Cancer Epidemiol Biomarkers Prev. 2021 Jun 22:cebp.0058.2021. doi: 10.1158/1055-9965.EPI-21-0058. Online ahead of print.
ABSTRACT
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.
PMID:34162656 | DOI:10.1158/1055-9965.EPI-21-0058
