Genetic polymorphisms in the tobacco smoke carcinogens detoxifying enzyme UGT1A7 and the risk of head and neck cancer

Head Neck. 2009 Oct;31(10):1274-81. doi: 10.1002/hed.21090.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alcohol Drinking / epidemiology
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics
  • Female
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics*
  • Glucuronosyltransferase / genetics*
  • Head and Neck Neoplasms / enzymology*
  • Head and Neck Neoplasms / epidemiology
  • Head and Neck Neoplasms / genetics
  • Humans
  • Laryngeal Neoplasms / enzymology
  • Laryngeal Neoplasms / epidemiology
  • Laryngeal Neoplasms / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Mouth Neoplasms / enzymology
  • Mouth Neoplasms / epidemiology
  • Mouth Neoplasms / genetics
  • Pharyngeal Neoplasms / enzymology
  • Pharyngeal Neoplasms / epidemiology
  • Pharyngeal Neoplasms / genetics
  • Polymorphism, Genetic
  • Risk Assessment
  • Smoke / analysis
  • Smoking / epidemiology

Substances

  • Smoke
  • Glucuronosyltransferase
  • UGT1A7 protein, human