DNA Repair Gene Expression Levels as Indicators of Breast Cancer in the Breast Cancer Family Registry.

ABSTRACT

AIM: The expression level of DNA repair-related genes and their association with breast cancer status among participants of the New York site of the Breast Cancer Family Registry was investigated. MATERIALS AND METHODS: RNA from mononuclear cells in 194 sister sets (n=475 women) were assayed for ATM, BRCA1, MSH2, MUTYH and XPC gene expression levels and analyzed using generalized estimating equations (GEE). RESULTS: Individuals with decreased ATM and MSH2 expression had significantly higher odds for breast cancer compared to individuals with higher levels of expression (odds ratio (OR)=1.1, 95% confidence interval (CI)=1.02, 1.18) and (OR=1.90, 95% CI=1.21, 2.97), respectively. Upon stratifying the GEE model, reductions in ATM and MSH2 expression levels was heightened among women with an extended family history (FH) of breast cancer. CONCLUSION: Reduced expression of ATM and MSH2 compromises DNA repair capacity and, thereby, increases breast cancer prevalence.