CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms, smoking, consumption of alcohol and fruit and vegetables and risk of head and neck cancer

J Cancer Res Clin Oncol. 2008 Jan;134(1):93-100. doi: 10.1007/s00432-007-0254-5. Epub 2007 Jul 5.


Purpose: As risk-modifiers of alcohol and tobacco effects, metabolic genes polymorphisms were investigated as susceptibility candidates for squamous cell carcinoma of the head and neck (SCCHN).

Methods: A total of 210 cases and 245 hospital controls, age and gender matched, were genotyped for CYP1A1, CYP2E1, GSTM1, GSTT1, EPHX1 exons 3 and 4, and NAT2 polymorphisms. A measurement of the biological interaction among two risk factors was estimated by the attributable proportion (AP) due to interaction and its 95% confidence interval (CI).

Results: SCCHN risk was associated with high-levels of alcohol intake [OR = 3.50 (95%CI: 1.93-6.35) and OR = 6.47 (95%CI: 2.92-14.35) for 19-30 g/day and >30 g/day, respectively], cigarette smoking [OR = 3.47 (95%CI: 1.88-6.41) and OR = 7.65 (95%CI: 4.20-13.90) for 1-25 and >25 pack-years of smoking, respectively] and low-fruit and vegetables consumption (OR = 2.45; 95%CI: 1.53-3.92). No differences were observed for the genotypes or haplotypes distributions among cases and controls, and no biological interaction emerged from gene-gene and gene-environment interaction analyses. An attributable proportion (AP) due to biological interaction of 0.65 (95%CI: 0.40-0.90) was detected for heavy drinkers with a low intake of fruit and vegetables, and an AP of 0.40 (95%CI: 0.10-0.72) resulted forever smokers with low fruit and vegetables consumption.

Conclusions: Even in presence of high alcohol consumption or cigarette smoking, a high intake of fruit and vegetables might prevent the development of around one quarter of SCCHN cases. The lack of interaction between the studied polymorphisms and the environmental exposures suggests that chronic consumption of tobacco and alcohol overwhelm enzyme defences, irrespective of genotype.

Publication types

  • Comparative Study

MeSH terms

  • Alcohol Drinking*
  • Arylamine N-Acetyltransferase / genetics
  • Carcinoma, Squamous Cell / epidemiology
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / prevention & control
  • Case-Control Studies
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP2E1 / genetics
  • Diet*
  • Enzymes / genetics*
  • Epoxide Hydrolases / genetics
  • Exons / genetics
  • Female
  • Follow-Up Studies
  • Fruit
  • Genetic Predisposition to Disease
  • Genotype
  • Glutathione Transferase / genetics
  • Head and Neck Neoplasms / epidemiology
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / prevention & control
  • Humans
  • Italy / epidemiology
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Risk Management
  • Smoking*
  • Surveys and Questionnaires
  • Vegetables


  • Enzymes
  • Cytochrome P-450 CYP2E1
  • Cytochrome P-450 CYP1A1
  • Arylamine N-Acetyltransferase
  • NAT2 protein, human
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1
  • Epoxide Hydrolases
  • EPHX1 protein, human