Frequency of BRCA1 and BRCA2 Mutations in Individuals with Breast and Ovarian Cancer in a Chinese Hakka Population Using Next-Generation Sequencing.

Background: It is necessary to investigate the frequency of BRCA1 and BRCA2 mutations in Hakka populations due to the variations in breast cancer epidemiology and genetics.

Methods: 359 breast cancer patients and 66 ovarian cancer patients were included in this retrospective clinical study. Mutations of BRCA1 and BRCA2 were detected in blood samples by semiconductor sequencing.

Results: The sensitivity of tumor markers including CEA, CA15-3, CA12-5, and CA199 for screening breast cancer was 16.44, 15.11, 8.44, and 7.56%, the combination of these 4 tumor markers reached the highest sensitivity index (31.11%). For ovarian cancer, the tumor markers were CA12-5 (54.05%), HE-4 (54.05%), CA72-4 (51.35%), and CEA (2.70%) in order of decreasing sensitivity. Moreover, the combination of these 4 tumor markers has the best sensitivity (75.68%) for screening ovarian cancer. In breast cancer patients, we found 5 (1.39%) patients with mutations in BRCA1, 13 (3.62%) mutations in BRCA2, and the total carrier rate is 5.01% (18/359). For ovarian cancer patients, the corresponding results were 3 (4.54%) mutations, 2 (3.03%) mutations, and 7.58% (5/66), respectively. The proportion of BRCA mutations was 5.41% (23/425) in breast and ovarian cancer patients of a Hakka population. The pathogenic, likely pathogenic, and benign mutations, and mutations of uncertain significance in this study mainly occurred in exon 14 of the BRCA1 gene, and exon 10 and exon 11 of the BRCA2 gene.

Conclusions: Understanding the spectrum and frequency of BRCA1 and BRCA2 mutations in a Hakka population will assist in the prevention and control of hereditary breast and ovarian cancers in this population.