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Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption and colorectal cancer

机译:酒精代谢基因ADH1B和ALDH2的多态性,饮酒与结直肠癌

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摘要

Background: Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in ADH1B and ALDH2 genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population. Methodology/Principal Findings: SNPs from ADH1B and ALDH2 genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in ADH1B gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of ADH1B gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption. Conclusions/Significance: Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants.
机译:背景:大肠癌(CRC)是全球癌症死亡的主要原因。 CRC的流行病学危险因素包括摄入酒精,酒精主要通过酒精脱氢酶代谢为乙醛,然后通过醛脱氢酶进一步氧化为乙酸盐。因此,基因在酒精代谢途径中的作用特别令人关注。这项研究的目的是分析ADH1B和ALDH2基因中的SNP与CRC风险之间的关联,以及饮酒对研究人群中CRC风险的主要影响。方法学/主要发现:在1694例CRC病例和1851例来自大肠癌分子流行病学研究的对照中,对酒精代谢途径中包括的ADH1B和ALDH2基因的SNP进行了基因分型。还获得了有关临床病理特征,生活方式和饮食习惯的信息。进行逻辑回归和关联分析。结肠直肠癌的分子流行病学研究(MECC)研究显示,男性参与者饮酒与CRC风险呈正相关(OR = 1.47; 95%CI = 1.18-1.81)。此外,发现ADH1B基因中的SNPs rs1229984与CRC风险有关:在隐性模型下,A / A基因型的OR为1.75(95%CI = 1.21-2.52; p值= 0.0025)。基于结构方程模型的路径分析显示,ADH1B基因多态性对结直肠癌发生有直接影响,而且还通过饮酒介导了间接影响。结论/意义:酒精代谢途径中的遗传多态性可能在结直肠癌发生中具有潜在作用,可能是由于这些酶变异体在乙醇代谢和乙醛氧化方面的差异。

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