| Literature DB >> 19304784 |
Honglin Song1, 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, 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.
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.Entities:
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Year: 2009 PMID： 19304784 PMCID： PMC2685754 DOI： 10.1093/hmg/ddp138
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150