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This subject has long been bedevilled by unwarrantable assumption and circular argument. Why should there be only two possible hypotheses of interaction (additive and multiplicative)? Theory expects multiplicativity; epidemiology can seldom reject this hypothesis; so theory is “accepted”, and deviations from multiplicativity must be explained away. Resolution is made especially difficult because the nature of the data imposes very large error; also it has to be assumed that the exposed smoked as many cigarettes as the unexposed, and that smokers and non-smokers were exposed equally.
Thus the “comprehensive” review by Lee1 was to be welcomed. However, discrepancies, particularly with another review,2 demanded discussion: this letter is the result.
From almost 40 “results” in 25 reports, Lee makes two selections to confirm the well known facts that asbestos can increase lung cancer risk in non-smokers and that the additive theory (of independent action) does not explain many of the data. Then, for 16 results, Lee calculates a statistic V; for an observed multiplicative interaction, V = 1. The weighted average V = 0.90 (95% CI: 0.67 to 1.20) leads to Lee's conclusion.1 Repair of (acknowledged) imperfections (one misquoted result; two incorrect omissions) reduced V only slightly, to 0.83 (95% CI: 0.63 to 1.08); for nine cohorts and nine case–referent studies, respectively, V = 0.63 and 1.08, a “significant” difference (p = 0.049).
There are, however, other imperfections: two cohorts3,4 broke the rule of independence; in another,5 asbestos had a minuscule (protective) effect on lung cancer …