostira, Florentia, Onland-Moret, N. Charlotte, AOCS Group, OPAL Study Group, The Ovarian Cancer Association Consortium (OCAC), Data gedreven innovatie, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Circulatory Health, Cardiovasculaire Epi Team 3, Dareng, Eileen O., Coetzee, Simon G., Tyrer, Jonathan P., Peng, Pei Chen, Rosenow, Will, Chen, Stephanie, Davis, Brian D., Dezem, Felipe Segato, Seo, Ji Heui, Nameki, Robbin, Reyes, Alberto L., Aben, Katja K.H., Anton-Culver, Hoda, Antonenkova, Natalia N., Aravantinos, Gerasimos, Bandera, Elisa V., Beane Freeman, Laura E., Beckmann, Matthias W., Beeghly-Fadiel, Alicia, Benitez, Javier, Bernardini, Marcus Q., Bjorge, Line, Black, Amanda, Bogdanova, Natalia V., Bolton, Kelly L., Brenton, James D., Budzilowska, Agnieszka, Butzow, Ralf, Cai, Hui, Campbell, Ian, Cannioto, Rikki, Chang-Claude, Jenny, Chanock, Stephen J., Chen, Kexin, Chenevix-Trench, Georgia, Chiew, Yoke Eng, Cook, Linda S., DeFazio, Anna, Dennis, Joe, Doherty, Jennifer A., Dörk, Thilo, du Bois, Andreas, Dürst, Matthias, Eccles, Diana M., Ene, Gabrielle, Fasching, Peter A., Flanagan, James M., Fortner, Renée T., Fostira, Florentia, Onland-Moret, N. Charlotte, AOCS Group, OPAL Study Group, and The Ovarian Cancer Association Consortium (OCAC)

Published
2024

4. Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study.

Author

Song, Honglin, Ramus, Susan J, Kjaer, Susanne Krüger, DiCioccio, Richard A, Chenevix-Trench, Georgia, Pearce, Celeste Leigh, Hogdall, Estrid, Whittemore, Alice S, McGuire, Valerie, Hogdall, Claus, Blaakaer, Jan, Wu, Anna H, Van Den Berg, David J, Stram, Daniel O, Menon, Usha, Gentry-Maharaj, Aleksandra, Jacobs, Ian J, Webb, Penny M, Beesley, Jonathan, Chen, Xiaoqing, Australian Cancer (Ovarian) Study, Australian Ovarian Cancer Study Group, Rossing, Mary Anne, Doherty, Jennifer A, Chang-Claude, Jenny, Wang-Gohrke, Shan, Goodman, Marc T, Lurie, Galina, Thompson, Pamela J, Carney, Michael E, Ness, Roberta B, Moysich, Kirsten, Goode, Ellen L, Vierkant, Robert A, Cunningham, Julie M, Anderson, Stephanie, Schildkraut, Joellen M, Berchuck, Andrew, Iversen, Edwin S, Moorman, Patricia G, Garcia-Closas, Montserrat, Chanock, Stephen, Lissowska, Jolanta, Brinton, Louise, Anton-Culver, Hoda, Ziogas, Argyrios, Brewster, Wendy R, Ponder, Bruce AJ, Easton, Douglas F, Gayther, Simon A, Pharoah, Paul DP, and Ovarian Cancer Association Consortium (OCAC)

Subjects
Australian Cancer (Ovarian) Study, Australian Ovarian Cancer Study Group, Ovarian Cancer Association Consortium, Humans, Breast Neoplasms, Ovarian Neoplasms, Genetic Predisposition to Disease, Glycoproteins, Neuropeptides, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, European Continental Ancestry Group, Female, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Clinical Research, Breast Cancer, Aging, Cancer, Rare Diseases, Prevention, Human Genome, Genetics, Ovarian Cancer, 2.1 Biological and endogenous factors, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend < 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function.

Published
2009

5. Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals

Author

Chen, H, Majumdar, A, Wang, L, Kar, S, Brown, KM, Feng, H, Turman, C, Dennis, J, Easton, D, Michailidou, K, Simard, J, Breast Cancer Association Consortium (BCAC), Bishop, T, Cheng, IC, Huyghe, JR, Schmit, SL, Colorectal Transdisciplinary Study (CORECT), Colon Cancer Family Registry Study (CCFR), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO, O'Mara, TA, Spurdle, AB, Endometrial Cancer Association Consortium (ECAC), Gharahkhani, P, Schumacher, J, Jankowski, J, Gockel, I, Esophageal Cancer GWAS Consortium, Bondy, ML, Houlston, RS, Jenkins, RB, Melin, B, Glioma International Case Control Consortium (GICC), Lesseur, C, Ness, AR, Diergaarde, B, Olshan, AF, Head-Neck Cancer GWAS Consortium, Amos, CI, Christiani, DC, Landi, MT, McKay, JD, International Lung Cancer Consortium (ILCCO), Brossard, M, Iles, MM, Law, MH, MacGregor, S, Melanoma GWAS Consortium, Beesley, J, Jones, MR, Tyrer, J, Winham, SJ, Ovarian Cancer Association Consortium (OCAC), Klein, AP, Petersen, G, Li, D, Wolpin, BM, Pancreatic Cancer Case-Control Consortium (PANC4), Pancreatic Cancer Cohort Consortium (PanScan), Eeles, RA, Haiman, CA, Kote-Jarai, Z, Schumacher, FR, PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS, Brennan, P, Chanock, SJ, Gaborieau, V, Purdue, MP, Renal Cancer GWAS Consortium, Pharoah, P, Hung, RJ, Amundadottir, LT, Kraft, P, Pasaniuc, B, and Lindström, S

Abstract

Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.

Published
2021

6. Identification of novel epithelial ovarian cancer loci in women of African ancestry

Author

Manichaikul, Ani, Peres, Lauren C, Wang, Xin-Qun, Barnard, Mollie E, Chyn, Deanna, Sheng, Xin, Du, Zhaohui, Tyrer, Jonathan, Dennis, Joseph, Schwartz, Ann G, Cote, Michele L, Peters, Edward, Moorman, Patricia G, Bondy, Melissa, Barnholtz-Sloan, Jill S, Terry, Paul, Alberg, Anthony J, Bandera, Elisa V, Funkhouser, Ellen, Wu, Anna H, Pearce, Celeste Leigh, Pike, Malcom, Setiawan, Veronica Wendy, Haiman, Christopher A, African American Breast Cancer Consortium (AABC), African Ancestry Prostate Cancer Consortium (AAPC), Palmer, Julie R, LeMarchand, Loic, Wilkens, Lynne R, Berchuck, Andrew, Doherty, Jennifer A, Modugno, Francesmary, Ness, Roberta, Moysich, Kirsten, Karlan, Beth Y, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Lawrenson, Kate, Gayther, Simon, Sellers, Thomas A, Pharoah, Paul, Schildkraut, Joellen M, African American Cancer Epidemiology Study (AACES) and the Ovarian Cancer Association Consortium (OCAC), Peres, Lauren C [0000-0002-6620-8600], Du, Zhaohui [0000-0002-7125-8928], Barnholtz-Sloan, Jill S [0000-0001-6190-9304], Pearce, Celeste Leigh [0000-0002-8023-7846], Pike, Malcom [0000-0003-4891-1199], Modugno, Francesmary [0000-0003-0637-1534], Lawrenson, Kate [0000-0002-6469-2515], Schildkraut, Joellen M [0000-0002-0990-9339], and Apollo - University of Cambridge Repository

Subjects
Follistatin, endocrine system diseases, Oncology and Carcinogenesis, Black People, Breast Neoplasms, Carcinoma, Ovarian Epithelial, Polymorphism, Single Nucleotide, African Ancestry Prostate Cancer Consortium, White People, Rare Diseases, Antigens, Neoplasm, Clinical Research, Ovarian Epithelial, Genetics, Humans, 2.1 Biological and endogenous factors, Genetic Predisposition to Disease, Oncology & Carcinogenesis, Antigens, Polymorphism, Aetiology, genome wide association study, Cancer, eQTLs, Prevention, Carcinoma, Aldo-Keto Reductase Family 1 Member C3, African American Cancer Epidemiology Study (AACES) and the Ovarian Cancer Association Consortium, African American Breast Cancer Consortium, Single Nucleotide, United States, Neoplasm Proteins, Ovarian Cancer, Black or African American, ovarian cancer, African ancestry, gene expression, Neoplasm, Female, Genome-Wide Association Study, Biotechnology
Abstract

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p

Published
2020

7. Identification of novel epithelial ovarian cancer loci in women of African ancestry

Author

Manichaikul, Ani, Peres, Lauren C, Wang, Xin-Qun, Barnard, Mollie E, Chyn, Deanna, Sheng, Xin, Du, Zhaohui, Tyrer, Jonathan, Dennis, Joseph, Schwartz, Ann G, Cote, Michele L, Peters, Edward, Moorman, Patricia G, Bondy, Melissa, Barnholtz-Sloan, Jill S, Terry, Paul, Alberg, Anthony J, Bandera, Elisa V, Funkhouser, Ellen, Wu, Anna H, Pearce, Celeste Leigh, Pike, Malcom, Setiawan, Veronica Wendy, Haiman, Christopher A, African American Breast Cancer Consortium (AABC), African Ancestry Prostate Cancer Consortium (AAPC), Palmer, Julie R, LeMarchand, Loic, Wilkens, Lynne R, Berchuck, Andrew, Doherty, Jennifer A, Modugno, Francesmary, Ness, Roberta, Moysich, Kirsten, Karlan, Beth Y, Whittemore, Alice S, McGuire, Valerie, Sieh, Weiva, Lawrenson, Kate, Gayther, Simon, Sellers, Thomas A, Pharoah, Paul, Schildkraut, Joellen M, and African American Cancer Epidemiology Study (AACES) And The Ovarian Cancer Association Consortium (OCAC)

Subjects
Follistatin, endocrine system diseases, eQTLs, Aldo-Keto Reductase Family 1 Member C3, Black People, Breast Neoplasms, Carcinoma, Ovarian Epithelial, Polymorphism, Single Nucleotide, female genital diseases and pregnancy complications, United States, White People, 3. Good health, Neoplasm Proteins, Black or African American, ovarian cancer, African ancestry, Antigens, Neoplasm, gene expression, Humans, Female, Genetic Predisposition to Disease, genome wide association study, Genome-Wide Association Study
Abstract

Women of African ancestry have lower incidence of epithelial ovarian cancer (EOC) yet worse survival compared to women of European ancestry. We conducted a genome-wide association study in African ancestry women with 755 EOC cases, including 537 high-grade serous ovarian carcinomas (HGSOC) and 1,235 controls. We identified four novel loci with suggestive evidence of association with EOC (p < 1 × 10-6 ), including rs4525119 (intronic to AKR1C3), rs7643459 (intronic to LOC101927394), rs4286604 (12 kb 3' of UGT2A2) and rs142091544 (5 kb 5' of WWC1). For HGSOC, we identified six loci with suggestive evidence of association including rs37792 (132 kb 5' of follistatin [FST]), rs57403204 (81 kb 3' of MAGEC1), rs79079890 (LOC105376360 intronic), rs66459581 (5 kb 5' of PRPSAP1), rs116046250 (GABRG3 intronic) and rs192876988 (32 kb 3' of GK2). Among the identified variants, two are near genes known to regulate hormones and diseases of the ovary (AKR1C3 and FST), and two are linked to cancer (AKR1C3 and MAGEC1). In follow-up studies of the 10 identified variants, the GK2 region SNP, rs192876988, showed an inverse association with EOC in European ancestry women (p = 0.002), increased risk of ER positive breast cancer in African ancestry women (p = 0.027) and decreased expression of GK2 in HGSOC tissue from African ancestry women (p = 0.004). A European ancestry-derived polygenic risk score showed positive associations with EOC and HGSOC in women of African ancestry suggesting shared genetic architecture. Our investigation presents evidence of variants for EOC shared among European and African ancestry women and identifies novel EOC risk loci in women of African ancestry.

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