Polymorphisms in alcohol metabolism genes ADH1B and ALDH2, alcohol consumption and colorectal cancer. Academic Article uri icon

Overview

MeSH

  • Acetaldehyde
  • Aldehyde Dehydrogenase, Mitochondrial
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Metabolic Networks and Pathways
  • Oxidation-Reduction
  • Risk Factors

MeSH Major

  • Alcohol Dehydrogenase
  • Alcohol Drinking
  • Aldehyde Dehydrogenase
  • Colorectal Neoplasms
  • Ethanol
  • Polymorphism, Single Nucleotide

abstract

  • 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. 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. 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.

publication date

  • 2013

has subject area

  • Acetaldehyde
  • Alcohol Dehydrogenase
  • Alcohol Drinking
  • Aldehyde Dehydrogenase
  • Aldehyde Dehydrogenase, Mitochondrial
  • Colorectal Neoplasms
  • Ethanol
  • Genotype
  • Humans
  • Logistic Models
  • Male
  • Metabolic Networks and Pathways
  • Oxidation-Reduction
  • Polymorphism, Single Nucleotide
  • Risk Factors

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3839967

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0080158

PubMed ID

  • 24282520

Additional Document Info

start page

  • e80158

volume

  • 8

number

  • 11