A Case-Cohort Study of Hematopoietic Malignancies and Related Disorders and Lung Cancer in Benzene-Exposed Workers in China
Condition: Lung Cancer; Lymphoma; Acute Non-Lymphocytic Leukemia; Benzene Poisoning; Leukemia
MeSH terms: Leukemia; Lung Neoplasms; Hematologic Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Poisoning
Study type: Observational

Summary: 
      This study will examine the risks of workplace exposure to benzene, a substance known to lead
      to cancer of the blood and possibly of the lungs. It is used widely in industries and is a
      contaminant in the environment. Researchers from the National Cancer Institute and the China
      Center for Disease Control (formerly Chinese Academy of Preventive Medicine) had done
      previous studies of workers in manufacturing industries in China of people who worked at
      least 1 day from 1972 to 1987 in 12 cities in that country. Data were collected of
      approximately 75,000 workers exposed to benzene and 35,000 who were not, with the purpose of
      investigating the relationship between benzene exposure and cancer risk. For workers exposed
      to benzene, there was a significant risk of cancer affecting the blood cells and a 1.8-fold
      excess of lung cancer among them. This study will expand those findings and also identify the
      effects of benzene amounts and whether there is a genetic tendency for benzene poisoning.
      About 3,860 benzene-exposed workers from the 12 cities will be interviewed. Next-of-kin of
      deceased workers, and a subcohort (additional grouping) of participants will serve as a
      control group in the research.

      Patients who have worked at places where there was exposure to benzene will have a brief
      physical exam and samples of cells from a mouth rinse and samples from blood will be
      collected to study the genetic influence on developing blood diseases from workplace
      exposures.

      All participants or next-of-kin, for deceased, will be given a questionnaire about their work
      history, use of cigarettes and hair dyes, medications they take, and family history of
      cancer. Interviews of about 40 minutes long will be conducted at participants homes or
      workplaces, at a time convenient to them, and the interviews will be audiotaped.
    

Detailed description: 
      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.
    

Observational model: Cohort
Time perspective: Retrospective
Sampling method: Probability Sample
Study population: 
        From a cohort of 74,827 benzene-exposed and 35,804 unexposed workers employed (Bullet) one
        month in several industries and followed up during 1972-99, we identified a case-cohort
        population that included incident and deceased cases with hematopoietic malignancies
        diagnosed during those same years among exposed and unexposed workers and a 1,500 worker
        subcohort (1,100 exposed, 400 unexposed). The subcohort was selected by stratified random
        sampling (by sex, exposure status, and age at start of follow-up) from 106,641 of the
        cohort members. Other outcomes to be evaluated include incident cases with benzene
        hematotoxicity and deaths from lung cancer.
      
Keywords: Case-Cohort Study; Leukemia; Lymphoma; Benzene; Blood Disorders; Solvent Exposure; Cancer Risk