Intl Journal of Cancer Lead exposure and brain cancer

[Guest guest]

By Crystal Phend, Staff Writer, MedPage Today

Reviewed by Rubeen K. Israni, M.D., Fellow, Renal-Electrolyte and

Hypertension Division, University of Pennsylvania School of Medicine

August 29, 2006

MedPage Today Action Points

* Explain to interested patients that exposure to lead at work may

increase their risk of brain cancer.

* Caution interested patients that the study looked at indirect

measures of lead exposure and that while some previous studies have

found an association between lead and cancer, others have not.

Review

ROCHESTER, N.Y., Aug. 29 -- There's not much chance of dying of brain

cancer, but occupational exposure to lead boosts that risk

significantly, according to epidemiologists who studied more than

300,000 workers.

The riskiest jobs were auto mechanics, heavy equipment mechanics, and

welders and flame cutters, according to the study published in the

Sept. 1 issue of the International Journal of Cancer. There was a

trend toward higher rates with greater probability and higher

intensity of lead exposure.

Individuals at the highest probability and intensity of exposure at

work were more than two times as likely to die from brain cancer as

nonexposed workers (hazard ratio 2.3; 95% confidence interval 1.3 to

4.2), reported Edwin van Wijngaarden, Ph.D., of the University of

Rochester, and Mustafa Dosemeci, Ph.D., of the National Cancer

Institute in Bethesda, Md.

Jobs with any potential lead exposure put workers at 1.5-fold higher

risk for death from brain cancer, even after adjusting for age and

gender (hazard ratio 1.5; 95% CI 5 0.9 to 2.3).

However, these findings " need to be interpreted cautiously due to the

consideration of brain cancer as one disease entity and the absence of

biological measures of lead exposure " in the study, wrote the

investigators.

The NCI-sponsored study analyzed job categories reported for 317,968

adults who participated in the National Longitudinal Mortality Study

from 1979 to 1989. The investigators compared the 119 brain cancer

deaths that occurred in this group over nine years of follow-up to

lead exposure based on a job exposure matrix that rated each

occupation for likelihood and intensity of exposure. Overall, 19% of

the cohort was deemed occupationally exposed to lead.

Low exposure probability jobs had a hazard ratio of 0.7 (95% CI 0.2 to

2.2) whereas the hazard ratio doubled to 1.4 (95% CI 0.8 to 2.5) for

medium exposure probability and jumped to 2.2 for high exposure

probability (95% CI 1.2-4.0).

Workers exposed to low intensity lead levels had a brain cancer

mortality hazard ratio of 1.2 compared to 1.9 for those in medium- to

high-exposure jobs (95% CI 0.7 to 2.1 and 1.0 to 3.4, respectively).

Most of the deaths in the medium- to high-intensity group occurred in

only three job categories, which were individually associated with

brain cancer mortality: automobile mechanics 2.30 hazard ratio (95% CI

0.56 to 9.56), heavy equipment mechanics 3.15 hazard ratio (95% CI

0.97 to 10.20) and welders and flame cutters 5.12 hazard ratio (95% CI

1.58-16.61).

The greatest potential for lead exposure has been in industrial

settings. However, " a five- to 10-fold decline in median and 75th

percentile of lead exposure in general industry has been reported

between 1979 and 1997, " Drs. van Wijngaarden and Dosemeci wrote.

Lead can cross the blood-brain barrier and accumulate in the body so

its effects may not be evident until long after occupational exposure

has ceased. Its carcinogenicity is thought to arise from inhibition of

DNA synthesis and repair, oxidative damage and interaction with

DNA-binding proteins and tumor suppressor proteins, the authors noted.

Previous studies have been inconclusive in demonstrating a link

between lead exposure and brain cancer with a meta-analysis concluding

" the evidence for excess brain cancer is weak, " the investigators

wrote. However, the number of deaths analyzed in Drs. van Wijngaarden

and Dosemeci's study was larger than in many previous studies and

" yielded risk estimates that were generally quite precise. "

They emphasized that the indirect measures of lead exposure used in

the study were " crude surrogates " for biological measures like bone

lead levels, which will be the focus of a pilot study by the group to

further characterize the lead-brain cancer association.

= -- = -- = --

International Journal of Cancer

Volume 119, Issue 5 , Pages 1136 - 1144

http://www3.inter

science.wiley.com/cgi-bin/abstract/112570700/ABSTRACT?SRETRY=0

Epidemiology

Brain cancer mortality and potential occupational exposure to lead:

Findings from the National Longitudinal Mortality Study, 1979-1989

Edwin van Wijngaarden 1 *, Mustafa Dosemeci 2

1Division of Epidemiology, Department of Community and Preventive

Medicine, University of Rochester School of Medicineand Dentistry,

Rochester, NY

2Occupational Epidemiology Branch, Division of Cancer Epidemiology and

Genetics, National Cancer Institute, Bethesda, MD

email: Edwin van Wijngaarden (edwin_van_wijngaarden@...)

*Correspondence to Edwin van Wijngaarden, Department of Community and

Preventive Medicine, University of Rochester School of Medicine and

Dentistry, 601 Elmwood Avenue, Box 644, Rochester, NY 14642, USA

Funded by:

Division of Cancer Epidemiology and Genetics

Intramural Research Program of the NIH

National Cancer Institute

Keywords

lead • occupation • brain neoplasms • cohort studies

Abstract

We evaluated the association between potential occupational lead

exposure and the risk of brain cancer mortality in the National

Longitudinal Mortality Study (NLMS), which is a prospective

census-based cohort study of mortality among the noninstitutionalized

United States population (1979-1989). The present study was limited to

individuals for whom occupation and industry were available (n =

317,968). Estimates of probability and intensity of lead exposure were

assigned using a job-exposure matrix (JEM). Risk estimates for the

impact of lead on brain cancer mortality were computed using

standardized mortality ratio (SMR) and proportional hazards and

Poisson regression techniques, adjusting for the effects of age,

gender and several other covariates. Brain cancer mortality rates were

greater among individuals in jobs potentially involving lead exposure

as compared to those unexposed (age- and gender-adjusted hazard ratio

(HR) = 1.5; 95% confidence interval (CI) = 0.9-2.3) with indications

of an exposure-response trend (probability: low HR = 0.7 (95% CI =

0.2-2.2), medium HR = 1.4 (95% CI = 0.8-2.5), high HR = 2.2 (95% CI =

1.2-4.0); intensity: low HR = 1.2 (95% CI = 0.7-2.1), medium/high HR =

1.9 (95% CI = 1.0-3.4)). Brain cancer risk was greatest among

individuals with the highest levels of probability and intensity (HR =

2.3; 95% CI = 1.3-4.2). These findings provide further support for an

association between occupational lead exposure and brain cancer

mortality, but need to be interpreted cautiously due to the

consideration of brain cancer as one disease entity and the absence of

biological measures of lead exposure. © 2006 Wiley-Liss, Inc.

Received: 11 November 2005; Accepted: 27 January 2006