Lung cancer and multiple exposures.

To the Editor: We would like to thank Moolgavkar et aP for their provocative and informative article on lung cancer and its relation to radon exposure and cigarette smoke. Their observations supporting a two-mutation model for both tobacco and radon may help to explain some of the confusing observations regarding respirable crystalline silica, . tobacco smoke, and the development of pulmonary neoplasia. Some epigemiologic studies observed no association between lung cancer and the inhalation of crystalline silica, • but others provide strong evidence of increased risk of lung cancer among miners and other occupationally exposed individuals. 4-7 Some studies indicate synergistic action between tobacco smoke and respirable crystalline silica, 7 whereas others state more emphatically that a multiplicative relation exists. The interaction from simultaneous tobacco smoke and respirable crystalline silica has been discussed, but as yet it is difficult to describe explicitly; whether the relation is additive, multiplicative, or supra-additive, similar to the radon-cigarette smoke interaction as observed by Moolgavkar et al, is undetermined. Most of the occupational exposure studies of crystalline silica and lung cancer do not include industrial hygiene measures of radon, polycyclic aromatic hydrocarbons, or other possible covariates or confounders of lung cancer; some do mention these factors in their discussion.• Analogously, as elucidated by Abelson, many of the studies of uranium miners have focused on radon and tobacco smoke exposure and have neglected dust or respirable particulates and crystalline silica as possible covariates or confounders. Does crystalline silica need to be included in the lung cancer model for all underground miners, regardless of the ore type? Similar to the inverse relation between exposure levels and lifetime tumor probability observed by Moolgavkar et al, 1 experimental animal studies of inhaled crystalline silica have demonstrated lower rates of cancer at higher doses and/ or longer fractional lifetime exposures. 13 One epidemiologic study observed higher odds ratios for the development of lung cancer at lower cumulative silica dust exposures. As proposed for radon and tobacco smoke, can we simi-