DNA repair and breast carcinoma susceptibility in women

BACKGROUND. Breast carcinoma is the most common cancer and the second leading cause of cancer-related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma. METHODS. A retrospective case-control clinical study was performed to compare age-matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer-free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors. RESULTS. Women with breast carcinoma had a mean DRC of 5.6% +/- 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P < 0.001) in DRC when compared with the control group (DRC = 8.7% +/- 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age-matched controls. Family (odds ratio [OR] = 4.1), maternal lineage (OR = 5.5), and maternal (OR = 12.4) history of breast carcinoma were found to be the only statistically significant (P < 0.05) risk factors associated with the disease. CONCLUSIONS. The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility. (C) 2004 American Cancer Society.