Aldehyde dehydrogenase 2 (ALDH2) and alcohol dehydrogenase 1B (ADH1B) polymorphisms exacerbate bladder cancer risk associated with alcohol drinking: gene-environment interaction.

Abstract

Although a range of chemical exposures (cigarette smoking and occupational exposure) are recognized risk factors for the development of bladder cancer (BCa), many epidemiological studies have demonstrated that alcohol drinking is not associated with BCa risk. Aldehyde dehydrogenase 2 (ALDH2; rs671, Glu504Lys) and alcohol dehydrogenase 1B (ADH1B; rs1229984, His47Arg) polymorphisms impact the accumulation of acetaldehyde, resulting in an increased risk of various cancers. To date, however, no studies evaluating the association between BCa risk and alcohol drinking have considered these polymorphisms. Here, we conducted a matched case-control study to investigate whether ALDH2 and ADH1B polymorphisms influence BCa risk associated with alcohol drinking. Cases were 74 BCa patients and controls were 740 first-visit outpatients without cancer at Aichi Cancer Center Hospital between January 2001 and December 2005. Odds ratio (OR), 95% confidence interval (CI) and gene-environment interaction were assessed by conditional logistic regression analysis with adjustment for potential confounders. Results showed that ALDH2 Glu/Lys was associated with a significantly increased risk of BCa compared with Glu/Glu (OR 2.03, 95% CI 1.14-3.62, P = 0.017). In contrast, ALDH2 Glu/Lys showed no increase in risk among the stratum of never drinkers compared with Glu/Glu, indicating a gene-environment interaction. ADH1B His/Arg had an OR of 1.98 (1.20-3.24, P = 0.007) compared with His/His. ADH1B Arg+ showed a similar OR and 95% CI. Individuals with ALDH2 Glu/Lys and ADH1B Arg+ had the highest risk of BCa compared with ALDH2 Glu/Glu and ADH1B His/His [OR 4.00 (1.81-8.87), P = 0.001].

• Authors: Hiroyuki Masaoka, Hidemi Ito, Norihito Soga, Satoyo Hosono, Isao Oze, Miki Watanabe, Hideo Tanaka, Akira Yokomizo, Norio Hayashi, Masatoshi Eto, Keitaro Matsuo
• Journal: Carcinogenesis (Carcinogenesis) Vol. 37 Issue 6 Pg. 583-588 (06 2016) ISSN: 1460-2180 [Electronic] England
• PMID: 26992901 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].

Chemical References

• ADH1B protein, human
• Alcohol Dehydrogenase
• ALDH2 protein, human
• Aldehyde Dehydrogenase, Mitochondrial

Topics

• Adult
• Aged
• Alcohol Dehydrogenase (genetics)
• Alcohol Drinking (adverse effects, genetics)
• Aldehyde Dehydrogenase, Mitochondrial (genetics)
• Asian People (genetics)
• Case-Control Studies
• Female
• Gene-Environment Interaction
• Genetic Predisposition to Disease
• Humans
• Male
• Middle Aged
• Polymorphism, Single Nucleotide
• Urinary Bladder Neoplasms (genetics)
• Young Adult