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

Abstract

Purpose We 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). Methods We 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. Results The 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). Conclusion Our 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.

The association between basal metabolic rate and osteoarthritis: a Mendelian randomization study

“…The BMR plays a significant role in maintaining bodily functions. As such, an increase in the BMR can indicate metabolic or endocrine system disorders, and the BMR has been shown to be associated with many metabolic diseases, such as cancer and osteoporosis [ 28 , 29 ]. Diseases characterized by an immune response have also been associated with an increased BMR due to a bioenergy imbalance [ 30 ].…”

“…Several biological mechanisms can explain the positive correlation between a high BMR and OA risk. Individuals with a high BMR require more cellular energy to meet their metabolic needs [ 29 ]. Mitochondria are the main source of cellular metabolism and the mitochondrial respiratory chain is a primary source of cellular reactive oxygen species.…”

Genetically predicted basal metabolic rate and venous thromboembolism risk: a Mendelian randomization study

“…Third, among individuals of normal weight and those who are overweight, there is a positive link between BMR and proinflammatory status (30,31). Elevated BMR can contribute to the generation of inflammatory cytokines such as interleukin (IL)-6 and interferon (IFN)-γ through inducing ROS production (32). Moreover, alterations in metabolic pathways and hormonal imbalances associated with high BMR, such as insulin resistance and dyslipidemia, may also contribute to a proinflammatory state (33)(34)(35).…”

Anthropometric indicators may explain the high incidence of follicular lymphoma in Europeans: Results from a bidirectional two-sample two-step Mendelian randomisation

“…Finally, palindromically incompatible SNPs and SNPs detected using the Steiger Filter were removed 45 . A schematic of the three hypotheses of our MR study is shown in Fig.…”