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

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 χ χ χ χ 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.

Dairy products and colorectal cancer. A review of possible mechanisms and epidemiological evidence

“…The ORs for the highest category of consumption vs the lowest are summarized in Figure 1. Out of 11 case -control studies, three found a significant risk increase (Benito et al, 1990;Iscovich et al, 1992;Steinmetz & Potter, 1993) and three other studies a significantly decreased risk (Shannon et al, 1996;Kampman et al, 2000;Murata et al, 1999). The diversity of dairy products may to some extent explain the inconsistencies of these results.…”

Meta-analysis of the ADH1B and ALDH2 Polymorphisms and the Risk of Colorectal Cancer in East Asians

“…However, the results have been inconsistent (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). The present comprehensive meta-analysis of currently published studies aimed to identify the relationships between the ADH1B and ALDH2 polymorphisms and the risk of CRC.…”

Aldehyde Dehydrogenase 3B1 (ALDH3B1): Immunohistochemical Tissue Distribution and Cellular-specific Localization in Normal and Cancerous Human Tissues

“…Indeed, low ALDH levels in the colon lead to the highest acetaldehyde exposure of any tissue during ethanol metabolism, which is believed to be a factor in alcohol-related colon cancer (Salaspuro 1996). ALDH2-mediated metabolism of acetaldehyde is a major detoxification route, and carriers of the ALDH2*2 polymorphism, which confers loss of ALDH2 enzymatic activity, have increased risk for alcohol-related colon cancer (Murata et al 1999) and smoke-and alcohol-related lung cancer (Minegishi et al 2007;Eom et al 2009). Although acetaldehyde itself is poorly metabolized by ALDH3B1, downstream LPO-derived aldehydes, including the highly cytotoxic 4-HNE, appear to be good substrates (Marchitti et al 2007b).…”