Lead, genetic susceptibility, and risk of adult brain tumors.
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 microg/m3-y, 50 to 99 microg/m3-y, and >or=100 microg/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.
Rajaraman
Preetha
P
Division of Cancer Epidemiology Branch, National Cancer Institute, NIH, Department of Health and Human Services, 6120 Executive Boulevard, EPS Room 7085, Bethesda, MD 20892-7238, USA. rajarama@mail.nih.gov
Stewart
Patricia A
PA
Samet
Jonathan M
JM
Schwartz
Brian S
BS
Linet
Martha S
MS
Zahm
Shelia Hoar
SH
Rothman
Nathaniel
N
Yeager
Meredith
M
Fine
Howard A
HA
Black
Peter M
PM
Loeffler
Jay
J
Shapiro
William R
WR
Selker
Robert G
RG
Inskip
Peter D
PD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001130:Arizona; D001932:Brain Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005910:Glioma / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D007854:Lead / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008404:Massachusetts / Q000453:epidemiology; D008579:Meningioma / Q000139:chemically induced / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D016273:Occupational Exposure / Q000009:adverse effects*; D010414:Pennsylvania / Q000453:epidemiology
D007854:Lead