Genotype Difference of Aldehyde Dehydrogenase 2 Gene in Alcohol Drinkers Influences the Incidence of Japanese Colorectal Cancer Patients

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Abstract
A case-control study was conducted to explore the possible etiologic role of alcohol and aldehyde dehydrogenase 2 (ALDH2) gene among Japanese colorectal cancer patients. Information on their drinking, smoking and dietary habits was collected from 265 colon and 164 rectum cancer patients, and 794 non-cancer patients as a control group. Genotypes of the ALDH2 gene at codon 487, glutamic acid (ALDH2*1) as a wild-type or lysine (ALDH2*2) as a mutated type with reduced enzyme activity, were analyzed by polymerase chain reaction in 160 colon and 110 rectum cancer patients and 121 control persons. Univariate analysis with the chi 2 statistical test showed that heavy alcohol drinking (P < 0.01), frequent meat intake (P < 0.001), and irregular (P < 0.01), hasty (P < 0.01) and excessive (P < 0.001) eating habits were associated with the incidence of both colon and rectum cancers, whereas heavier smoking (P < 0.05) and infrequent fish (P < 0.03) and fruit (P < 0.01) intake were solely associated with incidence of rectum cancer. Infrequent green vegetable intake was not correlated with the incidence of colorectal cancer. Multivariate unconditional logistic regression analysis confirmed the association of alcohol consumption (P < 0.01) and meat intake (P < 0.05). Homozygous and heterozygous carriers of ALDH2*2 allele tended to be found in colon (trend P = 0.04) but not in rectum cancer patients compared to controls. Risk elevation for colon cancer due to alcohol consumption was pronounced among the heterozygotes and it was statistically significant especially for distal colon cancer (trend P = 0.02). We conclude that alcohol consumption is a risk factor for colorectal cancer and the risk can be enhanced in ALDH2 heterozygotes.