A Case - Cohort Study of Hematopoietic Malignancies and Related Disorders and Lung Cancer in Benzene-Exposed Workers in China

Benzene is a known leukemogen and may cause lymphoma as well, but its ability to , cause these conditions below 10 parts per million (ppm) in air are unclear. It is currently regulated in the United States at 1 ppm as an 8-hour time-weighted average and at a 5 ppm short-term exposure level for 15 minutes. There is a critical need to assess risks related to benzene exposure under 10 ppm because it is widely used industrially and a ubiquitous contaminant in the environment.

The National Cancer Institute (NCI) and the Chinese Academy of Preventive Medicine (CAPM), whose name was recently changed to the China Center for Disease Control (CDC) previously established a cohort of 75,000 workers exposed to benzene in 12 cities in China and 35,000 unexposed comparison workers, to investigate the relationship between benzene exposure and cancer risk, from 1972 to 1987. We followed up each worker using factory records and reported results suggesting that benzene exposure under 10 ppm may be associated with increased risk of acute non-lymphocytic cancer and could also be associated with increased risk of lymphoma and lung cancer. We have now laid the groundwork for a further epidemiologic investigation in China to evaluate health risks from lower levels of benzene exposure, particularly as present in the factories during the 1990s. The cohort was followed up through 1999, and through this effort we have identified 3260 subjects for study, including cases (HLD malignancies, n= 161; benzene poisoning, n= 1040; lung cancer, n= 560) and 1500 subjects in a cohort sub-sample to be used as the comparison group. In addition, we have identified a series of cases with benzene poisoning and controls from the same factories outside of the cohort (n = 600).

We propose to contact next-of-kin of deceased subjects (essentially all cancer cases and some members of the sub-cohort are deceased), for questionnaire-based evaluation of benzene and other exposures, and to contact living subjects (primarily the benzene poisoning cases and the sub-cohort sample) for collection of questionnaires and biologic samples. The questionnaires (formatted for direct interview of living subjects or for next-of-kin) will collect information on potential confounders needed in the analysis of benzene's effects and information on work experience outside of the study cohort factories. The biologic sample collection (13 ml blood and buccal cell rinse) will provide material primarily for study of genetic polymorphisms potentially associated with benzene metabolism and disease status. The polymorphisms being studied are relatively common in the Chinese population and may be associated with a relatively modest increase in risk (1.5 to 2-fold). Written informed consent will be obtained from all next-of-kin and all live study subjects. We will attempt to enroll 3,860 study subjects or next-of-kin. The study will be carried out with Drs. Gui-Lan Li and Song-Nian Yin and colleagues from the China CDC, Beijing, China.