The mutation landscape of multiple cancer predisposition genes in Chinese familial/hereditary breast cancer families.

Objective: Approximately 5%-10% of breast cancer (BC) patients display familial traits that are genetically inherited among the members of a family. The purpose of this study was to profile the germline mutations in 43 genes with different penetration rates and their correlations with phenotypic traits in Chinese familial BC families.

Methods: Ion Torrent S5™-based next generation sequencing was conducted on 116 subjects from 27 Chinese familial BC families.

Results: Eighty-one germline mutations in 27 BC predisposition genes were identified in 82.8% (96/116) of the cases. Among these, 80.8% of the mutated genes were related to DNA damage repair. Fourteen possible disease-causing variants were identified in 13 of 27 BC families. Only 25.9% (7/27) of the BC families exhibited hereditary deficiency in genes, while 22.2% of the BC families exhibited defects in genes. In all, 41.7% (40/96) of the mutation carriers had mutations, 88.5% (85/96) had mutations, and 30.2% (29/96) had both and mutations. The BC patients with mutations had a higher risk of axillary lymph node metastases than those without mutations ( < 0.05). However, the BC patients with mutations frequently had a higher occurrence of benign breast diseases than those without mutations ( < 0.05).

Conclusions: In addition to , genetic variants in DNA repair genes might play significant roles in the development of familial/hereditary BC. Therefore, profiling of multiple BC predisposition genes should be more valuable for screening potential pathogenic germline mutations in Chinese familial/hereditary BC.