Synergism between occupational arsenic exposure and smoking in the induction of lung cancer.

We assembled data from numerous studies to examine whether active smoking and occupational exposure to arsenic act synergistically (more than additively) to increase the risk of lung cancer. Although several smaller studies lacked the power to reject simple additive relations, the joint effect from both exposures consistently exceeded the sum of the separate effects by about 70 to 130%. The only study not showing a greater than additive effect appeared to have inadequate data to address this question. We calculated the excess fractions for the synergism; these showed that a minimum of between 30% and 54% of lung cancer cases among those with both exposures could not be attributed to either one or the other exposure alone. Previous authors addressing the synergism between arsenic exposure and smoking have evaluated deviations from a multiplicative model, which is inappropriate for this purpose. Reports of no interaction or "negative" interaction have therefore been misleading. Taken as a whole, the evidence is compelling that arsenic and smoking act in a synergistic manner to produce lung cancer. Substantial reductions in the lung cancer burden of smokers occupationally exposed to arsenic could be achieved by reductions in either exposure. The mechanism for the synergism is unclear.