Leanness and lung cancer risk: fact or artifact?

Background: More than a dozen studies have examined the association between leanness and increased lung cancer risk. None of the prospective studies has been large enough to allow exclusion of smokers or persons with preexisting disease, two factors that cause both leanness and poor survival and thus may cause a spurious association between low body mass index and fatal lung cancer.
Methods: Using Cox proportional hazards models, we examined this issue in a cohort of 941,105 U.S. adults enrolled in an American Cancer Society prospective study in 1982. During 14 years of follow-up, 14,066 people died of lung cancer.
Results: In analyses restricted to lifelong nonsmokers who did not report preexisting disease, leanness was not substantially associated with lung cancer mortality in men (rate ratio = 0.9; 95% confidence interval = 0.3-3.1) or in women (rate ratio = 1.2; 95% confidence interval = 0.7-2.1). However, leanness was associated with increased lung cancer risk in analyses that attempted to control for, rather than exclude, smokers and persons with preexisting disease.
Conclusions: These data suggest that the association between leanness and lung cancer mortality is not causal but rather is an artifact of the effects of smoking and preexisting disease.