Prevalence of alcohol dehydrogenase 1B and aldehyde dehydrogenase 2 genotypes in Kashmir, an Asian high-risk region of esophageal squamous cell carcinoma

Alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) are the two essential enzymes for alcohol metabolism. Polymorphic variants in these genes have been linked with an elevated risk of some alcohol-related cancers, including oesophageal squamous cell carcinoma (ESCC). In the current study, we aimed to evaluate the distribution of ADH1B (p.His48Arg; rs1229984) and ALDH2 (p.Glu504Lys; rs671) genotypes and investigate the association of these variants with the ESCC risk in Kashmir, India, a region where ESCC is comparatively more prevalent. We analyzed ADH1B and ALDH2 genotypes in 340 histopathologically verified ESCC cases and 800 controls by polymerase chain reaction with confronting two-pair primer (PCR-CTPP) and direct sequencing. To assess the association of the genotypes with ESCC risk, we used conditional logistic regression models. The frequency of mutant ADH1B 48His (ADH1B*) and ALDH2 504Lys (ALDH2*2) alleles was 29.0% and 1.9% respectively in controls. The odds ratio (OR) for the association between the genotypes ALDH2*1/*2, compared to *1/*1, and ESCC risk was above the unity, whereas it was below unity for ALDH2 *2/*2. However, due to a modest number of individuals with variant genotypes in the ALDH2 gene, 95% confidence intervals (Cis) for their associations with ESCC risk could not be calculated in the adjusted models. The corresponding OR (95% CI) was 0.87 (0.45 – 1.69) for ADH1B*2/*2 and 4.61 (0.20 –105.86) for ADH1B*1/*2. The lack of association between studied ADH1B and ALDH2 polymorphic variants and ESCC risk in Kashmir may be supported by the low prevalence of the mutant alleles, which is much lower than the reported prevalence in Chinese and Japanese populations, and low alcohol drinking in the Kashmiri population.