Polymorphisms in metabolizing enzymes and the risk of head and neck squamous cell carcinoma in the Slavic population of the central Europe.
The question of susceptibility to squamous cell carcinoma of head and neck (SCCHN) in the environmental context was addressed by analysis of functional polymorphisms in enzymes metabolizing smoke constituents and/or alcohol (CYP2A13, CYP1B1, EPHX1, NQO1, GSTM1, GSTP1, GSTT1, ADH1B and ADH1C). Case-control study of 122 age- and sex-matched pairs of subjects was performed using so far unexplored Central European Slavic population with high level of tobacco and alcohol abuse. Age-, gender-, smoking- and alcohol-adjusted logistic regression failed to demonstrate any significant association of the analyzed polymorphisms with the SCCHN risk. When interactions between potential modifiers of effect, i.e. smoking and alcohol were tested, drinkers seemed to be at lower risk than nondrinkers when carrying the heterozygous genotype Ile/Val in codon 432 of CYP1B1 (OR=0.42; 95% CI=0.21-0.83; p=0.013 vs. OR=1.02; 95% CI=0.34-2.94; p=0.977). Similarly, drinkers were at lower risk than nondrinkers when carrying the heterozygous genotype Pro/Ser in codon 187 of NQO1 (OR=0.41; 95% CI=0.19-0.88; p=0.022 vs. OR=0.96; 95% CI=0.29-3.12; p=0.948). More interestingly, drinkers carrying the rare homozygous genotype Val/Val in codon 350 of ADH1C were at significantly higher risk than nondrinkers carrying this genotype (OR=4.01; 95% CI=1.61-10.01; p=0.003 vs. OR=0.93; 95% CI=0.25-3.57; p=0.919). This result confirmed findings of previously published studies. Smoking did not significantly modify the effect of genotypes. Our data thus demonstrate that genetic susceptibility to SCCHN shall be further followed on populations with different genetic background and lifestyle.
Soucek
P
P
National Institute of Public Health, Prague, Czech Republic. psoucek@szu.cz
Susova
S
S
Mohelnikova-Duchonova
B
B
Gromadzinska
J
J
Moraviec-Sztandera
A
A
Vodicka
P
P
Vodickova
L
L
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000426:Alcohol Dehydrogenase / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005060:Europe / Q000453:epidemiology; D005260:Female; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics; D011110:Polymorphism, Genetic; D012306:Risk; D012907:Smoking
D003577:Cytochrome P-450 Enzyme System; C420272:ADH1C protein, human; D000426:Alcohol Dehydrogenase; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human