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


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.
Solomon
P R
PR
Department of Biochemistry, Centre for Advanced Studies in Functional Genomics, School of Biological Sciences, Madurai Kamaraj University, Madurai, India.
Selvam
G S
GS
Shanmugam
G
G
D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000009:adverse effects / Q000235:genetics; D000437:Alcoholism / Q000150:complications / Q000235:genetics*; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D042965:Methylenetetrahydrofolate Reductase (NADPH2)