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...
Main Authors: | , , , , , , , , |
---|---|
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 |
_version_ | 1819238423718789120 |
---|---|
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. |
first_indexed | 2024-12-23T13:36:00Z |
format | Article |
id | doaj.art-7cd8fc41e8b948c996dc6b53af77fddb |
institution | Directory Open Access Journal |
issn | 1932-6203 |
language | English |
last_indexed | 2024-12-23T13:36:00Z |
publishDate | 2014-01-01 |
publisher | Public Library of Science (PLoS) |
record_format | Article |
series | PLoS ONE |
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 |
work_keys_str_mv | AT zhizhang functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT diankeyu functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT jielu functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT kanzhai functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT leicao functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT juanrao functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT yingwenliu functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT xuemeizhang functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy AT yongliguo functionalgeneticvariantsoftnfsf15andtheirassociationwithgastricadenocarcinomaacasecontrolstudy |