Glutathione S-transferase M1, T1, and P1 polymorphisms as risk factors forrenal cell carcinoma: A case-control study

Renal cell carcinoma (RCC) has known environmental risk factors, notably sm oking, and enzymes that biotransform carcinogens hare high levels of activi ty in the kidney. However, a possible role of polymorphisms in these enzyme s in RCC etiology has received little study. We investigated glutathione S- transferase (GST) polymorphisms in a population-based case-control study of RCC. Subjects completed a structured interview, and DNA was isolated from pathological material or buccal cells for 130 cases, and from blood for 505 controls. Genotypes for GSTM1 and GSTT1 were determined by multiplex PCR, and for GSTP1 by oligonucleotide ligation assay. The frequency of GSTM1 nul l genotype was 50.0% in cases and 50.5% in controls, with an adjusted odds ratio (OR) of 1.0 [95% confidence interval (CI), 0.6-1.6]. For GSTP1, the f requencies of genotypes AA, AG, and GG representing the Ile(104)Val variant were: cases, 44.6%, 43.1%, and 12.3%; controls, 43.4%, 44.0% and12.6%; OR for AG and GG, 1.0 (95% CI, 0.6-1.6). An excess of the GSTT1 null genotype was observed in cases compared with controls, 28.6% versus 18.5% (OR, 1.9; 95% CI, 1.1-3.4). The association with GSTT1 was present among both smokers and nonsmokers, but was modified by body mass index, a recognized risk fac tor for RCC; among subjects in the lowest tertile of body mass index, the O R for GSTT1 null was 4.8 (95% CI, 1.8-13.0). The association between GSTT1 null and increased RCC risk in this population-based study suggests that ac tivity of the GSTT1 enzyme protects against RCC. This contrasts with a rece nt report of reduced risk of RCC associated with GSTT1 null in a cohort of trichloroethene-exposed workers and suggests that specific chemical exposur es alter the effect of GSTT1 on cancer risk.