Open AccessPolymorphisms in the AKT 1 and AKT 2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population
Author(s) -
Zhu Jinhong,
Wang Mengyun,
He Jing,
Zhu Meiling,
Wang JiuCun,
Jin Li,
Wang XiaoFeng,
Yang YaJun,
Xiang JiaQing,
Wei Qingyi
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12750
Subject(s) - single nucleotide polymorphism , odds ratio , genotype , haplotype , snp , akt1 , medicine , biology , oncology , population , genetics , gene , protein kinase b , apoptosis , environmental health
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 ( SNP s) in genes involved in this pathway may contribute to ESCC susceptibility. We selected five potentially functional SNP s in AKT 1 (rs2494750, rs2494752 and rs10138277) and AKT 2 (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 SNP s exhibited an association with ESCC risk. However, the combined analysis of three AKT 1 SNP s suggested that individuals carrying one of AKT 1 variant genotypes had a decreased ESCC risk [adjusted odds ratio ( OR ) = 0.60, 95% CI = 0.42–0.87]. Further stratified analysis found that AKT 1 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 AKT 1 SNP s. Consistently, logistic regression analysis indicated significant gene–gene interactions among three AKT 1 SNP s ( P < 0.015). A three‐ AKT 1 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 AKT 1 SNP s 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.