A Mendelian randomization study confirmed a causal relationship between high basal metabolic rate levels and increased risk of lung cancer

Abstract

Abstract Purpose We conducted a two-sample Mendelian randomization (MR) study and performed a reverse causation test to assess the potential causal relationship between basal metabolic rate (BMR) and lung cancer, intending to determine whether genetically predicted BMR levels are a causal factor for lung cancer.Methods We collected data on single nucleotide polymorphisms (SNPs) related to basal metabolic rate (BMR) and lung cancer throughout the whole genome. A total of 599 strongly associated SNPs were selected as proxies for BMR to assess the causal relationship between BMR levels and increased risk of lung cancer. Stratified analyses were performed on different histological types of lung cancer to explore the causal relationship between BMR and non-small cell lung cancer/small cell lung cancer risk. The statistical effect was calculated using the Inverse Variance-Weighted(IVW)method, and sensitivity analysis was conducted to assess pleiotropy and heterogeneity.Result The IVW method determined a potential causal relationship between high BMR levels and lung cancer (OR = 1.23, 95%CI = 1.06–1.43, p < 0.01), while dismissing a reverse causal relationship (OR = 1.00, 95%CI = 0.98–1.01, p = 0.63). The causal relationship between high BMR levels and NSCLC was also confirmed (IVW: OR = 1.32, 95%CI = 1.01–1.74, p < 0.05). Further sensitivity analysis validated the stability of these results.Conclusion Our study results provide the first evidence of a causal relationship between high BMR levels and the risk of lung cancer. Additionally, a positive association between high BMR levels and NSCLC risk was observed, while no relation was found with SCLC, possibly due to the lack of data.