When to be skeptical of negative studies: Pitfalls in evaluating occupational risks using population-based case-control studies

This study investigated arsenic and lung cancer incidence in a community se tting in the Montreal area. Job histories and sociodemographic factors were collected by interview from 857 lung cancer cases, 533 general population controls, and 1,360 controls with other cancers. Chemist-hygienists assesse d each subject's life-time occupational exposure to 294 substances. Logisti c regressions yielded arsenic/lung cancer odds ratios of 1.1 (95% confidenc e interval = 0.60, 1.7) based on cancer controls, and 0.82 (95% confidence interval = 0.41, 1.6) based on population controls. Risk did not rise with increasing level or probability of exposure. Worksite studies consistently show lung carcinogenicity from arsenic. Since confounding from other chemicals was well controlled, the most likely expl anation is substantially lower exposures than in previous studies. The lack of association in this study demonstrates the need for caution in interpre ting negative findings from population-based case-control studies, particul arly when exposures are low or rate, as well as the difficulty in generatin g hypotheses from such studies.