Breast cancer (BC) and endometriosis are important reproductive health diseases for women. Although endometriosis is not a malignant condition, some of its characteristics mimic that of a malignancy. Endometriosis is associated with increased risk of certain cancers; however, whether it alters BC risk is unclear. This study evaluates the association of endometriosis and BC and explores whether DNA repair capacity (DRC) plays a role in such a relationship. A case-control study of 991 women (385 with BC and 606 controls, all recruited over 5 years) was undertaken in Puerto Rico. Eighty participants with self-reported surgically diagnosed endometriosis were identified, 20 of whom also had a diagnosis of BC. Data from a structured questionnaire and DRC measurements were assessed to determine the association between BC, DRC, and endometriosis. Participants with BC cases were 50% less likely to have history of endometriosis (OR = 0.5 95%CI: 0.3, 0.9, p = 0.038) than women without BC controls. Findings that did not reach statistical significance included the following: women with history of endometriosis had a slightly higher DRC level than those without it; BC cases and history of endometriosis were less likely to have had endometriosis diagnosis before age 38 as compared to controls with endometriosis. Here we report an inverse association between endometriosis and BC, the former possibly conferring a protective effect on the latter. Although the mechanisms involved are unknown they may include protection provided by higher DRC and or hormonal treatments for endometriosis. A larger sample of endometriosis cases is necessary to confirm these results and answer the question of whether a higher DRC capacity may contribute to this potential protection, and to identify other factors at play.

Previous studies have found a link between a low DNA repair capacity (DRC) level and increased risk for breast cancer (BC). A recent study by Matta et al. 2012 showed that women with BC have an average reduction of 60% in DRC compared to controls (P < 0.001). Using the same group of Hispanic women, we selected a subgroup of cases (n=35) and controls (n=2) who donated their tumors and normal tissue for performing molecular studies in order to 1) compare the expression of DNA repair genes in breast tissue between BC cases and controls without this disease, 2) assess the correlation between gene expression and DRC levels, 3) examine whether DRC levels are associated with tumor DNA repair gene expression profiling when women were stratified according to their hormone receptor status. DRC levels were measured in lymphocytes by means of a host-cell reactivation assay. Gene expression levels were measured in tumors by means of DNA microarray analysis. Twenty-one DNA repair genes were found to be differentially and significantly expressed in women with BC. Those candidate genes were CHEK2, EME1 (MMS4L), ERCC3 (XPB), FANCM, H2AFX (H2AX), HMGB1, HUS1, MBD4, NEIL3, PCNA, RAD1, RAD23B, RAD51, RAD54B, RDM1 (RAD52B), SHFM1 (DSS1), TP1, UBE2N (UBC13) and XRCC5 (Ku80). Most DNA repair genes (n=18 or 82%) were overexpressed, ranging from 3.76-fold (RDM1) to 1.47-fold (XRCC5). Only 4 genes (18%) were underexpressed, ranging from 62% (SAPCD1) to 25% (RAD23B). Statistically significant positive correlations between DRC level and gene expression were found for the RAD51, FANCB and FANCA genes. We discuss the clinical and translational significance of these findings. Our results support the usefulness of studying DNA repair as a measure of BC risk. This study also provides a list of candidate DNA repair genes that might be associated with dysregulation of DNA repair in breast cancer.