REVIEW ARTICLE A Meta-Analysis of Cohort Studies Describing Mortality and Cancer Incidence among Chemical Workers in the United States and Western Europe Raymond S. Greenberg, 1 Jack S. Mandel, 2 Harris Pastides, 3 Nicole L. Britton 2 Larisa Rudenko, 4 and Thomas B. Starr 5 We evaluated the mortality and cancer experience of employ- ees of the chemical industry in the United States and western Europe, as reported in the peer-reviewed literature between 1966 and 1997 (1 million workers and 15 million person- years). Cohort studies (N = 461) were grouped (N = 181) so that specific populations could be traced from the earliest to the most recently published report, and we extracted observed and expected numbers of cases for each of 35 mortality and 23 cancer incidence endpoints. We then generated standardized mortality ratios or standardized incidence ratios and 95% con- fidence intervals, and undertook meta-analyses of subcohorts (for example, gender, latency, or duration of employment), as well as the entire cohort. With few exceptions, the observed cause-specific mortality and site-specific cancer incidences were reassuring: overall, 10% fewer deaths were observed than expected. Fewer than expected deaths from all causes, cardio- vascular disease, noncancer respiratory disease, cirrhosis of the liver, and external causes were observed, some or all of which may be attributed to a “healthy worker effect.” Meta-analyses revealed weak to moderate excesses of lung and bladder can- cers likely caused by occupational exposure to known human carcinogens. We also observed a 10 –15% increase in lym- phatic and hematopoietic cancers. Additional research is re- quired to gain a more complete understanding of the potential role that methodology and environmental or occupational influences may play in these associations. (EPIDEMIOLOGY 2001; 12:727–740) Keywords: chemical industry, worker health, cancer incidence, mortality, occupational exposures, bladder neoplasms, lower respiratory tract neoplasms, lymphohematopoietic neoplasms. Considerable attention has been given to the potential health risks to employees in chemical manufacturing and related industries. During the past several decades, hundreds of morbidity or mortality studies of chemical workers have been published, with most focused on the potential cancer risks associated with chemical exposure. Although many chemicals in general use have exhibited positive responses in cancer or noncancer rodent bioassays when tested at high doses, relatively few workplace exposures have been established as causes of cancer or other diseases in humans. Most epidemiologic studies of the workplace have documented a deficit in mortality caused by cardiovascular disease, accidents, and several other disease categories. These favorable outcomes typically are attributed to the “healthy worker effect.” Notable exceptions are the relations of bladder cancer with aromatic amines and certain dyes, liver angiosar- coma with vinyl chloride, and lung cancer with hexavalent chromium. Each of these causal associations was established because exposure to the specific chemicals was substantial and well documented. Few comprehensive studies, however, have evaluated the overall health of individuals employed in chemical manufacturing. The meta-analyses that we report herein evaluate the cause-specific mortality and cancer incidence of chemical workers in the United States and western Europe as they have been reported in the peer-reviewed literature between 1966 and 1997. These analyses do not identify specific chemicals, nor rule out their effects. Rather, they provide a general overview of the mortality and cancer incidence experience of persons employed in the chemical industry as reported in cohort studies and indicate several specific areas for future research. Subject and Methods Our starting point was the database developed by M.D. Whorton et al (1998; available from the American From the 1 Medical University of South Carolina; 2 Health and Environmental Groups, Exponent; 3 School of Public Health, University of South Carolina; 4 Integrative Biostrategies, LLC, Washington, DC; and 5 TBS Associates, Raleigh, NC. Address correspondence to: Harris Pastides, 109 Health Science Building, Build- ing 76, University of South Carolina School of Public Health, Columbia, SC 29208. This study was funded by the American Chemistry Council (Reference No. 9124). Submitted April 25, 2000; final version accepted February 27, 2001. Copyright © 2001 by Lippincott Williams & Wilkins, Inc. 727