title: Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
abstract: 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.
authors.affiliation: Department of Chemotherapy and Radiotherapy, Tangshan Gongren Hospital, Tangshan, China; Institute of Molecular Genetics, College of Life Science, Hebei United University, Tangshan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Etiology of Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.affiliation: Beijing Key Laboratory for Pediatric Otolaryngology, Head and Neck Science, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of Etiology of Carcinogenesis, Cancer Institute, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Zhai
authors.affiliation: Institute of Molecular Genetics, College of Life Science, Hebei United University, Tangshan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Cao
authors.affiliation: Institute of Molecular Genetics, College of Life Science, Hebei United University, Tangshan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Rao
authors.affiliation: Institute of Molecular Genetics, College of Life Science, Hebei United University, Tangshan, China.
authors.forename: Yingwen
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Molecular Genetics, College of Life Science, Hebei United University, Tangshan, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Beijing Key Laboratory for Pediatric Otolaryngology, Head and Neck Science, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000382:microbiology*; D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies / Q000379:methods*; D016481:Helicobacter Infections / Q000235:genetics* / Q000382:microbiology; D016480:Helicobacter pylori / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics / Q000382:microbiology*; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15 / Q000235:genetics*
chemical_list: C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15