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Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study.

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Zhang, Xiaomeng 
Theodoratou, Evropi 
Li, Xue 
Farrington, Susan M 
Law, Philip J 


BACKGROUND: We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat. METHODS: Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs. RESULTS: We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively. CONCLUSION: These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.


Funder: The Darwin Trust of Edinburgh

Funder: National Institute of Health [grant number R01 HL136528]


Adiposity, Body Mass Index, Colorectal Neoplasms, Europe, Exercise, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Obesity, Prognosis, Risk Factors, Sedentary Behavior

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Br J Cancer

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Springer Science and Business Media LLC
Wellcome Trust (204623/Z/16/Z)
Medical Research Council (MC_UU_00002/7)