The purpose of this study was to identify functional genetic variants in the promoter of
tumor necrosis factor superfamily member 15 (TNFSF15) and evaluate their effects on the risk of developing gastric
adenocarcinoma. Forty
DNA samples from healthy volunteers were sequenced to identify single nucleotide polymorphisms (SNPs) in the TNFSF15 promoter. Two TNFSF15 SNPs (-358 T > C and -638 A > G) were identified by direct sequencing. Next, genotypes and haplotypes of 470 gastric
adenocarcinoma patients and 470
cancer-free controls were analyzed. Odds ratios (
ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Serologic tests for Helicobacter pylori
infection were measured by
enzyme-linked immuno-sorbent assay (ELISA). Subjects carrying the TNFSF15 -358 CC genotype were at an elevated risk for developing gastric
adenocarcinoma, compared with those with the -358 TT genotype (OR 1.42, 95% CI, 1.10 to 2.03). H. pylori
infection was a risk factor for developing gastric
adenocarcinoma (OR 2.31, 95% CI, 1.76 to 3.04). In the H. pylori infected group, subjects with TNFSF15 -358 CC genotype were at higher risks for gastric
adenocarcinoma compared with those carrying -358 TT genotype (OR: 2.01, 95%CI: 1.65 to 4.25), indicating that H. pylori
infection further influenced gastric
adenocarcinoma susceptibility. The -358 T>C polymorphism eliminates a
nuclear factor Y (NF-Y) binding site and the -358 C containing haplotypes showed significantly decreased
luciferase expression compared with -358 T containing haplotypes. Collectively these findings indicate that functional genetic variants in TNFSF15 may play a role in increasing susceptibility to gastric
adenocarcinoma.