The Analysis Of BRCA1/2 Mutations Among Familial And/or Early-onset Breast Cancer Patients In Eastern Shandong Of China

Objective Breast cancer is one of the most common malignancy among women. BRCA1 (breast cancer gene 1, early-onset) and BRCA2 (breast cancer gene 2, early-onset) is the tumor suppressor genes that most closely related to breast cancer. Carrying the mutant gene women suffer a significant increase in risk of breast cancer and ovarian cancer, while the age of onset in advance. At present foreign other groups have conducted extensive research and found some founder mutations, which benifit in early census and early preventive intervention. Most of domestic study were based on small sample or part of the gene, lack systemic report of large-scale Chinese population. Based on this study of 52 cases of familial and early-onset breast cancer cases in estern Shandong of China for BRCA1/2 gene screening, we may have a better understanding of BRCA1/2 gene mutation in this region.Methods: Fifty-two familial and/or early-onset breast cancer patients from unrelated families were analyzed. Genomic DNA was collected from the peripheral blood mononuclear cells using PureGene DNA purification system. Thirty-six pairs and 42 pairs of primers were designed for the PCR amplications on the the coding sequences and exon-intron boundaries of BRCA1 and BRCA2 gene. Amplified PCR products were analyzed by denaturing high performance liquid chromatography (DHPLC). And the abnormal fragments were confirmed with direct DNA sequencing.Results: three kinds of disease-related mutations of the BRCA1 gene(2229 delAA, 2257C> G, 3413delT) were found in four unrelated families, the mutation rate is 7.7% (4 / 52), the mutation rate was 12% (3 / 25) in familial breast cancer patients, and 18.8% (3 /16) in the patients with first-degree affected relative .Another case of disease-related mutation occurred in a 34-year-old breast cancer patient, the mutation does not exit in the BIC database and had not been reported in the literature. In early-onset breast cancer patient, the mutation rate was 3.7% (1 / 27). Meanwhile,three kinds of disease-related mutations of the BRCA2 gene (2001delTTAT,4099 C>T, 5873C>A)were found in 3 unrelated families, the mutation rate is 5.8% (3/52) .In 25 patients with familial breast cancer, the mutation rate was 12% (3 / 25), no pathogenic BRCA2 mutation was found in 27 cases of simple early-onset breast cancer.Conclusions: BRCA1 and BRCA2 mutations may play an important role in the familial breast cance in eastern Shandong of China r, but not in the early-onset breast cancer. It is necessary to give genetic test for familial breast cancer patients in this population, especially those population at high familial risk of breast cancer.