Abstract
BRCA1 is a crucial tumor suppressor which plays an essential role in maintaining genomic stability and integrity. Accumulated evidences demonstrated that there is frequent chromosome loss of BRCA1 or significant BRCA1 down-regulation via hypermethylation of its promoter in human gastric cancer specimens, highlighting the tumor-suppressing function of BRCA1 in gastric carcinogenesis. There is an rs799917 T>C single nucleotide polymorphism (SNP) located in the BRCA1 coding sequence (CDS). This SNP can disturb the interaction between BRCA1 mRNA and miR-638 and result in significantly decreased BRCA1 expression among carriers of rs799917C allele. In this study, we investigated the association between rs799917 and gastric cancer risk in a Chinese Han population using a case-control design. A total of 660 gastric cancer patients and 800 controls were enrolled and genotyped. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by logistic regression. We found that individuals with the rs799917 CT genotype was significantly associated with gastric cancer risk (OR = 1.81, 95% CI = 1.28-2.56; P = 0.001). Individuals having the rs799917 CC genotype had an OR of 1.40 (95% CI = 1.17-1.68; P = 2.2 × 10(-4)) for developing gastric cancer, compared with individual having the rs799917 TT genotype. However, stratified analyses did not find any evident gene-covariates interaction. Our results for the first time indicate that the functional BRCA1 rs799917 polymorphism contributes to gastric cancer susceptibility.
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More From: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine
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