Associations between potential causal factors and colorectal cancer risk: A systematic review and meta‐analysis of Mendelian randomization studies

Objective To summarize the associations between potential causal factors and colorectal cancer (CRC) risk based on existing Mendelian randomization studies. Methods This systematic review and meta‐analysis involved a literature search in Embase and Medline. All published articles using Mendelian randomization to explore potential causal factors of CRC were included. Studies that reported Mendelian randomization estimates of standard deviation changes in exposures were included in the meta‐analysis. Subgroup analyses based on sex and anatomical sites were performed. Results One hundred and ninety studies presented in 51 articles were included in systematic review, and 114 studies conducted in 32 articles were included in the meta‐analysis. Adult body mass index, waist circumference, waist hip ratio, body height, body fat percentage, arm fat ratio, childhood obesity, lifetime cigarette consumption, short sleep, coffee consumption, and blood levels of vitamin B 12 , arachidonic acid, stearic acid, and insulin‐like growth factor binding protein 3 were positively associated with CRC risk. Conversely, acceleration–vector–magnitude physical activity, milk consumption, and blood levels of adiponectin, linoleic acid, α‐linolenic acid, oleic acid, palmitoleic acid, interleukin‐6 receptor subunit‐α, and tumor necrosis factor were inversely associated with CRC risk. Conclusions Most obesity‐related anthropometric characteristics, several unhealthy lifestyles, and blood levels of some micronutrients, fatty acids, and diabetes‐related biomarkers were positively associated with CRC risk. In contrast, some lifestyles and blood levels of some fatty acids and inflammatory biomarkers were inversely associated with CRC risk. Future studies with more valid genetic variants are needed for factors with discrepancies between Mendelian randomization and epidemiological studies.