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

Abstract

<b>Background:</b> The incidence of esophageal squamous cell cancer (ESCC) is strikingly variable by geographicarea, which reflect different exposures to risk factors, including genetic predisposition. Previous studies ofESCC 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.<br/><b>Methods</b>: Forty-seven ESCC patients from a low-risk area of Southeast China were screened for mutations inthe entire coding region of the BRCA2 gene by direct sequencing. <br/><b>Results</b>: No somatic mutations were observedin tumors. In total, 9 germline missense point mutations, each in one patient, were identified in male sporadicpatients, with a mutation frequency of 19%. Of the 9 mutations, 7 were of heterozygous, while the remaining 2were homozygous. Screening of an additional 94 healthy controls for the 9 mutations identified in ESCC casesshowed that there was only 2 (2%) positive individuals, each carrying one of the mutations. Thus the mutationfrequency 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. <br/><b>Conclusion</b>: This series of cases from a low-riskChinese population presented the highest frequency of germline BRCA2 mutations in ESCC reported to date,highlighting possible etiology roles in this population.