Silica and Lung Cancer When Is Enough Evidence Enough

lhe case-control study presented in this issue of Epidemiology by Cassidy et all I provides striking evidence of an association between occupational exposure to crys talline silica and lung cancer. The study not only demonstrated an overall positive association, but also very strong evidence for an exposure-response relationship. These findings are not themselves very surprising or novel given that similar findings have been reported in numerous previous studies. What makes these findings most remarkable is that they come from a population-based casecontrol study. This study design has rarely been capable of demonstrating convincing evidence for associations for exposures to occupa tional carcinogens due to low power and poor exposure classification stemming from their reliance on self-reported exposures. These studies have been of particularly limited use in demonstrating exposure-response relationships. In large part the success of this study is due to the unusually detailed questionnaires on work histories that were used. In addition to collecting complete work histories, the study included "specialized questionnaires" for specific jobs designed to yield additional information on silica and the 69 other occupa tional exposures. The study's exposure assessment was clearly also enhanced by the detailed review by a group of industrial hygiene experts. Overall this study, along with the work of Siemiatycki,2 provides a model for how population-based studies can be useful for studying occupational exposures and diseases. The authors are somewhat circumspect in their conclusions as most epidemiologists are prone to be. They state that, "Overall, these results are consistent with a causal interpretation of the association between exposure to silica and lung cancer." However, this tentativeness in their conclusions may be too restrained. After all, the International Agency for Research on Cancer (IARC),3 the National Institute for Occupational Safety and Health (NIOSH),4 and the National Toxicology Program (NTP)5 have all concluded that exposure to respirable crystalline silica is a known human carcinogen. (IARC and NIOSH qualified this conclusion as being carcinogenic in occupational settings.) The authors note that, despite these pronouncements by authoritative organizations, some authors have disagreed with these conclusions6 and that a controversy still persists because not all studies have been consistent in observing an association or an exposure-response relationship or have adequately controlled for potential confounding exposures. However, how credible are these arguments against a causal interpretation? Although most epidemiologic studies have observed a positive association between exposures to crystalline silica and lung cancer,7 there have been some notable exceptions. For example, studies of coal miners who are exposed to crystalline silica have not generally demonstrated an increased lung cancer risk,8'9 which may be explained by the coating of silica in mines by clay. It is likely, as noted by IARC, that the carcinogenicity of crystalline silica "may be dependent on inherent characteristics of the crystalline silica or on external factors affecting its biologic activity."3 In fact, the situation with silica may be viewed as quite analogous to that for asbestos, which has also not been consistently associated with an increased risk of lung cancer in all studies. For example, asbestos