The inverse association of body mass index with lung cancer: exploring residual confounding, metabolic aberrations and within-person variability in smoking
Menée auprès de 778 828 personnes (durée médiane de suivi : 20 ans), cette étude analyse l'association entre l'indice de masse corporelle, un score métabolique de la pression artérielle moyenne et le risque de cancer du poumon (6 735 cas) ou d'autres cancers liés au tabagisme (13 507 cas)
Background: The inverse observational association between body mass index (BMI) and lung cancer risk remains unclear. We assessed whether the association is explained by metabolic aberrations, residual confounding and within-person variability in smoking, and compared against other smoking-related cancers. Methods: We investigated the association between BMI, and its combination with a metabolic score (MS) of mid-blood pressure, glucose and triglycerides, with lung cancer and other smoking-related cancers in 778,828 individuals. We used Cox regression, adjusted and corrected for within-person variability in smoking (status/pack-years), calculated from 600,201 measurements in 221,958 participants. Results: Over a median follow-up of 20 years, 20,242 smoking-related cancers (6,735 lung cancers) were recorded. Despite adjustment and correction for substantial within-person variability in smoking, BMI remained inversely associated with lung cancer (hazard ratio per standard deviation increase, 0.87 [95% confidence interval 0.85-0.89]). Individuals with BMI<25 kg/m2 and high MS had the highest risk (hazard ratio 1.52 [1.44-1.60] vs BMI{greater than or equal to}25 with low MS). These associations were weaker and non-significant amongst non-smokers. Similar associations were observed for head and neck cancers and oesophageal squamous cell carcinoma, whereas for other smoking-related cancers, we generally observed positive associations with BMI. Conclusions: 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. Impact: Extensive smoking-adjustments may not capture all the effects of smoking on the relationship between obesity-related factors and risk of smoking-related cancers.