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Potentially functional polymorphisms in the CASP7 gene contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population.

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Date
2013-01
Authors
Wang, Meng-Yun
Zhu, Mei-Ling
He, Jing
Shi, Ting-Yan
Li, Qiao-Xin
Wang, Ya-Nong
Li, Jin
Zhou, Xiao-Yan
Sun, Meng-Hong
Wang, Xiao-Feng
Yang, Ya-Jun
Wang, Jiu-Cun
Jin, Li
Wei, Qing-Yi
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Abstract
BACKGROUND: Caspase 7 (CASP7) is an important regulator and executioner in the apoptosis pathway and plays a crucial role in cancer development and progression. However, few studies have evaluated associations between functional single nucleotide polymorphisms (SNPs) in the 3' untranslational region (UTR) of CASP7 and risk of gastric cancer. METHODS: In a case-control study of 1117 patients with gastric cancer and 1146 cancer-free controls with frequency matching on age and sex, we genotyped four potentially functional SNPs (rs4353229T>C, rs10787498T>G, rs1127687G>A and rs12247479G>A) located in the microRNA binding sites of the CASP7 3' UTR by using Taqman assays and evaluated their associations with risk of gastric cancer by using logistic regression analyses as well as multifactorial dimension reduction (MDR) analysis. RESULTS: In the single-locus analysis, only the CASP7 rs4353229 TT genotype was associated with 0.83-fold decreased risk (95% confidence interval [CI] = 0.70-0.98) of gastric cancer under a recessive model, compared with the CT/CC genotypes. In the combined analysis of all four SNPs, we found that the risk of gastric cancer decreased by 19% in those carrying any of the risk genotypes (adjusted odds ratio = 0.81, 95% CI = 0.68-0.96), compared with those carrying zero risk genotypes, and this risk was more evident in subgroups of younger age (<59 years), females, non-smokers, non-drinkers and patients with non-gastric cardia adenocarcinoma. Further MDR analysis suggested some evidence of interactions between the combined genotypes and other risk factors for gastric cancer. CONCLUSIONS: Potentially functional CASP7 variants may contribute to risk of gastric cancer. Larger studies with different ethnic populations are warranted to validate our findings.
Type
Journal article
Subject
Cell Line, Transformed
Humans
Adenocarcinoma
Stomach Neoplasms
Genetic Predisposition to Disease
RNA, Messenger
Prognosis
Case-Control Studies
Gene Frequency
Gene Order
Genotype
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Alleles
Adult
Aged
Aged, 80 and over
Middle Aged
Asian Continental Ancestry Group
China
Female
Male
Caspase 7
Young Adult
Permalink
https://hdl.handle.net/10161/17994
Published Version (Please cite this version)
10.1371/journal.pone.0074041
Publication Info
Wang, Meng-Yun; Zhu, Mei-Ling; He, Jing; Shi, Ting-Yan; Li, Qiao-Xin; Wang, Ya-Nong; ... Wei, Qing-Yi (2013). Potentially functional polymorphisms in the CASP7 gene contribute to gastric adenocarcinoma susceptibility in an eastern Chinese population. PloS one, 8(9). pp. e74041. 10.1371/journal.pone.0074041. Retrieved from https://hdl.handle.net/10161/17994.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Wei

Qingyi Wei

Professor in Population Health Sciences
Qingyi Wei, MD, PhD, Professor in the Department of Medicine, is Associate Director for Cancer Control and Population Sciences, Co-leader of CCPS and Co-leader of Epidemiology and Population Genomics (Focus Area 1). He is a professor of Medicine and an internationally recognized epidemiologist focused on the molecular and genetic epidemiology of head and neck cancers, lung cancer, and melanoma. His research focuses on biomarkers and genetic determinants for the DNA repair deficient phenotype and
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