title: The functional BRCA1 rs799917 genetic polymorphism is associated with gastric cancer risk in a Chinese Han population.
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.
authors.affiliation: Department of Vascular Surgery, QianFoShan Hospital, Shandong University, Jinan, Shandong Province, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Longfang
authors.initials: L
authors.lastname: Xu
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.forename: Kesen
authors.initials: K
authors.lastname: Xu
authors.forename: Guixia
authors.initials: G
authors.lastname: Li
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human