Association between ALDH2 polymorphism and esophageal cancer risk in South Koreans: a case-control study

Abstract

Background Alcohol consumption is a major risk factor for esophageal cancer; however, a high incidence of esophageal cancer is observed particularly among Eastern Asians, although they consume relatively less alcohol, presumably due to the high frequency of aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms. Nevertheless, the association between ALDH2 polymorphisms and esophageal cancer remains under debate. In the present study, we evaluated the association between ALDH2 rs671 polymorphisms and the risk of esophageal cancer in the South Korean population. Methods This study included 783 hospital based-cases and 8732 population-based controls. Information on smoking history and alcohol consumption was obtained from the medical records or interview questionnaires. Age-adjusted logistic regression analysis was performed to assess the association between ALDH2 rs671 polymorphisms and esophageal cancer. Results Odds ratios (ORs) for esophageal cancer in men with GA and AA genotypes were 2.75 (95% confidence interval [CI]: 2.34–3.23) and 0.08 (95% CI: 0.00–0.35), respectively; whereas, in women, these ratios were 2.99 (95% CI: 1.43–6.34) and 6.18 (95% CI: 1.40–19.62), respectively, taking subjects with the ALDH2 GG genotype as a reference. In men, the association between ALDH2 polymorphisms and esophageal cancer was modified by alcohol consumption. Conclusion In Eastern Asians, ALDH2 rs671 polymorphisms are associated with esophageal cancer, which may be linked to acetaldehyde accumulation.

Risk for Esophageal Cancer Based on Lifestyle Factors–Smoking, Alcohol Consumption, and Body Mass Index: Insight from a South Korean Population Study in a Low-Incidence Area

“…Independently, the presence of higher concentrations of acetaldehyde in saliva, compared with blood, may constitute toxic alcohol-related acetaldehyde exposure because of the direct contact with the esophageal mucosa [48]. A substantial proportion, approximately 40-50%, of East Asians, including South Koreans [50], exhibit very low ALDH2 activity due to a specific single-nucleotide polymorphism in the coding region of ALDH2 that results in the substitution of lysine with glutamine at position 487, which subsequently increases their vulnerability to the carcinogenic effects of alcohol by elevating acetaldehyde exposure [49]. In genome-wide association studies, these genetic factors of multiple functional variants within ADH1B and ALDH2 genes that lead to heightened acetaldehyde levels after alcohol consumption may interact with environmental factors, particularly tobacco and alcohol use, and result in a significantly heightened risk of esophageal cancer-146.4 to 190 times higher than in individuals without these genetic and lifestyle risk factors [51,52].…”

Does genetic predisposition modify the effect of lifestyle-related factors on DNA methylation?

“…In the present study, we used an Australian cohort of European-ancestry, in which the allele frequencies of variants in these alcohol-metabolism genes were very low, most of them were < 1%. For instance, the ALDH2 rs671 polymorphism, which has been widely studied in Asian groups [52-54], was not included in our analyses due to very low MAF (< 0.1%). Therefore, the candidate gene approach focusing on single variants may not be appropriate in European-ancestry populations for this phenotypic trait, unless resources with a very large sample size are used.…”

No association between genetically predicted C-reactive protein levels and colorectal cancer survival in Korean: two-sample Mendelian randomization analysis

“…The CRC GWAS data were obtained from the Hwasun Cancer Epidemiology Study-Colon and Rectum Cancer (HCES-CRC). The Hwasun Cancer Epidemiology Study (HCES) is a hospital-based case-control study aiming to identify serologic and genetic risk factors for multiple cancers, including esophageal [ 30 ], breast [ 31 ], gastric [ 32 ], and colorectal cancers [ 33 ]. The HCES-CRC consisted of 7,089 hospital-based CRC cases and 4,979 populationbased cancer-free controls.…”