Combined effect of genetic polymorphisms in phase I and II biotransformation enzymes on head and neck cancer risk.
BACKGROUND
Combinations of genetic polymorphisms in biotransformation enzymes might modify the individual risk for head and neck cancer.


METHODS
Blood from 432 patients with head and neck cancer and 437 controls was investigated for genetic polymorphisms in 9 different phase I and II biotransformation enzymes. Analysis of the risk-modifying effect was performed according to predicted enzyme activities, based on genetic polymorphisms in the corresponding genes.


RESULTS
Combination of polymorphisms in COX-2 or EPHX1 with high activity polymorphisms in UGT1A1, UGT1A6, or UGT1A7 showed a risk-modulating effect in head and neck carcinogenesis, especially among heavy smokers and patients with laryngeal cancer. However, no additional effect for the combination of these polymorphisms was discovered when compared to the impact of polymorphism in UGT1A1, UGT1A6, and UGT1A7 individually.


CONCLUSIONS
Predicted high activity polymorphisms in the phase II enzymes UGT1A1, UGT1A6, and UGT1A7 are associated with an increased risk of head and neck cancer.
Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands. martin.lacko@mumc.nl
Martin
M
Lacko
Adri C
AC
Voogd
Hennie M J
HM
Roelofs
Rene H M
RH
te Morsche
Michel B
MB
Oude Ophuis
Wilbert H M
WH
Peters
Johannes J
JJ
Manni
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D014453:Glucuronosyltransferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects; D055815:Young Adult; D000099148:UGT1A1 Enzyme
D051546:Cyclooxygenase 2; D004851:Epoxide Hydrolases; D014453:Glucuronosyltransferase; D000099148:UGT1A1 Enzyme; C496540:PTGS2 protein, human; C110655:UDP-glucuronosyltransferase, UGT1A6; C491474:UGT2B7 protein, human; C454320:UDP-glucuronosyltransferase, UGT1A8; C524630:UGT1A7 protein, human; C486404:UGT2B4 protein, human; C522330:EPHX1 protein, human