Carcinogenesis Advance Access originally published online on June 19, 2008
Carcinogenesis 2008 29(8):1567-1571; doi:10.1093/carcin/bgn153
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Renal cell carcinoma, occupational pesticide exposure and modification by glutathione S-transferase polymorphisms
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852, USA
1 International Agency for Research on Cancer, Lyon 69008, France
2 Institute of Carcinogenesis, Cancer Research Centre, Moscow 115478, Russia
3 Department of Preventive Medicine, Faculty of Medicine, Palacky University, Olomouc 77515, Czech Republic
4 Institute of Hygiene and Epidemiology, First Faculty of Medicine, Charles University, Prague 12800, Czech Republic
5 Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute, Brno 65653, Czech Republic
6 Department of Epidemiology, Institute of Occupational Medicine, Lodz 90950, Poland
7 Institute of Public Health, Bucharest 050643, Romania
8 Core Genotyping Facility at the Advanced Technology Center of the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20852, USA
9 Department of Chemical Hazards, Nofer Institute of Occupational Medicine, Lodz 91311, Poland
* To whom correspondence should be addressed. Tel: +301 451 7393; Fax: +301 402 1819; Email: karamis{at}mail.nih.gov
This study investigated associations between occupational pesticide exposure and renal cell carcinoma (RCC) risk. To follow-up on a previous report by Buzio et al., we also considered whether this association could be modified by glutathione S-transferase M1 and T1 (GSTM1 and GSTT1) genotypes. About 1097 RCC cases and 1476 controls from Central and Eastern Europe were interviewed to collect data on lifetime occupational histories. Occupational information for jobs held for at least 12 months duration was coded for pesticide exposures and assessed for frequency and intensity of exposure. GSTM1 and GSTT1 gene deletions were analyzed using TaqMan® assays. A significant increase in RCC risk was observed among subjects ever exposed to pesticides [odds ratio (OR): 1.60; 95% confidence interval (CI): 1.00–2.55]. After stratification by genotypes, increased risk was observed among exposed subjects with at least one GSTM1 active allele (OR: 4.00; 95% CI: 1.55–10.33) but not among exposed subjects with two GSTM1 inactive alleles compared with unexposed subjects with two inactive alleles (P-interaction: 0.04). Risk was highest among exposed subjects with both GSTM1 and GSTT1 active genotypes (OR: 6.47; 95% CI: 1.82–23.00; P-interaction: 0.02) compared with unexposed subjects with at least one GSTM1 or T1 inactive genotype. In the largest RCC case–control study with genotype information conducted to date, we observed that risk associated with pesticide exposure was exclusive to individuals with active GSTM1/T1 genotypes. These findings further support the hypothesis that glutathione S-transferase polymorphisms can modify RCC risk associated with occupational pesticide exposure.
Abbreviations: CI, confidence interval; GST, glutathione S-transferase; OR, odds ratio; RCC, renal cell carcinoma
Received April 12, 2008; revised June 5, 2008; accepted June 14, 2008.