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Glutathione S-Transferase GSTM3 and GSTP1 Genotypes and Larynx Cancer Risk¹

Unit of Cancer Epidemiology (Institut National de la Santé et de la Recherche Médicale U351), Institut Gustave-Roussy, 94805 Villejuif, France [N. J-M., S. B.]; Department of Industrial Hygiene and Toxicology, Finnish Institute of Occupational Health, 00250, Helsinki, Finland [A. V., H. W., A. H.]; Geneva Cancer Registry, 1205 Geneva, Switzerland [C. B.]; and Division of Clinical Pharmacology, University Hospital of Geneva, 1211 Geneva, Switzerland [P. D.]

Glutathione S-transferases (GSTs) are involved in detoxification of reactive metabolites of carcinogens and, therefore, could be potentially important in susceptibility to cancer. The associations between larynx cancer risk and GSTM3 and GSTP1 gene polymorphisms, either separately or in combination with GSTM1 and GSTT1 gene polymorphisms, were evaluated using peripheral blood DNA from 129 cancer patients and 172 controls, all regular smokers. The frequencies of GSTM3 AA, AB, and BB genotypes were 60.5%, 36.4%, and 3.1% in cases and 72.7%, 24.4%, and 2.9% in controls, respectively. The frequencies of GSTP1 AA, AG, and GG genotypes were 48.1%, 40.3%, and 11.6% in cases and 50.0%, 37.2%, and 12.8% in controls, respectively. Multivariate logistic regression analyses did not reveal any association between the GSTP1 (AG or GG) genotype and larynx cancer [odds ratio, 1.1; 95% confidence interval (CI), 0.7–2.0]. In contrast, a significant increase in risk was related to the GSTM3 (AB or BB) genotype (odds ratio, 2.0; 95% CI, 1.1–3.4). The combined GSTM3 (AB or BB) and GSTM1-null genotype conferred a 4-fold risk (95% CI, 1.6–10.1) of larynx cancer as compared with the combined GSTM3 AA and GSTM1-positive genotype. However, the effect of GSTM3 (AB or BB) genotype was similar among individuals with GSTM1-positive or GSTM1-null genotypes.

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