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Polymorphisms in GSTM1, GSTT1, GSTP1, and NAT2 and susceptibility to primary intracranial brain gliomas.

Butler-MA; Ruder-AM; Daly-AK; Waters-MA; Carreon-T; Schulte-PA
Proceedings of the American Association for Cancer Research (AACR) 94th Annual Meeting, July 11-14, 2003, Washington, DC. 2nd edition. Philadelphia, PA: American Association for Cancer Research, 2003 Jul; 44:106
Enzymes encoded by GSTM1, GSTT1, GSTP1, and NAT2 are important in the biotransformation of a variety of carcinogens and polymorphisms in these genes have been identified as risk factors for numerous environmentally and occupationally induced cancers. In order to evaluate GSTM1, GSTT1, GSTP1, and NAT2 polymorphisms as risk factors in primary intracranial gliomas and explore their interactions with exposure, we determined their prevalence in participants in the Upper Midwest Health Study. This population-based case-control study was designed to identify risk factors for gliomas in rural residents in four upper midwestern states with high glioma incidence. Glioma cases (n=799) were identified from hospitals, private medical practices, and cancer registries. Controls (n=1176) were stratified samples of licensed drivers and HCFA enrollees. Questionnaires were administered to participants to identify occupational and environmental exposures. Blood was obtained from 325 case and 579 control participants. DNA was prepared from whole blood using solvent extraction procedures, and RFLP/PCR and gel electrophoresis procedures were used to characterize polymorphisms. We characterized GSTM1 (wild type and *0/*0), GSTT1 (wild type and *0/*0), GSTP1 *A, *B, *C, and *D, and NAT2 *4, *5A, *5B, *5C, *5E, *6, *7, *14, *12A, *12B, and *12C alleles. There were no statistically significant associations between polymorphisms and increased risk of glioma: GSTM1 *0/*0, present in 50.7% of controls and 50.6% of cases (odds ratio (OR) 1.00, 95% confidence interval (CI) 0.76-1.31); GSTT1 *0/*0, present in 14.6% of controls and 17.2% of cases (OR 1.22, CI 0.84-1.77); GSTP1 *B and *C 105val/105val present in 12.9% of controls and 11.5% of cases (OR 0.88, CI 0.58-1.34); NAT2 rapid acetylation status observed in 42.7% of controls and 48.1% of cases (OR 1.25, 95% CI 0.95-1.64). In addition, there were no statistically significant associations between specific polymorphisms and histopathologic subtypes. To determine if the polymorphisms were risk factors only under specific exposure conditions, participants were stratified by smoking status: ever (162 cases, 330 controls), never (163 cases, 249 controls); and by living on farm status: never (141 cases, 199 controls), ever but pesticides never used (71 cases, 130 controls), and ever and pesticides ever used (113 cases, 250 controls). Unadjusted odds ratio for polymorphism frequencies did not differ significantly between cases and controls in any of the subgroups. A multivariate logistic regression including all four polymorphisms plus farm status found a borderline increased risk for glioma associated with NAT2 rapid acetylator and a non-statistically significant increased risk associated with GSTT1 *0/*0. Future analyses will include additional occupational exposures.
Brain-tumors; Brain-matter; Brain-function; Brain-disorders; Farmers; Histology; Central-nervous-system; Neurotoxicity; Exposure-levels; Exposure-limits; Sex-factors; Hormones; Hormone-activity; Endocrine-system; Endocrine-function; Endocrine-system-disorders; Pesticides; Pesticide-residues; Pesticides-and-agricultural-chemicals; Demographic-characteristics; Agricultural-workers; Agricultural-chemicals
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Proceedings of the American Association for Cancer Research (AACR) 94th Annual Meeting, July 11-14, 2003, Washington, DC. 2nd edition