Laryngeal cancer risk in Caucasians is associated with alcohol and tobacco consumption but not modified by genetic polymorphisms in class I alcohol dehydrogenases ADH1B and ADH1C, and glutathione-S-transferases GSTM1 and GSTT1

Pharmacogenetics. 2003 Apr;13(4):225-30. doi: 10.1097/00008571-200304000-00007.

Abstract

Objective: Alcohol and tobacco consumption are recognized risk factors for upper aerodigestive tract tumours, however individual susceptibility to these environmental factors varies. As part of the Rhein-Neckar Larynx-case-control study, this study investigated the potential risk-modifying effect of genetic polymorphisms in enzymes involved in ethanol and tobacco carcinogen metabolism for laryngeal cancer in Germany.

Methods: Two hundred and forty-five cases and 251 population-based controls, matched by age and gender, were genotyped for genetic polymorphisms in ADH1B, ADH1C, GSTM1 and GSTT1, using genomic DNA isolated from peripheral lymphocytes and employing PCR and PCR/restriction fragment length polymorphism-based methods.

Results: Neither the putative risk genotypes ADH1B*2/*1 (OR 0.86, 95% confidence interval (CI): 0.41-1.82) or ADH1C*1/*1 (OR 1.06, CI 0.7-1.62) nor GSTM1 null (OR 0.94, CI 0.62-1.42) or GSTT1 null (OR 1.34, CI 0.74-2.42) were associated with an overall increased risk for laryngeal cancer. Stratified analyses were carried out to determine the gene-environment interaction in relation to laryngeal cancer risk. However, ADH1B or ADH1C genotypes did not markedly modify the risk observed after stratification by alcohol consumption, and stratification by cumulative smoking exposure (in packyears) did not show an association of GSTM1 or GSTT1 genotype with laryngeal carcinoma either.

Conclusion: The lack of risk modification by the studied genotypes emphasizes the importance of environmental exposure to tobacco smoke and alcohol as major risk factors for laryngeal cancer in the German study population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Dehydrogenase / genetics*
  • Alcohol Drinking / adverse effects*
  • DNA / blood
  • DNA / genetics
  • DNA / isolation & purification
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / genetics
  • DNA, Neoplasm / isolation & purification
  • European Continental Ancestry Group / genetics*
  • Genotype
  • Germany
  • Glutathione Transferase / genetics*
  • Humans
  • Laryngeal Neoplasms / enzymology
  • Laryngeal Neoplasms / epidemiology*
  • Laryngeal Neoplasms / genetics
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Polymorphism, Restriction Fragment Length
  • Smoking / adverse effects*

Substances

  • DNA, Neoplasm
  • DNA
  • ADH1B protein, human
  • ADH1C protein, human
  • Alcohol Dehydrogenase
  • glutathione S-transferase T1
  • Glutathione Transferase
  • glutathione S-transferase M1