Polymorphism in ADH and MTHFR genes in oral squamous cell carcinoma of Indians

Objectives: Alcohol consumption is known to increase the risk for several cellular disorders like oral cancer. The risk may be reinforced by polymorphism in genes like alcohol dehydrogenase . Therefore, this study is designed to asses the polymorphic status in ADH1B (formerly ADH2 ), ADH1C (formerly ADH3 ) and MTHFR genes in order to correlate the susceptibility to oral squamous cell carcinoma (OSCC). Subjects and methods: DNA from 126 OSCC samples were amplified using primers for ADH1B , ADH1C and MTHFR genes. The amplicons were analyzed for ADH1B*1 , ADH1C*2 and MTHFR C677T allelic polymorphism by restriction digestion using appropriate enzymes. Results: ADH1B*1/*1 genotype in cancer patients who were heavy drinkers showed a negligible risk association with an odds ratio of 1.62; 95% CI = 1.08–2.14. In OSCC patients, ADH1C*2/*2 genotypes showed a relatively higher risk (odds ratio 2.65; 95% CI = 1.78–3.53) in heavy drinkers and a less significant risk (1.6; 95% CI = 1.15–2.03) in moderate drinkers and negligible risk in light drinkers (1.23; 95% CI = 0.77–1.63). In contrast, MTHFR 677TT genotype showed a high risk association for OSCC in heavy drinkers (odds ratio 3.0; 95% CI = 2.02–4.0). Interestingly, the combination of ADH1B*1/*1/ MTHFR 677TT genotypes in alcoholic cancer patients showed a high risk (odds ratio 4.16; 95% CI = 2.78–5.53). A similar risk (odds ratio 4.16; 95% CI = 1.18–5.53) was shown by ADH1B*1/*2/*2/*2MTHFR 677TT genotype combination. The ADH1C*2/*2 /MTHFR 677TT genotype combination showed the maximum risk (odds ratio 20; 95% CI = 13.45–26.64) in the heavy drinker group. This combination showed a high risk in moderate drinkers (odds ratio 5.88; 95% CI = 4.24–7.50) and relatively lower risk in light drinkers (odds ratio 2.77; 95% CI = 1.74–3.68). Conclusions: The ADH1C*2/*2/MTHFR 677TT genotype combination appears to be more susceptible for OSCC, since it showed a 20‐fold increase in risk in heavy drinkers and a 5.9‐ and 2.8‐fold increase in risk respectively in moderate drinkers and light drinkers. This study suggests the association of ADH1C*2/*2/MTHFR 677TT genotype combination as a risk factor for OSCC in alcoholics.