Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population.
Polymorphisms in the AKT1 and AKT2 genes and oesophageal squamous cell carcinoma risk in an Eastern Chinese population.
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中国东部人群 AKT1 和 AKT2 基因多态性与食管鳞状细胞癌风险
DOI：
10.1111/jcmm.12750
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发表时间：
2016-04
影响因子：
5.3
通讯作者：
Wei Q
中科院分区：
文献类型：
--
作者：
Zhu J;Wang M;He J;Zhu M;Wang JC;Jin L;Wang XF;Yang YJ;Xiang JQ;Wei Q
汉族是食道鳞状细胞癌（ESCC）的高危人群。AKT信号通路的异常激活涉及许多癌症，包括ESCC。一些参与该通路的基因的单核苷酸多态性（snp）可能与ESCC易感性有关。我们选择了AKT1 （rs2494750、rs2494752和rs10138277）和AKT2 （rs7254617和rs2304186）基因中的5个潜在功能snp，并在中国东部人群的1117例ESCC病例和1096例对照中研究了它们与ESCC风险的关系。没有单个snp显示与ESCC风险相关。然而，对三个AKT1 snp的联合分析表明，携带AKT1变异基因型之一的个体患ESCC的风险降低[校正优势比(OR) = 0.60, 95% CI = 0.42-0.87]。进一步的分层分析发现，AKT1 rs2294750 SNP在女性（校正OR = 0.63, 95% CI = 0.43-0.94）和非饮酒者（OR = 0.79, 95% CI = 0.64-0.99）中显著降低ESCC风险相关。AKT1 snp的组合基因型对女性（校正OR = 0.56, 95% CI = 0.37-0.83）和非饮酒者（校正OR = 0.75, 95% CI = 0.60-0.94）也有类似的保护作用。逻辑回归分析结果显示，三个AKT1 snp之间存在显著的基因相互作用（P < 0.015）。3‐AKT1 SNP单倍型（C‐A‐C）显示与ESCC风险降低显著相关（校正OR = 0.70, 95% CI = 0.52-0.94）。多因素降维分析证实了ESCC风险的高阶基因-环境相互作用。总的来说，我们发现三个AKT1 snp可能对ESCC风险具有保护作用；然而，这些影响可能取决于其他风险因素。我们的研究结果为ESCC的癌变提供了重要的基因-环境相互作用的证据。
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.
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