Association between invasive ovarian cancer susceptibility and 11 best candidate SNPs from breast cancer genome-wide association study
Year: 2009
Type: article
Study design: Observational Study
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.
Source: Human Molecular Genetics
DOI: 10.1093/hmg/ddp138
Authors: Honglin Song, Susan J. Ramus, Susanne Krüger Kjaer, Richard A. DiCioccio, Georgia Chenevix-Trench, Celeste Leigh Pearce, Estrid Hogdall, Alice S. Whittemore, Valerie McGuire, Claus Hogdall, Jan Blaakaer, Anna H. Wu, David J. Van Den Berg, Daniel O. Stram, Usha Menon, Aleksandra Gentry-Maharaj, Ian J. Jacobs, Penny M. Webb, Jonathan Beesley, Xiaoqing Chen, the Australian Cancer (Ovarian) Study, The Australian Ovarian Cancer Study Group, Mary Anne Rossing, Jennifer A. Doherty, Jenny Chang-Claude, Shan Wang-Gohrke, Marc T. Goodman, Galina Lurie, Pamela J. Thompson, Michael E. Carney, Roberta B. Ness, Kirsten Moysich, Ellen L. Goode, Robert A. Vierkant, Julie M. Cunningham, Stephanie Anderson, Joellen M. Schildkraut, Andrew Berchuck, Edwin S. Iversen, Patricia G. Moorman, Montserrat Garcia-Closas, Stephen Chanock, Jolanta Lissowska, Louise Brinton, Hoda Anton-Culver, Argyrios Ziogas, Wendy R. Brewster, Bruce A.J. Ponder, Douglas F. Easton, Simon A. Gayther, Paul D.P. Pharoah
Institutions: University of Cambridge, University College London, Danish Cancer Society, Roswell Park Comprehensive Cancer Center, QIMR Berghofer Medical Research Institute, University of Southern California, Stanford Medicine, Stanford University, University of Copenhagen, Rigshospitalet, Aarhus University Hospital, Fred Hutch Cancer Center, German Cancer Research Center, Universität Ulm, University of Hawaiʻi at Mānoa, University of Hawaii System, Mayo Clinic, Duke University, Duke Medical Center, Division of Cancer Epidemiology and Genetics, The Maria Sklodowska-Curie National Research Institute of Oncology, University of California, Irvine, University of North Carolina at Chapel Hill
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: green
Funders: U.S. Department of Health and Human Services, Ovarian Cancer Research Fund, Kræftens Bekæmpelse, Wellcome Trust, Lon V. Smith Foundation, Cancer Research UK, National Institute for Health and Care Research, University College London, Bundesministerium für Bildung und Forschung, Max-Planck-Gesellschaft, University College London Hospitals NHS Foundation Trust, Universität Ulm, National Institutes of Health, Medical Research Council, National Health and Medical Research Council, Cancer Council Tasmania, National Cancer Institute, Medical Research and Materiel Command
Awards: G1335914152, G1355612696, Towards cancer control: Population and molecular strategies, G156582752, RISK FACTORS AND PROGNOSTIC FACTORS FOR OVARIAN CANCER, G1675456475, G168441794, G1791794685, G1972180448, Steroid Hormone Genes and Ovarian Cancer Risk, G2342347956, G2590553186, HEREDITARY BREAST CANCER--GENETIC AND MOLECULAR STUDIES, G2833979660, Hereditary Breast Cancer: Genetic and Molecular Studies, G3205575695, SURVEILLANCE EPIDEMIOLOGY AND END RESULTS (SEER), WS No. 12 Patterns of Care DX Year 2008, Collaborative Genetic Study of Ovarian Cancer Risk, G544810358, G5496469482, Epidemiology of Ovarian Cancer:New Hypotheses, G5865683244, G6208597191, G6279653796, G6283257732, G64733685, G667355291, Hormonal Factors in Invasive and LMP Ovarian Cancers, G7009610138, G7367186041, Genetic Variation in the NF-kappaB Pathway and Ovarian Cancer Etiology, G764070827, G8085000608, G827758369, G847461785, G9000001642, G9000182468, Roswell Park Cancer Center Support Grant
OpenAlex ID: W2141070232