Body mass index (BMI) has been consistently, inversely associated with lung cancer risk. In our study of 778,828 individuals, we investigated if the association is explained by metabolic aberrations, residual confounding and within-person variability in smoking, and compared against other smoking-related cancers. Metabolic aberrations were proxied by a metabolic score (MS) of mid-blood pressure, glucose and triglycerides, and within-person variability in smoking (status/pack-years) was calculated from 600,201 measurements in 221,958 participants. During follow-up, w recorded 20,242 smoking-related cancers (6,735 lung cancers). Despite adjustment and correction for substantial within-person variability in smoking, BMI remained inversely associated with lung cancer. The highest lung cancer risk was composed of normal weight and high MS combined. These associations were weaker and non-significant amongst non-smokers, and similar associations were observed for head and neck cancers and oesophageal squamous cell carcinoma, but not for other generally less smoking-related cancers. We conclude that the increased lung cancer risk with low BMI and high MS is unlikely due to residual confounding and within-person variability in smoking. However, similar results for other cancers strongly related to smoking suggests a remaining, unknown, effect of smoking that may be difficult to sufficiently adjust for in observational studies. The study has been published in Cancer Epidemiology, Biomarkers and Prevention
