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Extramural Papers of the Month

By Jerry Phelps
November 2007

Age-Related Cognitive Decline and Lead Exposure

New research by NIEHS-supported investigators suggests that the "normal" cognitive decline experienced as we age may be related to our recent and life-time exposure to lead. In three separate independent epidemiologic studies, bone lead content was associated with poorer measures of cognitive function.

One study included 1,109 former U.S. employees of a tetraethyl lead manufacturing facility. Tetraethyl lead was used in gasoline in the U.S. from the 1920's to the 1970's. Another study was based on 803 current and former workers in a Korean inorganic lead industrial setting. Participants in the third study were 1,140 Baltimore residents, aged 50-70, with environmental lead exposure.

Bone lead was measured using X-ray fluorescence of the tibia. The researchers noted a persistent and consistent association of poorer cognitive function with higher tibia lead levels in all three studies. MRI brain scans in the U.S. worker cohort also showed lower brain volumes in people with high tibia lead. The research also indicates that the greater the bone lead content, the sooner the cognitive decline starts.

Added to the knowledge that exposure to lead lowers the peak IQ a person reaches, these studies show that lead exposure is a life-long issue. The authors also point out that the current occupational safety standards for lead workers are inadequate to protect them.

Citation: Stewart WF, Schwartz BS Exit NIEHS . 2007. Effects of lead on the adult brain: a 15-year exploration. Am J Ind Med 50(10):729-739.

Have Particulate Air Pollution Regulations Affected Mortality Risks?

Particulate air pollution has been linked to cardiovascular mortality and has resulted in increasingly stringent air pollution regulations. Not surprisingly, policy makers and industry officials are eager to know if these tougher regulations are having the desired effect-protecting public health. NIEHS-supported researchers conducted a statistical analysis of particulate matter air pollution and mortality trends from 1987 through 2000, a period during which the EPA set new air quality standards. They found a strong indication that exposures to particulate matter continue to be associated with increased mortality.

Annual averages of ambient air concentrations of particulate matter less than 10 microns and less than 2.5 microns in diameter declined nationwide during the study period. The analysis showed a small decline in the short-term effects of particulate matter on mortality, and most of this decline occurred in counties in the eastern United States.

Called "accountability research," this type of analysis is relatively new and "is viewed as an emerging component of responsible governmental policy intervention and environmental health tracking and research." While this study does not provide conclusive evidence of health benefits from more stringent regulation, it does have the potential to provide necessary data for regulatory agencies so that informed decisions can be made.

Citation: Dominici F, Peng RD, Zeger SL, White RH, Samet JM Exit NIEHS . Particulate air pollution and mortality in the United States: did the risks change from 1987 to 2000? Am J Epidemiol. 2007 Oct 15;166(8):880-8.

Statin Drugs Maintain Lung Function in the Elderly

Cholesterol-lowering statin drugs have become increasingly popular since their introduction in the 1990s, with about 12 million current prescriptions in the U.S. for patients with cardiovascular disease risk. Statins have also been shown to have anti-inflammatory and anti-oxidant properties. NIEHS-supported investigators hypothesized that the drugs may have a beneficial effect on maintaining lung function in elderly subjects by reducing inflammation and oxidative stress.

The researchers performed their study with a population of men, average age greater than 70, enrolled in the Normative Aging Study. Lung function tests had been performed on these men 2-4 times between 1995 and 2005. At each visit, the subjects were questioned about their use of statins as well as their smoking history. In summary, statin use reduced the yearly decline in "normal" lung function by about 50 per cent. Statin use significantly reduced the deficits in both forced expiratory volume and forced vital capacity in smokers and non-smokers.

This study is the first to show the benefits of statin use for maintaining lung function in elderly subjects regardless of smoking history. If confirmed in a randomized clinical trial, these results point to a possible treatment for impaired lung function, especially in patients with a history of smoking.

Citation: Alexeeff SE, Litonjua AA, Sparrow D, Vokonas PS, Schwartz J. Exit NIEHS 2007. Statin use reduces decline in lung function: VA Normative Aging Study. Am J Respir Crit Care Med 176(8):742-747.

Polymorphisms in Nucleotide Excision Repair Genes and Breast Cancer Risk

Genes responsible for nucleotide excision repair, the process that removes bulky DNA adducts, are thought to be cancer susceptibility genes. In a collaborative study, NIEHS grantees at the Columbia University Mailman School of Public Health and the University of North Carolina School of Public Health investigated whether single nucleotide polymorphisms of nucleotide excision repair genes are associated with changes in the risk for breast cancer.

The researchers analyzed a population-based breast cancer case-control study on Long Island, New York. They examined polymorphisms in four nucleotide excision repair genes in over one thousand breast cancer cases and a similar number of control subjects. Study subjects with at least one variant allele in the gene XPD were found to have a 25 per cent greater risk for breast cancer. The risk was almost two times as high in subjects with detectable DNA adducts. Although the increases in risk are modest, they were statistically significant.

In summary, this study suggests that certain polymorphisms in nucleotide excision repair genes increase the risk of breast cancer in women. The risk is increased when DNA adducts are present. These results may improve the identification of high-risk individuals and preventable environmental risk factors for breast cancer.

Citation: Crew KD, Gammon MD, Terry MB, Zhang FF, Zablotska LB, Agrawal M, Shen J, Long CM, Eng SM, Sagiv SK, Teitelbaum SL, Neugut AI, Santella RM Exit NIEHS 2007. Polymorphisms in nucleotide excision repair genes, polycyclic aromatic hydrocarbon-DNA adducts, and breast cancer risk. Cancer Epidemiol Biomarkers Prev 16(10):2033-2041.

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