Frequent Germline Mutation in the BRCA2 Gene in Esophageal Squamous Cell Carcinoma Patients from a Low-risk Chinese Population

Background: The incidence of esophageal squamous cell cancer (ESCC) is strikingly variable by geographic area, which reflect different exposures to risk factors, including genetic predisposition. Previous studies of ESCC patients from several high-risk populations suggested that BRCA2 might play a role in the etiology. This study was conducted to screen for mutations of BRCA2 gene in ESCC cases from a low-risk population. Methods: Forty-seven ESCC patients from a low-risk area of Southeast China were screened for mutations in the entire coding region of the BRCA2 gene by direct sequencing. Results: No somatic mutations were observed in tumors. In total, 9 germline missense point mutations, each in one patient, were identified in male sporadic patients, with a mutation frequency of 19%. Of the 9 mutations, 7 were of heterozygous, while the remaining 2 were homozygous. Screening of an additional 94 healthy controls for the 9 mutations identified in ESCC cases showed that there was only 2 (2%) positive individuals, each carrying one of the mutations. Thus the mutation frequency in ESCC cases (19%) was significantly higher than that in healthy controls (OR = 10.9, 95% CI = 2.2-52.8, P = 0.003). No significant associations were observed for germline BRCA2 mutations with age, sex, cigarette smoking, alcohol drinking and family history of cancer. Conclusion: This series of cases from a low-risk Chinese population presented the highest frequency of germline BRCA2 mutations in ESCC reported to date, highlighting possible etiology roles in this population.