A bidirectional Mendelian randomization study supports the causal effects of a high basal metabolic rate on colorectal cancer risk.

Abstract

PurposeWe conducted a bidirectional two-sample Mendelian randomization (MR) study to determine whether genetically predicted basal metabolic rate (BMR) was a causal risk factor for colorectal cancer (CRC) or whether a genetically predicted CRC risk can influence the BMR level (i.e., reverse causation).MethodsWe employed 1,040 genetic variants as proxies for BMR to obtain effect estimates on CRC risk. Another 58 CRC-associated variants were used to estimate effects on BMR levels. Stratified analysis by tumor site was used to examine the causal associations between BMR and colon/rectal cancer risk.ResultsThe inverse variance weighted (IVW) method indicated a significant causal effect of genetically determined BMR on CRC risk (ORSD = 1.27, 95% CI = 1.07–1.51). No significant reverse causal association was identified between genetically increased CRC risk and BMR levels [IVW (β = 0, 95% CI = -0.01 to 0)]. The results of MR-Egger and the weighted median method were consistent with the IVW method. Stratified analysis by CRC sites identified significant causal associations between BMR and colon cancer [IVW (ORSD = 1.45, 95% CI = 1.16-1-80)], and null evidence of a causal association between BMR and rectal cancer risk was found (p > 0.05).ConclusionOur findings add to the current literature by validating a positive relationship between high BMR levels and CRC risk instead of reverse causality. The genetically predicted BMR level was causally associated with colon cancer risk but not rectal cancer risk.