Associations between single nucleotide polymorphisms in double-stranded DNA repair pathway genes and familial breast cancer.

Purpose: DNA damage recognition and repair play a major role in risk for breast cancer. We investigated 104 single nucleotide polymorphisms (SNP) in 17 genes whose protein products are involved in double-stranded break repair (DSBR).

Experimental Design: We used a case-control design. Both the case individuals affected with breast cancer or with both breast and ovarian cancers and the controls had similar familial risk of breast cancer and were participants in a high-risk cancer registry.

Results: We found that 12 of the polymorphisms are associated with breast or breast and ovarian cancers, most notably rs16888927, rs16888997, and rs16889040, found in introns of RAD21, suggesting that SNPs in other genes in the DSBR pathway in addition to BRCA1 and BRCA2 may affect breast cancer risk.

Conclusions: SNPs within or near several DSBR DNA repair pathway genes are associated with breast cancer in individuals from a high-risk population. In addition, our study reemphasizes the unique perspective that recruitment of cases and controls from family cancer registries has for gene discovery studies.