Lead Exposure, Polymorphisms in Genes Related to Oxidative Stress, and Risk of Adult Brain Tumors

Cancer Epidemiology Biomarkers and Prevention - Tập 18 Số 6 - Trang 1841-1848 - 2009
Parveen Bhatti1,2, Patricia A. Stewart3, Amy Hutchinson4, Nathaniel Rothman1, Martha S. Linet1, Peter D. Inskip1, Preetha Rajaraman1
11Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health ad Human Services, Bethesda, Maryland;
22Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington;
33Stewart Exposure Assessments, LLC, Arlington, Virginia; and
44Core Genotyping Facility, Division of Cancer Epidemiology and Genetics, Advanced Technology Program, Science Applications International Corporation-Frederick, Inc., National Cancer Institute, Frederick, Maryland

Tóm tắt

Abstract There is some evidence that oxidative stress plays a role in lead-induced toxicity. Mechanisms for dealing with oxidative stress may be of particular relevance in the brain given the high rate of oxygen metabolism. Using a hospital-based case-control study, we investigated the role of oxidative stress in the potential carcinogenicity of lead through examination of effect modification of the association between occupational lead exposure and brain tumors by single nucleotide polymorphisms in genes with functions related to oxidative stress. The study included 362 patients with glioma (176 of which had glioblastoma multiforme), 134 patients with meningioma, and 494 controls. Lead exposure was estimated by expert review of detailed job history data for each participant. We evaluated effect modification with 142 single nucleotide polymorphisms using likelihood ratio tests that compared nested unconditional logistic regression models that did and did not include a cross-product term for cumulative lead exposure and genotype. When the analyses were restricted to cases with glioblastoma multiforme, RAC2 rs2239774 and two highly correlated GPX1 polymorphisms (rs1050450 and rs18006688) were found to significantly modify the association with lead exposure (P ≤ 0.05) after adjustment for multiple comparisons. Furthermore, the same GPX1 polymorphisms and XDH rs7574920 were found to significantly modify the association between cumulative lead exposure and meningioma. Although the results of this study provide some evidence that lead may cause glioblastoma multiforme and meningioma through mechanisms related to oxidative damage, the results must be confirmed in other populations. (Cancer Epidemiol Biomarkers Prev 2009;18(6):1841–8)

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Tài liệu tham khảo

IARC. Inorganic and organic lead compounds. Lyon: IARC; 2004.

Ahamed M, Siddiqui MK. Low level lead exposure and oxidative stress: current opinions. Clin Chim Acta 2007;383:57–64.

Silbergeld EK. Facilitative mechanisms of lead as a carcinogen. Mutat Res 2003;533:121–33.

Halliwell B. Oxidative stress and neurodegeneration: where are we now? J Neurochem 2006;97:1634–58.

Cocco P, Dosemeci M, Heineman EF. Brain cancer and occupational exposure to lead. J Occup Environ Med 1998;40:937–42.

Cocco P, Heineman EF, Dosemeci M. Occupational risk factors for cancer of the central nervous system (CNS) among US women. Am J Ind Med 1999;36:70–4.

Hu J, Little J, Xu T, et al. Risk factors for meningioma in adults: a case-control study in northeast China. Int J Cancer 1999;83:299–304.

Hu YJ, Diamond AM. Role of glutathione peroxidase 1 in breast cancer: loss of heterozygosity and allelic differences in the response to selenium. Cancer Res 2003;63:3347–51.

Navas-Acien A, Pollan M, Gustavsson P, Plato N. Occupation, exposure to chemicals and risk of gliomas and meningiomas in Sweden. Am J Ind Med 2002;42:214–27.

van Wijngaarden E, Dosemeci M. Brain cancer mortality and potential occupational exposure to lead: findings from the National Longitudinal Mortality Study, 1979-1989. Int J Cancer 2006;119:1136–44.

Wesseling C, Pukkala E, Neuvonen K, Kauppinen T, Boffetta P, Partanen T. Cancer of the brain and nervous system and occupational exposures in Finnish women. J Occup Environ Med 2002;44:663–8.

Wong O, Harris F. Cancer mortality study of employees at lead battery plants and lead smelters, 1947-1995. Am J Ind Med 2000;38:255–70.

Anttila A, Heikkila P, Nykyri E, et al. Risk of nervous system cancer among workers exposed to lead. J Occup Environ Med 1996;38:131–6.

Gerhardsson L, Hagmar L, Rylander L, Skerfving S. Mortality and cancer incidence among secondary lead smelter workers. Occup Environ Med 1995;52:667–72.

Inskip PD, Tarone RE, Hatch EE, et al. Cellular-telephone use and brain tumors. N Engl J Med 2001;344:79–86.

Rajaraman P, Stewart PA, Samet JM, et al. Lead, genetic susceptibility, and risk of adult brain tumors. Cancer Epidemiol Biomarkers Prev 2006;15:2514–20.

Rajaraman P, Hutchinson A, Rothman N, et al. Oxidative response gene polymorphisms and risk of adult brain tumors. Neuro-oncol 2008;10:709–15.

Stewart PA, Stewart WF, Heineman EF, Dosemeci M, Linet M, Inskip PD. A novel approach to data collection in a case-control study of cancer and occupational exposures. Int J Epidemiol 1996;25:744–52.

Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 1995;57:289–300.

Barrett JC, Fry B, Maller J, Daly MJ. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005;21:263–5.

Hu J, Johnson KC, Mao Y, et al. Risk factors for glioma in adults: a case-control study in northeast China. Cancer Detect Prev 1998;22:100–8.

Idbaih A, Paris S, Boisselier B, et al. Mutational analysis of Rac2 in gliomas. J Neurooncol 2008;87:365–6.

Hwang SL, Lieu AS, Chang JH, et al. Rac2 expression and mutation in human brain tumors. Acta Neurochir (Wien) 2005;147:551–4; discussion 4.

Sun D, Xu D, Zhang B. Rac signaling in tumorigenesis and as target for anticancer drug development. Drug Resist Updat 2006;9:274–87.

Lei XG, Cheng WH, McClung JP. Metabolic regulation and function of glutathione peroxidase-1. Annu Rev Nutr 2007;27:41–61.

Ahamed M, Siddiqui MK. Environmental lead toxicity and nutritional factors. Clin Nutr 2007;26:400–8.

Nishino T, Okamoto K, Eger BT, Pai EF, Nishino T. Mammalian xanthine oxidoreductase—mechanism of transition from xanthine dehydrogenase to xanthine oxidase. FEBS J 2008;275:3278–89.

Ariza ME, Bijur GN, Williams MV. Lead and mercury mutagenesis: role of H2O2, superoxide dismutase, and xanthine oxidase. Environ Mol Mutagen 1998;31:352–61.

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Thông tin xuất bản

Cancer Epidemiology Biomarkers and Prevention

Tập 18 Số 6

1841-1848

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