Lead, Genetic Susceptibility, and Risk of Adult Brain Tumors
- Preetha Rajaraman1,
- Patricia A. Stewart1,
- Jonathan M. Samet4,
- Brian S. Schwartz4,
- Martha S. Linet1,
- Shelia Hoar Zahm1,
- Nathaniel Rothman1,
- Meredith Yeager2,
- Howard A. Fine3,
- Peter M. Black5,
- Jay Loeffler6,
- William R. Shapiro7,
- Robert G. Selker8 and
- Peter D. Inskip1
- 1Division of Cancer Epidemiology and Genetics, 2Core Genotyping Facility, and 3Neuro-Oncology Branch, National Cancer Institute, NIH, Department of Health and Human Services, Bethesda, Maryland; 4Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland; 5Brigham and Women's Hospital, Boston, MA; 6Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts; 7Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona; and 8Western Pennsylvania Hospital, Pittsburgh, Pennsylvania
- Requests for reprints:
Preetha Rajaraman, Radiation Epidemiology Branch, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard, EPS Room 7085, Bethesda, MD 20892-7238. Phone: 301-496-8847; Fax: 301-402-0207. E-mail: rajarama{at}mail.nih.gov
Abstract
Background: Although few etiologic factors for brain tumors have been identified, limited data suggest that lead may increase the risk of brain tumors, particularly meningioma. The ALAD G177C polymorphism affects the toxicokinetics of lead and may confer genetic susceptibility to adverse effects of lead exposure.
Methods: We examined occupational exposure to lead and risk of brain tumors in a multisite, hospital-based, case-control study of 489 patients with glioma, 197 with meningioma, and 799 non-cancer controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to hospital. ALAD genotype was assessed by a Taqman assay for 355 glioma patients, 151 meningioma patients, and 505 controls. Exposure to lead was estimated using a rigorous questionnaire-based exposure assessment strategy incorporating lead measurement and other occupational data abstracted from published articles and reports.
Results: Increased risk of meningioma with occupational lead exposure (estimated by odds ratios and 95% confidence intervals) was most apparent in individuals with the ALAD2 variant allele, for whom risk increased from 1.1 (0.3-4.5) to 5.6 (0.7-45.5) and 12.8 (1.4-120.8) for estimated cumulative lead exposures of 1 to 49 μg/m3-y, 50 to 99 μg/m3-y, and ≥100 μg/m3-y, respectively, compared with unexposed individuals (two-sided P trend = 0.06). This relationship became stronger after excluding occupational lead exposures characterized by a low confidence level or occurring in the 10 years before meningioma diagnosis. Occupational lead exposure was not associated with glioma risk.
Conclusions: Although our results indicate that lead may be implicated in meningioma risk in genetically susceptible individuals, these results need to be interpreted with caution given the small numbers of exposed cases with a variant genotype. (Cancer Epidemiol Biomarkers Prev 2006;15(12):2514–20)
Footnotes
-
Grant support: National Cancer Institute, NIH, Department of Health and Human Services.
-
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
- Accepted September 25, 2006.
- Received June 13, 2006.
- Revision received September 14, 2006.
