乳腺癌易感基因突变的狭窄分布及其人群差异性

最近10多年来,包括最重要的BRCA1/2在内的多种女性乳腺癌发生发展相关易感基因获得鉴定,并依据其肿瘤风险相关性程度被分别归入高、中和低外显率组别.随后它们的遗传学变异及致病机制研究在世界范围内得以广泛深入地开展,并揭示出其胚系突变具有人群或地域差异性,且局限于仅占10%~20%家族遗传性和早发性乳腺癌的狭窄分布概貌.这些结果转而提示对于大量散发性乳腺癌发病分子机制的研究而言,必须更深入地探讨多重低风险易感多态性复合效应的影响.

Limited Distribution of Human Breast Cancer Susceptibility Gene Mutation and its Populational Heterogeneity

In recent 10 years,many kinds of susceptibility genes to human breast cancer genesis and devel-opment—including the most important ones,BRCA1/2,have been identified and classified into high-,moder-ate-,and low-penetrance groups according to their risk degree relatively to the cancer.The subsequent ex-ploration of their genetic changes and mechanisms performed worldwide has disclosed a profile of their pop-ulationally or regionally heterogeneous germline mutations with a limited occupation in familial and young breast cancers which are of only 10%~20% of the cases.Such results in turn indicate the necessity of dis-cussing multiple low-risk genetic polymorphisms with their composite effects contributing to the molecular mechanism for those vast sporadic breast cancers.