Parity Increases the Expression of the NER DNA Repair Pathway in Normal Human Breast Tissue From Premenopausal Women

Women with an early first full-term pregnancy have a reduced lifetime risk of breast cancer as compared to nulliparous women. Microarray analyses of laser-captured epithelium from postmenopausal, parous women identified an increased expression of genes associated with DNA repair (Russo, et al 2006). Therefore, we examined DNA repair (DR) gene expression and sensitivity to death of parous and nulliparous breast tissues in response to radiation. Tissues were obtained from consenting individuals that underwent breast reduction and completed a pre-operative questionnaire containing demographic and cancer risk factor information.  Normal breast tissues were collected, cultured as explants, and were exposed to a low dose of ionizing radiation (γ-IR). The tissues were formalin fixed, paraffin embedded, or frozen for subsequent analysis. We performed quantitative PCR (qPCR) to determine DR gene expression and TUNEL assays to determine levels of cell death in the tissues. Results showed an overall increase in nuclear excision repair (NER) gene expression in parous tissue in response to IR as compared to nulliparous tissue. Our TUNEL data showed decreased apoptosis in +IR parous tissue, suggesting parous tissue may possess an improved DNA repair mechanism that lead to less cell death. This study confirms and extends the data from Russo (2006), suggesting an increased NER pathway gene expression in parous women.  Moreover, parous tissues display an augmented response of NER genes to radiation whereas nulliparous tissue displayed a decreased or no response at all. This study provides evidence that parity status alters the response of breast tissue to DNA damage-induced stresses.