PDF(Pubmed)
Abstract：
Among neoplastic diseases, breast cancer (BC) is one of the most influenced by gender. Despite common misconceptions associating BC as a women-only disease, BC can also occur in men. Additionally, transgender individuals may also experience BC. Genetic risk factors play a relevant role in BC predisposition, with important implications in precision prevention and treatment. The genetic architecture of BC susceptibility is similar in women and men, with high-, moderate-, and low-penetrance risk variants; however, some sex-specific features have emerged. Inherited high-penetrance pathogenic variants (PVs) in BRCA1 and BRCA2 genes are the strongest BC genetic risk factor. BRCA1 and BRCA2 PVs are more commonly associated with increased risk of female and male BC, respectively. Notably, BRCA-associated BCs are characterized by sex-specific pathologic features. Recently, next-generation sequencing technologies have helped to provide more insights on the role of moderate-penetrance BC risk variants, particularly in PALB2, CHEK2, and ATM genes, while international collaborative genome-wide association studies have contributed evidence on common low-penetrance BC risk variants, on their combined effect in polygenic models, and on their role as risk modulators in BRCA1/2 PV carriers. Overall, all these studies suggested that the genetic basis of male BC, although similar, may differ from female BC. Evaluating the genetic component of male BC as a distinct entity from female BC is the first step to improve both personalized risk assessment and therapeutic choices of patients of both sexes in order to reach gender equality in BC care. In this review, we summarize the latest research in the field of BC genetic predisposition with a particular focus on similarities and differences in male and female BC, and we also discuss the implications, challenges, and open issues that surround the establishment of a gender-oriented clinical management for BC.
摘要：
在肿瘤性疾病中，乳腺癌（BC）是受性别影响最大的癌症之一。尽管常见的误解将BC视为女性疾病，BC也可发生在男性身上。此外,变性人也可能经历BC。遗传风险因素在BC易感性中起相关作用，对精准预防和治疗具有重要意义。女性和男性的BC易感性遗传结构相似，与高,moderate-,和低外显率风险变体；然而，一些特定性别的特征已经出现。BRCA1和BRCA2基因中遗传的高外显率致病变异体(PVs)是最强的BC遗传风险因子。BRCA1和BRCA2PV通常与女性和男性BC的风险增加有关，分别。值得注意的是,BRCA相关的BCs以性别特异性病理特征为特征。最近,下一代测序技术有助于提供更多关于中度外显率BC风险变异的作用的见解，特别是在PALB2，CHEK2和ATM基因中，虽然国际合作的全基因组关联研究提供了常见的低外显率BC风险变异的证据，在多基因模型中，以及它们在BRCA1/2光伏运营商中作为风险调节剂的作用。总的来说,所有这些研究表明，男性BC的遗传基础，虽然相似,可能与女性BC不同。将男性BC的遗传成分评估为与女性BC不同的实体是改善两种性别患者的个性化风险评估和治疗选择的第一步，以实现BC护理中的性别平等。在这次审查中,我们总结了BC遗传易感性领域的最新研究，特别关注男性和女性BC的异同，我们还讨论了其中的含义，挑战,以及围绕建立以性别为导向的BC临床管理的开放问题。
