BMC Cancer 2004, 4 http://www.biomedcentral.com/1471-2407/4/9 decreased breast cancer risk observed for APEX D148E heterozygotes. It is possible that one or more of the XRCC1 R194W, XRCC1 R399Q, BRIP1 P919S variants could eventually be regarded as low-penetrance risk alle- les for breast cancer, but after adjustment for multiple comparisons, none remained statistically significant. Ulti- mately, results from this kin-cohort analysis can be com- bined with findings from the standard case-control study for a more consistent interpretation of the risk associated with common genetic variants. Conclusions Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles. Previous association studies of increased breast cancer risk for BRCA2 N372H and decreased function for APEX D148E variants were not in agreement with our findings of decreased risks. 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