UDP-glucuronosyltransferase 1A1 (UGT1A1) is an
enzyme which catalyses not only the glucuronidation of tobacco
smoke carcinogens like benzopyrene, but also of the endogenous substrate
bilirubin.
Bilirubin for a long time was considered to be only a toxic
waste product of
hemoglobin degradation, but recent findings have shown that
bilirubin is a potent
antioxidant, which may play a protective role against
cancer. We investigated whether a genetic polymorphism in UGT1A1 (UGT1A1*28), associated with a reduced
UGT1A1 enzyme activity, may have a risk-modifying effect on head and neck
carcinogenesis. Blood samples from 421 patients with oral, pharyngeal or laryngeal
carcinoma, and 417 healthy controls were investigated for the UGT1A1*28 polymorphism. On the basis of the occurrence of this polymorphism, patients and controls were divided according to predicted
UGT1A1 enzyme activity (low, intermediate, high). Logistic regression analysis showed a significant increased distribution of predicted high activity UGT1A1*1 polymorphisms among the patients (OR: 1.37; 95% CI: 1.02-1.83). Stratified analyses demonstrated that predicted high activity UGT1A1 polymorphisms were present even more significantly in patients with
laryngeal cancer, older patients, heavy smokers and heavy drinkers. In conclusion, the predicted high activity UGT1A1*1 polymorphism, which results in lower serum levels of the
endogenous antioxidant bilirubin, was associated with an increased risk of
head and neck cancer.