p53 expression and risk factors for breast cancer.

摘要

The etiologic heterogeneity of breast cancer was evaluated by examining whether associations between environmental and reproductive risk factors and breast cancer differ according to p53 protein expression status. The relation between the metabolism genes, CYP1A1 and GSTM1, and p53 status were also examined. Data were obtained from the Carolina Breast Cancer Study, a population-based, case-control study of invasive breast cancer conducted among women aged 20–74 in North Carolina. Risk factor profiles for p53+ and p53 − largely overlapped, with the exception of reproductive factors, family history and ionizing radiation exposure. Ever having a first full-term pregnancy was inversely associated with p53− breast cancer (OR: 0.7 (95% CI: 0.7–1.0)) but not associated with p53+ breast cancer. Exposure to ionizing radiation showed a positive association with p53+ breast cancer. The OR for ionizing radiation exposure from chest x-rays and occupational exposure relative to no exposure was higher for p53+ breast cancer (OR: 2.5 (95% CI: 1.1–6.0)) than for p53− breast cancer (OR: 1.2 (95% CI: 0.4–3.3)). Smoking was not associated with p53+ or p53− breast cancer. Incorporating inherited susceptibility factors known to be involved in the metabolism of potential carcinogens in tobacco smoke did not reveal different associations between smoking and breast cancer characterized by p53 status. Polymorphisms in CYP1A1 (m1–m4) and GSTM1 were not associated with p53+ or p53− breast cancer in relation to controls. Joint effects of smoking exposure and genotypes revealed only modest interactions under the additive model, and were not supportive of the original hypotheses. The results of this study provide only minimal evidence of breast cancer heterogeneity as classified by p53 expression status. While preliminary, the results suggest that reproductive variables may contribute to the development of p53− breast cancer through a hormonally-mediated pathway, while radiation exposure may contribute to the development of p53 + breast cancer by adversely affecting the p53 gene.