Comparison of Alcohol Dehydrogenase 2 and Aldehyde Dehyrdogenase 2 Polymorphism in Esophageal Cancer Cases vs Controls in Kashmir

The esophageal cancer (EC) is the most common cancer in Kashmir and its causes are not yet clearly understood. The current study was designed with the aim of understanding the association of known genotypes in ADH2 and ALDH2 genes and role of local dietary habits like consumption of salt tea, socioeconomic status and smoking with esophageal cancer risk. We analyzed 50 histopathologically confirmed esophageal cancer cases and same number of age, sex, and region matched nonmalignant controls. The data on dietary history/tobacco consumption/family history of cancer/fruit consumption and economic status was collected through a well drafted questionnaire. Male and female ratio among 50 esophageal cancer patients registered came out to be 1:1.63 which is contrary to the previously reported 1:2. Highest number of esophageal cases turned out from southern region of Kashmir. The low fruit consumption (86.0%), low socio-economic status (70.00%) and very frequent consumption of salt tea (98%) were the common features in our cases which can be strong risk factors for EC in valley. The family history of the subjects turned out to be another potential risk factor for EC in Kashmir as about 22.00% of cases have family history of cancer. Most of the cases (74.00%) were smokers which is an established risk factor for EC. The genetic analysis of the cases and controls by PCR-CTPP method, for the genotypic frequencies in ADH2 and ALDH2 genes revealed that unlike other high risk regions, Kashmiri population has a different standing. ADH2 allele that encodes ADH enzyme with high activity or ALDH2 allele that encodes ALDH enzyme with particularly low activity lead to the accumulation of acetaldehyde and increase the risk of developing esophageal cancer. In the present cohort of cases, SNPs in ADH2 and ALDH2 do not confer any risk of esophageal cancer development in Kashmir. The frequency of ADH2*2 and ALDH2*2 mutant alleles was found to be 39.5% and 5% respectively. The results when compared with the mutant allele frequencies of the other high risk regions of EC support the fact that the mutant alleles of the two genes are highly frequent in East Asia only and in the rest of the world their frequencies are low