A prospective study of XRCC1(X-ray cross-complementing group 1) polymorphisms and breast cancer risk

Among the 21,965 women who were cancer-free in 1992 and gave blood between 1998 and 2001, 502 postmenopausal breast cancer cases were diagnosed between 1992 and 2001; 502 controls were matched to cases on age, race/ethnicity, and date of blood collection. Genotyping on DNA extracted from buffy coat was performed with Taqman. Conditional logistic regression was used to examine the association between each polymorphism and breast cancer risk controlling for breast cancer risk factors. We also examined whether factors associated with DNA damage, such as smoking and antioxidant intake, modified the association between XRCC1 polymorphisms and breast cancer.

We observed a significant inverse association between Trp194 carriers (Trp/Trp and Trp/Arg) compared with Trp194 non-carriers in relation to breast cancer (Arg/Arg) (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95). The inverse association between breast cancer and Trp194 carriers compared with non-carriers was slightly stronger among smokers (OR 0.47, 95% CI 0.24 to 0.94) than never smokers (OR 0.78, 95% CI 0.43 to 1.40). An increased risk associated with the Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was observed only among women who reported ever smoking cigarettes (OR 2.76, 95% CI 1.36 to 5.63), and not in women who were lifelong non-smokers (OR 0.64, 95% CI 0.33 to 1.26). No other factor examined modified the association between XRCC1 polymorphisms and breast cancer risk.