Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.

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 nucl...

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Main Authors: Zhi Zhang, Dianke Yu, Jie Lu, Kan Zhai, Lei Cao, Juan Rao, Yingwen Liu, Xuemei Zhang, Yongli Guo
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4176965?pdf=render
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author Zhi Zhang
Dianke Yu
Jie Lu
Kan Zhai
Lei Cao
Juan Rao
Yingwen Liu
Xuemei Zhang
Yongli Guo
author_facet Zhi Zhang
Dianke Yu
Jie Lu
Kan Zhai
Lei Cao
Juan Rao
Yingwen Liu
Xuemei Zhang
Yongli Guo
author_sort Zhi Zhang
collection DOAJ
description 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.
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spelling doaj.art-7cd8fc41e8b948c996dc6b53af77fddb2022-12-21T17:45:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0199e10832110.1371/journal.pone.0108321Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.Zhi ZhangDianke YuJie LuKan ZhaiLei CaoJuan RaoYingwen LiuXuemei ZhangYongli GuoThe 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.http://europepmc.org/articles/PMC4176965?pdf=render
spellingShingle Zhi Zhang
Dianke Yu
Jie Lu
Kan Zhai
Lei Cao
Juan Rao
Yingwen Liu
Xuemei Zhang
Yongli Guo
Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
PLoS ONE
title Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
title_full Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
title_fullStr Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
title_full_unstemmed Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
title_short Functional genetic variants of TNFSF15 and their association with gastric adenocarcinoma: a case-control study.
title_sort functional genetic variants of tnfsf15 and their association with gastric adenocarcinoma a case control study
url http://europepmc.org/articles/PMC4176965?pdf=render
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