Genetic polymorphisms in the tobacco smoke carcinogens detoxifying enzyme UGT1A7 and the risk of head and neck cancer.
BACKGROUND
UGT1A7 is an enzyme involved in the metabolism of (pre)carcinogens present in tobacco smoke. We investigated whether genetic polymorphisms in UGT1A7, with predicted altered enzyme activity, may have a risk-modifying effect on head and neck carcinogenesis.


METHODS
Blood samples from 427 patients with oral, pharyngeal, and laryngeal carcinoma and 420 healthy control subjects were investigated for UGT1A7 polymorphisms. Based on these polymorphisms, patients and controls were divided according to predicted enzyme activity (low, intermediate, high).


RESULTS
Logistic regression analysis showed a significant increased distribution of predicted high activity UGT1A7 polymorphisms among the patients (OR:1.44; 95% CI: 1.07-1.93). Stratified analyses demonstrated that high activity UGT1A7 polymorphisms were even more significantly present in patients with laryngeal cancer, older patients, heavy smokers, and heavy drinkers when compared with the control subjects.


CONCLUSIONS
Predicted high activity UGT1A7 polymorphisms were significantly associated with an increased risk of head and neck cancer.
Lacko
Martin
M
Department of Otorhinolaryngology, Head and Neck Surgery, University Medical Center Maastricht, Maastricht, The Netherlands. martin.lacko@mumc.nl
Roelofs
Hennie M J
HM
te Morsche
Rene H M
RH
Voogd
Adri C
AC
Ophuis
Michael B Oude
MB
Peters
Wilbert H M
WH
Manni
Johannes J
JJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000428:Alcohol Drinking / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D014453:Glucuronosyltransferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007822:Laryngeal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D010610:Pharyngeal Neoplasms / Q000201:enzymology / Q000453:epidemiology / Q000235:genetics; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012906:Smoke / Q000032:analysis; D012907:Smoking / Q000453:epidemiology
D012906:Smoke; D014453:Glucuronosyltransferase; C524630:UGT1A7 protein, human