Glutathione S-transferase GSTM1, GSTM3, GSTP1 and GSTT1 genotypes and the risk of smoking-related oral and pharyngeal cancers

Int J Cancer. 1999 Mar 31;81(1):44-8. doi: 10.1002/(sici)1097-0215(19990331)81:1<44::aid-ijc9>3.0.co;2-a.

Abstract

Several polymorphic glutathione S-transferase enzymes are involved in the detoxification of active metabolites of many potential carcinogens from tobacco smoke and may therefore be important in modulating susceptibility to smoking-related cancers. As part of a hospital-based case-control study performed in France among Caucasian smokers, we studied GSTM1, GSTM3, GSTP1 and GSTT1 gene polymorphisms in 121 patients with oral cavity and pharyngeal cancers and 172 hospital controls using peripheral blood DNA. An increase in risk was found among carriers of the GSTP1 (AG or GG) genotype (OR 1.6, 95% CI 1.0-2.8, p = 0.07) or the GSTT1 null genotype (OR 2.0, 95% CI 1.0-4.0, p = 0.05). The effect of these at-risk genotypes was most marked in subjects with a history of more than 30 years of smoking, among whom the respective ORs were 2.0 (95% CI 1.0-3.9) and 3.3 (95% CI 1.3-8.1), though the interaction tests between these genotypes and duration of smoking were not significant. In contrast, neither the GSTM1 null genotype nor the GSTM3 AA genotype was associated with oropharyngeal cancer risk (OR 0.9, 95% CI 0.5-1.5 and OR = 1.3, 95% CI 0.7-2.3, respectively). Our results thus suggest that GSTP1 and GSTT1 gene polymorphisms modulate susceptibility to smoking-related cancers of the oral cavity and pharynx.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Genotype
  • Glutathione Transferase / genetics*
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / enzymology*
  • Mouth Neoplasms / etiology
  • Mouth Neoplasms / genetics
  • Pharyngeal Neoplasms / enzymology*
  • Pharyngeal Neoplasms / etiology
  • Pharyngeal Neoplasms / genetics
  • Polymorphism, Genetic*
  • Risk Factors
  • Smoking / adverse effects*
  • Smoking / genetics

Substances

  • Glutathione Transferase