Guest Update by Dr. Joseph F. Fraumeni, Jr.
NCI's Epidemiologic Research on Benzene Contributes to New EPA Rule
Since the British surgeon Percivall Pott reported in 1775 on the high frequency of scrotal cancer among chimney sweeps, studies of occupational groups have been instrumental in the discovery of environmental carcinogens and the development of preventive measures. In modern times, regulatory agencies have depended to a considerable extent on epidemiologic studies in the workplace in formulating public health policies to control hazardous exposures among both workers and the general population.
Most recently, a series of studies in NCI's Division of Cancer Epidemiology and Genetics (DCEG) was considered by the U.S. Environmental Protection Agency (EPA) in establishing a new rule to limit the benzene content in gasoline and adopt controls on passenger vehicles and portable fuel containers in order to significantly reduce emissions of hazardous air pollutants. The rule was signed and submitted to the Federal Register on February 9.
In developing this policy, EPA was influenced by the results of a 20-year collaborative research program in which DCEG investigators worked closely with scientists at the Chinese Center for Disease Control and Prevention (or CDC, formerly known as the Chinese Academy of Preventive Medicine). The goal of this study was to evaluate the cancer risks in a large cohort of Chinese workers heavily exposed to benzene, a known carcinogen that is widely prevalent in the environment. Using detailed exposure assessment data, the cohort study, published in the Journal of the National Cancer Institute (1997), was able to uncover an increased risk of acute nonlymphocytic leukemia and myelodysplastic syndrome at exposures below 10 parts per million (ppm). There was also evidence linking benzene to other forms of leukemia and possibly non-Hodgkin lymphoma.
These findings were followed by molecular epidemiology studies utilizing a panel of biomarkers to help identify the underlying mechanisms of benzene-related leukemia, including precursor conditions and susceptibility states. It was reported in the American Journal of Industrial Medicine (1996) that hematologic toxicity occurred at lower levels of benzene exposure than generally appreciated. This prompted a larger study published in Science (2004) that uncovered hematotoxicity among workers exposed to levels under 1 ppm in the air, the current U.S. occupational standard. In addition, variants in several genes were associated with a greater decrease in white blood cell counts among exposed workers.
While this long-term collaborative U.S.-China project focused on the hazards of benzene in the workplace, it is known that large segments of the population around the world are exposed to small amounts of benzene on a daily basis, especially through inhaled air that contains benzene from vehicular and other sources. Thus, the quantitative dose-related health effects from workplace exposures have contributed not only to lowering the benzene occupational standard in China, but also to guiding the risk assessment process leading to controls on environmental benzene exposure in the United States.In addition to several intramural investigators at NCI, this binational collaboration involved a team of Chinese investigators led by Drs. Songnian Yin and Guilan Li from the Chinese CDC. The molecular epidemiology components also included Drs. Martyn Smith, Luoping Zhang, and Stephen Rappaport, at the University of California, Berkeley.