Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population.
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 articleSubject
HumansCarcinoma, 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
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https://hdl.handle.net/10161/18000Published Version (Please cite this version)
10.1111/jcmm.12750Publication 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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Show full item recordScholars@Duke
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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