Despite their ubiquitous expression, the inheritance of monoallelic germline mutations in breast cancer susceptibility gene type 1 or 2 (BRCA1/2) poses tissue-specific variations in cancer risks and primarily associate with familial breast and ovarian cancers. The molecular basis of this tissue-specific tumor incidence remains unknown and intriguing to cancer researchers. A plethora of recent reports support the idea that several nongenetic factors present in the tissue microenvironment could induce tumors in the mutant BRCA1/2 background. This Opinion article summarizes the recent advances on tissue-specific carcinogens and their complex crosstalk with the compromised DNA repair machinery of BRCA1/2-mutant cells. Finally, we present our perspective on the therapeutic and chemopreventive interpretations of these developments.

尽管它们无处不在的表达，单等位基因种系突变的遗传在乳腺癌易感基因类型1或2（BRCA1 / 2）在癌症风险中造成组织特异性变异，并且主要与家族性乳腺癌和卵巢癌有关。这种组织特异性肿瘤发生率的分子基础仍然未知，并且对癌症研究人员很感兴趣。大量最新报告支持这样的想法，即存在于组织微环境中的几种非遗传因素可在突变的BRCA1 / 2背景中诱导肿瘤。该意见文章总结了特定组织致癌物及其与BRCA1 / 2突变细胞受损的DNA修复机制的复杂串扰的最新进展。最后，我们对这些发展的治疗和化学预防解释提出了自己的观点。