Polymorphisms in alcohol metabolizing genes and the risk of head and neck cancer in a Brazilian population.
OBJECTIVE
The incidence of head and neck cancer (HNC) in Brazil has increased substantially in recent years. This increase is likely to be strongly associated with alcohol and tobacco consumption, but genetic susceptibility also should be investigated in this population. The aim of this study was to evaluate the association of polymorphisms in genes of alcohol metabolism enzymes and the risk of HNC.


METHODS
A hospital-based case-control study was conducted in São Paulo, Brazil. We here investigated ADH1C Ile(350)Val, ADH1B Arg(48)His, ADH1B Arg(370)Cys and CYP2E1*5A PstI polymorphisms by PCR-RFLP Polymerase Chain Reaction - Restriction Fragment Length Polymorphism in 207 histopathologically confirmed HNC cases (184 males and 23 females) and 244 cancer-free controls (225 males and 19 females) admitted as in-patients in the same hospital.


RESULTS
Chronic alcohol intake increased approximately four times the risk of HNC. The mutant genotype ADH1B Arg(48)His was more frequent in controls (12.7%) than HNC patients (5.8%) conferring protection for the disease (odds ratio (OR) = 0.42; 95% confidence interval (CI ), 0.21-0.85). Similar results were observed for individuals with ADH1B*2 (OR = 0.41; 95% CI , 0.20-0.82) or ADH1B*2/ADH1C*1 (OR = 0.32; 95% CI , 0.13-0.79) mutated haplotypes. Multiple regression analyses showed that individuals with the mutant genotype ADH1B Arg(48)His who consume alcohol >30 g/L/day have more than four times the risk for HNC (OR = 4.42; 95% CI, 1.21-16.11).


CONCLUSIONS
The fast alcohol metabolizing genotypes may prevent HNC when the amount of alcohol intake is <30.655 g/L/day.
Garcia
Silvia Marçal Nunes
SM
Department of Legal Medicine, Bioethics and Occupational Health, School of Medicine, São Paulo, SP, Brazil.
Curioni
Otávio A
OA
de Carvalho
Marcos Brasilino
MB
Gattás
Gilka Jorge Figaro
GJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000235:genetics; D001938:Brazil; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics
C489332:ADH1B protein, human; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1