A Pilot Case-Cohort Study of Liver and Pancreatic Cancers in Poultry Workers MARTHA FELINI, PHD, ERIC JOHNSON, PHD, NYKICONIA PREACELY, DRPH, VISHNU SARDA, MBBS, HARRISON NDETAN, DRPH, AND SARITHA BANGARA, MPH PURPOSE: To test the hypothesis that exposure to poultry oncogenic viruses that widely occurs occupa- tionally in poultry workers and in the general population, may be associated with increased risks of deaths from liver and pancreatic cancers, and to identify new risk factors. METHODS: A pilot case-cohort study of both cancers within a combined cohort of 30,411 highly exposed poultry workers and 16,408 control subjects was conducted, and risk assessed by logistic regression odds ratios (OR) and proportional hazards risk ratios. RESULTS: New occupational findings were recorded respectively for pancreatic/liver cancers, for slaugh- tering of poultry (OR Z 8.9, 95% confidence interval [CI]: 2.7–29.3)/OR Z 9.1, 95% CI: 1.9–42.9); catching of live chickens (OR Z 3.6, 95% CI: 1.2–10.9)/OR Z 1.0, 95% CI: 0.1–8.5); killing other types of animals for food (OR Z 4.8, 95% CI: 1.5–16.6)/OR Z 2.0, 95% CI: 0.2–18.2), and ever worked on a pig raising farm (OR Z 3.0, 95% CI: 1.0–8.2) for pancreatic cancer only. New non-occupational findings for liver cancer were for receiving immunization with yellow fever vaccine (OR Z 8.7, 95% CI: 1.0–76.3); and vaccination with typhoid vaccine (OR Z 6.3, 95% CI: 1.1–37.4). The study also confirmed previously reported risk factors for both diseases. CONCLUSIONS: This study provides preliminary evidence that exposure to poultry oncogenic viruses may possibly be associated with the occurrence of liver and pancreatic cancers. Case-control studies nested within occupational cohorts of highly exposed subjects of sufficient statistical power may provide an efficient and valid method of investigating/confirming these findings. Ann Epidemiol 2011;21:755–766. Ó 2011 Elsevier Inc. All rights reserved. KEY WORDS: Oncogenic Viruses, Pancreas, Poultry, Occupation, Liver, Cancer, Risk Factors. INTRODUCTION Certain viruses naturally infect and cause cancer in chickens and turkeys. They include the avian leukosis/sarcoma viruses (ALSV), reticuloendotheliosis viruses, and Marek’s disease virus. Some of these viruses are among the most potent cancer-causing agents known in animals (1). Hu- mans are widely exposed to these viruses from contact with live poultry and their raw products including eggs; from ingestion of raw or inadequately cooked products; or through vaccination with vaccines grown in eggs, such as measles, mumps, influenza, yellow fever, and typhus vaccines (2–7). It has been shown that exogenous ALSV- contaminated yellow fever vaccines caused malignant tumors when injected into chickens (8). Some (9–11) but not all studies (4, 5, 12) have reported the presence of anti- bodies to these viruses in the sera of poultry workers and subjects in the general population. It is known that the viruses can infect/transform human cells in vitro (13–15). However, despite these observations, it is not known if they cause cancer in humans, partly because of the lack of analytic epidemiologic studies. To explore if the development of cancer is associated with exposure to these viruses, we studied mortality in 30,411 workers from 23 poultry slaughtering and processing plants located in seven states in the United States, that were identified from three main sources/cohorts: (1) the United Food and Commercial Workers (UFCW) local union in Baltimore, Maryland; (2) the UFCW local poultry union in Marshall, Missouri; and (3) a UFCW Pension Fund that covered poultry plants in six states (Alaska, Arkansas, Louisiana, Maine, Missouri, and Texas). These workers have one of the highest known human exposures to these viruses. In addition to the poultry workers, the rosters of the Baltimore union and the Pension Fund also contained a total of 16,408 members who worked in various nonpoultry companies located in Maryland, Florida, Illinois, Indiana, Massachusetts, New Jersey, Ohio, Pennsylvania, and Texas. Excess occurrence of 11 cancer sites, including liver and pancreatic cancers, was observed in the poultry workers (16–20). Accordingly, we conducted a pilot case-cohort From the Department of Epidemiology (M.F., E.J., N.P., S.B.); and Department of Biostatistics (V.S., H.N.), UNT Health Sciences Center School of Public Health, Fort Worth, TX. Address correspondence to: Dr. Eric S. Johnson, PhD, Department of Epidemiology, School of Public Health, UNT Health Sciences Center, 3500 Camp Bowie Blvd., Fort Worth, TX 76107. Tel.: þ1-817-735-0327; Fax: þ1-817-735-0443. E-mail: Eric.Johnson@unthsc.edu. Received March 29, 2011. Accepted July 6, 2011. Ó 2011 Elsevier Inc. All rights reserved. 1047-2797/$ - see front matter 360 Park Avenue South, New York, NY 10010 doi:10.1016/j.annepidem.2011.07.001