Gene-environment interaction between an aldehyde dehydrogenase-2 (ALDH2) polymorphism and alcohol consumption for the risk of esophageal cancer

Abstract

Aldehyde dehydrogenase-2 (ALDH2) degrades acetaldehyde metabolized from ethanol. Its encoding gene ALDH2 has a functional polymorphism: ALDH2 Glu487LYS: An association between this polymorphism and esophageal cancer among alcoholics has been reported. To further evaluate the gene-environment interaction, a hospital-based case-control study was conducted. Cases were 102 patients with histologically confirmed esophageal cancer and controls were 241 non-cancer outpatients of Aichi Cancer Center. ALDH2 genotypes were examined by a PCR-CTPP method developed in our laboratory, which does not require a digestion stage. Logistic regression analysis was employed for estimation of relative risk and gene-environment interaction. The allele frequency for ALDH2 Lys487 was 0.28, consistent with previous reports. The age, sex, smoking and drinking status adjusted odds ratio for the ALDH2 Glu/Lys and Lys/Lys genotypes as compared with the Glu/Glu genotype was 3.43 (95% CI 1.74-6.75). The odds ratio for heavy drinking was 49.6 (14.5-169.4) among Lys487 carriers and 7.84 (2.77-22.2) for the Glu/Glu genotype. The gene-environment interaction between alcohol drinking and the ALDH2 Lys487 allele was 6.84 (2.39-19.6), whereas no significant interaction was obtained with smoking status. Although limited because of its prevalent case-control design, our study revealed a strong gene-environment interaction between ALDH2 polymorphism and heavy alcohol consumption. Taking the observed high risk of esophageal cancer in association with the ALDH2 Lys487 allele into consideration, reducing alcohol intake may be most protective among Lys487 allele carriers of this polymorphism.

Dietary selenium intake, aldehyde dehydrogenase‐2 and X‐ray repair cross‐complementing 1 genetic polymorphisms, and the risk of esophageal squamous cell carcinoma

“…The frequencies of the ALDH2 Glu allele (wild-type) and the ALDH2 Lys allele (varianttype) in healthy controls were 75% and 25%, respectively, consistent with a previous study in an Asian population. 21 Compared with individuals who had the ALDH2 Glu/Glu or ALDH2 Glu/Lys genotypes, the crude OR for the ALDH2 Lys/Lys genotype was 2.60 (95% CI, 1.41-4.80), and the adjusted OR was 1.91 (95% CI, 0.96-3.80). The frequencies of the XRCC1 399Arg allele (wild-type) and the Gln allele (variant) were 61.5% and 38.5%, respectively, in the control group.…”

“…23 Individuals with the ALDH2 Lys allele may have a high concentration of blood acetaldehyde after drinking alcohol. 24 The ALDH2 glutamic acid (Glu)/lysine (Lys) genotype, which encodes inactive ALDH2, enhances the risk for esophageal cancer in East Asian alcoholics. 25 Excessive alcohol consumption among smokers has been associated with an elevated risk of esophageal cancer.…”

Relationship between genetic polymorphisms of metabolizing enzymes CYP2E1, GSTM1 and Kazakh’s esophageal squamous cell cancer in Xinjiang, China

“…Cancer susceptible genes include types I and II metabolism enzyme genes, DNA repair gene and those affecting cell proliferation rate. In recent years, the evidence has been accumulated to support the hypothesis that cancer susceptible genes may be of importance in determining individual susceptibility to cancer [14][15][16][17][18][19] . EC is a disease determined by multi-factors, including environmental risk factors and genetic factors.…”

Alcohol dehydrogenase-2 and aldehyde dehydrogenase-2 genotypes, alcohol drinking and the risk for esophageal cancer in a Chinese population

“…3 Most studies, conducted mainly in Japan, have revealed associations between the ADH2 or ALDH2 polymorphism and esophageal cancer risk. [4][5][6][7][8] Chao et al 9 found that Chinese alcoholic patients with the ADH2 G and ALDH2 A alleles were more susceptible to esophageal cancer. Wu et al 10 also found a multiplicative effect of lifetime alcoholic consumption and genotypes (ADH2 and ALDH2) on esophageal cancer risk, but those were only found in Taiwanese males.…”