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Polymorphisms in DNA repair genes and susceptibility to primary intracranial brain gliomas.

Butler M; Ruder A; Carreon T; Waters M; Yeager M; Welch R; Chanock S; Schulte P
Neuro-Oncology 2005 Jul; 7(3):287
Enzymes in base excision (BER), nucleotide excision (NER), double strand break/recombination (DSB/RR), mismatch (MMR), and direct-damage DNA repair pathways are important in the repair of diverse types of DNA damage. Polymorphisms in many of the genes encoding these enzymes have been identified as risk factors for environmentally and occupationally caused cancers. We evaluated the associations of polymorphisms in BER (ADPRTV762A, APEXD148E, MUTYH Ex1+8A>C>G/T, OGG1S326C, POLB IVS11-235A>G, XRCC1 R399Q, R280H, R194W, LIG1Ex2-24C>T, PCNA IVS1-124C>T), NER (ERCC2 D312N, K751Q, ERCC4 R415Q, ERCC5 H1104D, RAD23B A249V, LIG1 Ex2-24C>T, PCNA IVS1-124C>T), DSB/RR (NBS1 Q185E, RAD52 Y41stop, XRCC2 R186H, XRCC3 T241M, XRCC4 N298S), MMR (MLH1 I219V, MSH2 G322D), and direct damage repair (MGMTI143V, R178K, L84F) as risk factors for primary intracranial gliomas in the Upper Midwest Health Study, a population-based case-control study including rural residents of four states with high glioma incidence. Glioma cases (N=798) were identified from hospitals, private physicians and registries. Control participants (N=1175) were stratified samples of licensed drivers and HCFA enrollees. Questionnaires elicited occupational and environmental exposures. DNA was obtained from 451 controls with no self-reported cancer and from 316 cases. TaqMan and MGB Eclipse methodology were used to characterize genotypes. In unadjusted analyses, a polymorphism in ADPRT (V/V 67% of controls, 75% of cases, odds ratio [OR] 1.48 95% confidence interval [CI] 1.07-2.04) had a statistically significant association with glioma of borderline statistical significance: (1) RAD23B A/V + V/V, 32% of controls, 38% of cases, OR 1.32, CI 0.97-1.78; (2) ERCC5 H/H, 61% of controls, 68% of cases, OR 1.33, CI 0.98-1.78; and (3) XRCC4 N/N 74% of controls, 80% of cases, OR 1.37, CI 0.97-1.94. For each DNA repair pathway, multivariate logistic analyses included all polymorphisms in the pathway plus ever/never living on a farm and ever/never smoking, as surrogates for occupational and environmental exposure. Adjusting for these factors did not change odds ratios substantially. Our results should be confirmed in additional glioma case-control studies. Future analyses of our data will include assessing risk of DNA repair polymorphisms under specific exposure conditions, such as exposures to pesticides, solvents, and UV light.
DNA-damage; Genes; Brain-disorders; Brain-damage; Cancer; Risk-factors; Case-studies; Questionnaires; Occupational-exposure; Environmental-exposure
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Abstract; Conference/Symposia Proceedings
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Research Tools and Approaches: Exposure Assessment Methods
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Page last reviewed: January 28, 2022
Content source: National Institute for Occupational Safety and Health Education and Information Division