Polymorphisms in DNA repair genes and epithelial ovarian cancer risk

• Published in: International journal of cancer Vol. 117; no. 4; pp. 611 - 618
• Main Authors: Auranen, Annika, Song, Honglin, Waterfall, Christy, DiCioccio, Richard A., Kuschel, Bettina, Kjaer, Susanne K., Hogdall, Estrid, Hogdall, Claus, Stratton, John, Whittemore, Alice S., Easton, Douglas F., Ponder, Bruce A.J., Novik, Karen L., Dunning, Alison M., Gayther, Simon, Pharoah, Paul D.P.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 20.11.2005; Wiley-Liss
• Subjects: Adult; Aged; Base Sequence; Biological and medical sciences; Case-Control Studies; DNA Primers; DNA repair; DNA Repair - genetics; Female; Female genital diseases; Genetic Predisposition to Disease; Genotype; Gynecology. Andrology. Obstetrics; Humans; Medical sciences; Middle Aged; Neoplasms, Glandular and Epithelial - genetics; ovarian cancer risk; Ovarian Neoplasms - genetics; Polymorphism, Genetic; polymorphisms; Risk Factors; Tumors; Denmark; United Kingdom; United States; North America; Europe; America; Human; Ovary carcinoma; Genetic variability; Genotype; Malignant tumor; Epidemiology; DNA repair; Female genital diseases; Repair gene; Ovarian diseases; Cancerology; Risk factor; Genetics; Public health; Polymorphism
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.21047

DNA repair gene polymorphisms and mutations are known to influence cancer risk. We studied whether polymorphisms in DNA double strand break (DSB) repair genes are associated with epithelial ovarian cancer (EOC) risk. Up to 1,600 cases and 4,241 controls from 4 separate genetic association studies from 3 countries were genotyped for 13 single nucleotide polymorphisms (SNP) in 6 genes (BRCA1, NBS1, RAD51, RAD52, XRCC2 and XRCC3) involved in homologous recombination of DNA double strand breaks. Genotype specific risks were estimated as odds ratios (OR) by unconditional logistic regression. No association was detected between EOC risk and BRCA1 Q356R, BRCA1 P871L, RAD51 g135c, RAD51 g172t, RAD52 c2259t, NBS1 L34L, NBS1 E185Q, NBS1 A399A, NBS1 P672P, XRCC2 g4324c, XRCC2 c41657t and XRCC3 T241M. The XRCC2 R188H polymorphism was associated with a modest reduction in EOC risk: OR for heterozygotes was 0.8 (95% confidence interval [CI] = 0.7–1.0) and for rare homozygotes 0.3 (0.1–0.9). The XRCC3 a4541g polymorphism, situated in the 5′UTR, and the intronic XRCC3 a17893g polymorphism were not associated with EOC risk in general, but when the serous EOC subset only was analysed, the OR for heterozygotes for a4541g was 1.0 (0.9–1.2) and for the rare homozygotes 0.5 (0.3–0.9). For the XRCC3 a17893g polymorphism, the OR for the heterozygotes and the rare homozygotes were 0.8 (0.7–0.9) and 0.9 (0.7–1.2), respectively. In our study, some polymorphisms in XRCC2 and XRCC3 genes were associated with EOC risk. Further research on the role of these genes on epithelial ovarian cancer is warranted. © 2005 Wiley‐Liss, Inc.