Association between ALDH2 and ADH1B Polymorphisms and the Risk for Colorectal Cancer in Koreans.

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  • Additional Information
    • Source:
      Publisher: The Association Country of Publication: Korea (South) NLM ID: 101155137 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2005-9256 (Electronic) Linking ISSN: 15982998 NLM ISO Abbreviation: Cancer Res Treat Subsets: MEDLINE
    • Publication Information:
      Original Publication: Seoul, Korea : The Association,
    • Subject Terms:
      Alcohol Dehydrogenase/*genetics ; Alcohol Drinking/*epidemiology ; Aldehyde Dehydrogenase, Mitochondrial/*genetics ; Colorectal Neoplasms/*epidemiology; Aged ; Alcohol Dehydrogenase/metabolism ; Aldehyde Dehydrogenase, Mitochondrial/metabolism ; Asian People/genetics ; Case-Control Studies ; Causality ; Cohort Studies ; Colorectal Neoplasms/genetics ; Ethanol/metabolism ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Odds Ratio ; Polymorphism, Single Nucleotide ; Republic of Korea/epidemiology ; Risk Assessment/statistics & numerical data ; Risk Factors
    • Abstract:
      Purpose: Excessive alcohol consumption has been linked to an increased risk of colorectal cancer (CRC). We evaluated the association between alcohol-related genetic variants and CRC risk.
      Materials and Methods: The study cohort consisted of 5,435 CRC cases and 3,553 population-based cancer-free controls. Genotype data were generated from germline DNA using the Infinium OncoArray-500K BeadChip in 2,535 cases and 2,287 controls and the Infinium Multi-Ethnic Global BeadChip in 2,900 cases and 1,266 controls. The associations between aldehyde dehydrogenase 2 (ALDH2) rs671 and alcohol dehydrogenase 1B (ADH1B) rs1229984 polymorphisms and CRC risk were assessed using multivariate logistic regression analyses.
      Results: Compared with the major homozygous ALDH2 genotype (GG), heterozygous or minor homozygous ALDH2 genotype (GA or AA, related to a low alcohol consumption) was significantly associated with a reduced risk for CRC in men (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.68 to 0.90), but not in women (OR, 0.70; 95% CI, 0.47 to 1.05). A stronger association was found among regular drinkers (OR, 0.58; 95% CI, 0.47 to 0.71 in men and OR, 0.33; 95% CI, 0.18 to 0.58 in women). No association of CRC risk with ADH1B rs1229984 genotype was found. The association between alcohol-related combined genotypes and risk of CRC was significant (p for linear=0.001). The combined genotype with the highest genetically predicted alcohol consumption (ALDH2 rs671 GG and ADH1B rs1229984 AG/GG) was associated with a high risk for CRC (OR, 1.35; 95% CI, 1.11 to 1.63).
      Conclusion: Our study provides strong evidence for a possible causal association between alcohol consumption and CRC risk.
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    • Grant Information:
      R01 CA188214 United States CA NCI NIH HHS; R01CA188214 United States NH NIH HHS; 2017-2857 Chonnam National University; U19CA148107 United States NH NIH HHS; U19 CA148107 United States CA NCI NIH HHS
    • Contributed Indexing:
      Keywords: Alcohol; Alcohol dehydrogenase 2; Aldehyde dehydrogenase 2; Colorectal neoplasm
    • Accession Number:
      3K9958V90M (Ethanol)
      EC 1.1.1.1 (ADH1B protein, human)
      EC 1.1.1.1 (Alcohol Dehydrogenase)
      EC 1.2.1.3 (ALDH2 protein, human)
      EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial)
    • Publication Date:
      Date Created: 20210110 Date Completed: 20211217 Latest Revision: 20221207
    • Publication Date:
      20240829
    • Accession Number:
      PMC8291179
    • Accession Number:
      10.4143/crt.2020.478
    • Accession Number:
      33421985