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Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population.

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Date
2016-04
Authors
Zhu, Jinhong
Wang, Mengyun
He, Jing
Zhu, Meiling
Wang, Jiu-Cun
Jin, Li
Wang, Xiao-Feng
Yang, Ya-Jun
Xiang, Jia-Qing
Wei, Qingyi
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Abstract
Ethnic Han Chinese are at high risk of developing oesophageal squamous cell carcinoma (ESCC). Aberrant activation of the AKT signalling pathway is involved in many cancers, including ESCC. Some single nucleotide polymorphisms (SNPs) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNPs in AKT1 (rs2494750, rs2494752 and rs10138277) and AKT2 (rs7254617 and rs2304186) genes and investigated their associations with ESCC risk in 1117 ESCC cases and 1096 controls in an Eastern Chinese population. None of individual SNPs exhibited an association with ESCC risk. However, the combined analysis of three AKT1 SNPs suggested that individuals carrying one of AKT1 variant genotypes had a decreased ESCC risk [adjusted odds ratio (OR) = 0.60, 95% CI = 0.42-0.87]. Further stratified analysis found that AKT1 rs2294750 SNP was associated with significantly decreased ESCC risk among women (adjusted OR = 0.63, 95% CI = 0.43-0.94) and non-drinkers (OR = 0.79, 95% CI = 0.64-0.99). Similar protective effects on women (adjusted OR = 0.56, 95% CI = 0.37-0.83) and non-drinker (adjusted OR = 0.75, 95% CI = 0.60-0.94) were also observed for the combined genotypes of AKT1 SNPs. Consistently, logistic regression analysis indicated significant gene-gene interactions among three AKT1 SNPs (P < 0.015). A three-AKT1 SNP haplotype (C-A-C) showed a significant association with a decreased ESCC risk (adjusted OR = 0.70, 95% CI = 0.52-0.94). Multifactor dimensionality reduction analysis confirmed a high-order gene-environment interaction in ESCC risk. Overall, we found that three AKT1 SNPs might confer protection against ESCC risk; nevertheless, these effects may be dependent on other risk factors. Our results provided evidence of important gene-environment interplay in ESCC carcinogenesis.
Type
Journal article
Subject
Humans
Carcinoma, Squamous Cell
Esophageal Neoplasms
Odds Ratio
Risk Factors
Case-Control Studies
Gene Expression
Haplotypes
Polymorphism, Single Nucleotide
Aged
Middle Aged
China
Female
Male
Proto-Oncogene Proteins c-akt
Multifactor Dimensionality Reduction
Gene-Environment Interaction
Permalink
https://hdl.handle.net/10161/18000
Published Version (Please cite this version)
10.1111/jcmm.12750
Publication Info
Zhu, Jinhong; Wang, Mengyun; He, Jing; Zhu, Meiling; Wang, Jiu-Cun; Jin, Li; ... Wei, Qingyi (2016). Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population. Journal of cellular and molecular medicine, 20(4). pp. 666-677. 10.1111/jcmm.12750. Retrieved from https://hdl.handle.net/10161/18000.
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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