Polymorphisms in the DNA repair gene XRCC1 and breast cancer

X-ray repair cross complementing group 1 (XRCC1) encodes a protein involved in base excision repair. We examined the association of polymorphisms in X RCC1 (codon 194 Arg --> Trp and codon 399 Arg --> Gln) and breast cancer in the Carolina Breast Cancer Study, a population-based case-control study in North Carolina. No association was observed between XRCC1 codon 194 genoty pe and breast cancer, and odds ratios (ORs) were not modified by smoking or radiation exposure. A positive association for XRCC1 codon 399 Arg/Gln or Gln/Gln genotypes compared with Arg/Arg was found among African Americans ( 253 cases, 266 controls; OR = 1,7, 95% confidence interval, 1,1-2,4) but no t whites (386 cases, 381 controls; OR = 1,0, 95% confidence interval, 0,8-1 ,4), Among African-American women, ORs for the duration of smoking were ele vated among women with XRCC1 codon 399 Arg/Arg genotype (trend test; P < 0. 001) but not Arg/Gln or Gln/Gln (P = 0,23), There was no difference in OR f or smoking according to XRCC1 codon 399 genotype in white women. ORs for oc cupational exposure to ionizing radiation were stronger for African-America n and white women with codon 399 Arg/Arg genotype, High-dose radiation to t he chest was more strongly associated with breast cancer among white women with XRCC1 codon 399 Arg/Arg genotype, Our results suggest that XRRC1 codon 399 genotype may influence breast cancer risk, perhaps by modifying the ef fects of environmental exposures. However, interpretation of our results is Limited by incomplete knowledge regarding the biological function of XRCC1 alleles.