Case-control study of oral and oropharyngeal cancer in whites and genetic variation in eight metabolic enzymes

Head Neck. 2008 Sep;30(9):1139-47. doi: 10.1002/hed.20867.

Abstract

Background: Genetic variation in xenobiotic metabolizing enzymes may explain differing susceptibilities to the cancer causing effects of tobacco and alcohol.

Methods: We compared 203 oral squamous cell carcinoma cases and 416 controls for single nucleotide polymorphisms (SNPs) in 8 genes (CYP1A1, CYP2E1, MPO, mEH, GSTM1, GSTT1, GSTP1, and NAT2). Except for NAT2, genotype frequencies were similar in the 2 groups. We classified subjects as fast or slow NAT2 acetylators genotyping 13 NAT2 SNPs.

Results: Fast acetylators were overrepresented in cases (53.7%) compared with controls (43.9%; odds ratio (OR) 1.55, 95% confidence interval (CI) 1.08-2.20; p value = .03). Gene-gene interaction testing suggested several cancer-NAT2 associations, with association strongest among persons without a CYP1A1 variant (*2C or *4) allele (OR 1.77, 95% CI 1.20-2.60, p value = .03) or with a variant MPO (463A) allele (OR 2.38, 95% CI 1.34-4.21, p value = .05).

Conclusion: These results implicate fast NAT2 acetylation as a risk factor for oral cancer.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism*
  • Carcinoma, Squamous Cell / enzymology*
  • Carcinoma, Squamous Cell / ethnology
  • Carcinoma, Squamous Cell / genetics*
  • Case-Control Studies
  • Chi-Square Distribution
  • Cytochrome P-450 CYP1A1 / genetics
  • Cytochrome P-450 CYP1A1 / metabolism
  • Cytochrome P-450 CYP2E1 / genetics
  • Cytochrome P-450 CYP2E1 / metabolism
  • European Continental Ancestry Group / genetics*
  • Female
  • Gene Expression Regulation, Enzymologic / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Glutathione Transferase / genetics
  • Glutathione Transferase / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / ethnology
  • Mouth Neoplasms / genetics*
  • Odds Ratio
  • Oropharyngeal Neoplasms / enzymology*
  • Oropharyngeal Neoplasms / ethnology
  • Oropharyngeal Neoplasms / genetics*
  • Polymorphism, Single Nucleotide
  • Reference Values
  • Risk Assessment
  • Survival Analysis

Substances

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