Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study.
Embargo End Date
ICR Authors
Authors
Zhang, X
Theodoratou, E
Li, X
Farrington, SM
Law, PJ
Broderick, P
Walker, M
Klimentidis, YC
Rees, JMB
Houlston, RS
Tomlinson, IPM
Burgess, S
Campbell, H
Dunlop, MG
Timofeeva, M
Theodoratou, E
Li, X
Farrington, SM
Law, PJ
Broderick, P
Walker, M
Klimentidis, YC
Rees, JMB
Houlston, RS
Tomlinson, IPM
Burgess, S
Campbell, H
Dunlop, MG
Timofeeva, M
Document Type
Journal Article
Date
2021-03-30
Date Accepted
2020-12-08
Abstract
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.
Citation
British Journal of Cancer, 2021, 124 (7), pp. 1330 - 1338
Source Title
British Journal of Cancer
Publisher
SPRINGERNATURE
ISSN
0007-0920
eISSN
1532-1827
1532-1827
1532-1827
Collections
Research Team
Cancer Genomics