Polymorphisms in Alcohol Metabolism Genes <i>ADH1B</i> and <i>ALDH2</i>, Alcohol Consumption and Colorectal Cancer

<div><p>Background</p><p>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 <i>ADH1B</i> and <i>ALDH2</i> genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population.</p><p>Methodology/Principal Findings</p><p>SNPs from <i>ADH1B</i> and <i>ALDH2</i> 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 <i>ADH1B</i> 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 <i>ADH1B</i> gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption.</p><p>Conclusions/Significance</p><p>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.</p></div

Association between polymorphisms in alcohol metabolism genes and colorectal cancer risk (men only).

1<p>OR adjusted for age, ethnicity, religion, energy intake and physical activity.</p