Physical activity and risks of breast and colorectal cancer: A Mendelian randomization analysis

Papadimitriou, Nikos; Dimou, Niki; Tsilidis, Konstantinos K.; Banbury, Barbara L.; Martin, Richard M; Lewis, Sarah J.; Kazmi, Nabila; Robinson, Timothy; Albanês, Demetrius; Aleksandrova, Krasimira; Berndt, Sonja I.; Bishop, D. Timothy; Brenner, Hermann; Buchanan, Daniel D.; Bueno‐de‐Mesquita, Bas; Campbell, Peter T.; Castellví–Bel, Sergi; Chan, Andrew T.; Chang‐Claude, Jenny; Ellingjord-Dale, Merete; Figueiredo, Jane C.; Gallinger, Steven; Giles, Graham G.; Giovannucci, Edward; Gruber, Stephen B.; Gsur, Andrea; Hampe, Jochen; Hampel, Heather; Harlid, Sophia; Harrison, Tabitha A.; Hoffmeister, Michael; Hopper, John L.; Hsu, Li; Huerta, José María; Huyghe, Jeroen R.; Jenkins, Mark A.; Keku, Temitope O.; Kühn, Tilman; Vecchia, Carlo La; Marchand, Loı̈c Le; Li, Christopher I.; Li, Li; Lindblom, Annika; Lindor, Noralane M.; Lynch, Brigid M.; Markowitz, Sanford D.; Masala, Giovanna; May, Anne M.; Milne, Roger L.; Monninkhof, Evelyn M.; Moreno, Lorena; Newcomb, Polly A.; Offit, Kenneth; Perduca, Vittorio; Pharoah, Paul D.P.; Platz, Elizabeth A.; Potter, John D.; Rennert, Gad; Riboli, Elio; Sánchez, María‐José; Schmit, Stephanie L.; Schoen, Robert E.; Severi, Gianluca; Sieri, Sabina; Slattery, Martha L.; Song, Mingyang; Tangen, Catherine M.; Thibodeau, Stephen N.; Travis, Ruth C.; Trichopoulou, Antonia; Ulrich, Cornelia M.; Duijnhoven, Fränzel J. van; Guelpen, Bethany Van; Vodička, Pavel; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Peters, Ulrike; Gunter, Marc J.; Murphy, Neil

doi:10.1101/762484

Cited by 5 publications

(5 citation statements)

References 44 publications

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“…Our findings are in accordance with previous research showing an inverse relationship between physical activity level and incident breast [10,13,15,71,72] and colon [7,10,[72][73][74] cancers. Our findings are also supported by previous UK Biobank studies examining the association of physical activity, including studies using Mendelian Randomisation methods or accelerometerderived physical activity levels, with breast or colon cancer incidence [7,75,76].…”

Section: Relation Of Findings To Previous Researchsupporting

confidence: 87%

Physical activity and cancer risk: Findings from the UK Biobank, a large prospective cohort study

Murray

Coleman

Hunter

2020

Cancer Epidemiology

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Highlights▪ Moderate physical activity levels were associated with lower risk of oropharyngeal and lung cancers ▪ High physical activity levels were associated with lung, breast, hepatobiliary and colon cancers ▪ Sensitivity analyses showed associations with lower oesophageal and higher prostate cancer incidence ▪ Results varied by deprivation, smoking, or combined body fat and physical activity ▪ Promoting high levels of physical activity may be required for cancer prevention ABSTRACT Objectives: This study aimed to investigate the association between physical activity and site-specific cancer incidence.Methods: UK Biobank is a prospective population-based cohort study. 364,899 adults (51.6% females, mean age 56.0 years) were included. The exposure variable was physical activity level derived from the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Participants were categorised at 'high' (≥1,500 MET-minutes/week), 'moderate' (≥600 MET-minutes/week) or 'low' levels of activity following standardised IPAQ-SF scoring guidance. Primary outcome measures included incident cancers at 20 sites. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) showing relationships between physical activity and cancer.Results: 21,816 incident cancers were identified. Significant associations were identified between high physical activity levels and lower risk of lung (HR 0.81, 95% CI: 0.70, 0.94), breast (female only) (HR 0.85, 95% CI: 0.77, 0.94), hepatobiliary tract (HR 0.72, 95% CI: 0.53, 0.97), and colon (HR 0.86, 95% CI: 0.74, 0.99) cancers compared to low physical activity levels. Moderate levels of physical activity were associated with significantly lower risk of oropharyngeal (HR 0.71, 95% CI: 0.55, 0.93), and lung cancer (HR 0.86, 95% CI: 0.74, 0.99) compared to low physical activity levels. Sensitivity analyses showed associations of higher physical activity with lower oesophageal and higher prostate cancer incidence. Conclusions:Regular physical activity is significantly associated with reduced risk for lung, breast, hepatobiliary tract, colon and oropharyngeal cancers. Our findings highlight the importance of physical activity promotion, particularly high levels of physical activity, in cancer prevention.

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Section: Relation Of Findings To Previous Researchsupporting

confidence: 87%

Physical activity and cancer risk: Findings from the UK Biobank, a large prospective cohort study

Murray

Coleman

Hunter

2020

Cancer Epidemiology

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“…20 The variance (R 2 ) in each exposure explained by SNPs was calculated through the formula as previously described. 39 We also approximated the F statistics to quantify the strength of genetic instruments, with F statistics .10 considered to avoid weak instrument bias. 8 Data harmonization was made to ensure the alignment of SNP allele for the exposure and the outcome.…”

Section: Instrument Selection and Harmonizationmentioning

confidence: 99%

Multisite chronic pain as a causal risk factor for coronary artery disease: findings from Mendelian randomization

Zhu

Wang²,

Liu

et al. 2022

Pain

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“…The a priori statistical power was calculated using an online tool at http://cnsgenomics.com/shiny/mRnd/ [18]. We assumed that the eight accelerometer-based physical activity SNPs explained 0.4% of the phenotypic variable [16,19,20]. Given a type 1 error of 5%, we had sufficient statistical power (>85%) for an expected odds ratios (OR) per 1 standard deviation of ≤ 0.88 between AD and genetically instrumented accelerometerbased physical activity.…”

Section: Statistical Powermentioning

confidence: 99%

Physical activity and risk of Alzheimer disease

et al. 2020

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Objective:Evidence from observational studies for the effect of physical activity on the risk of Alzheimer’s disease (AD) is inconclusive. We performed a two-sample Mendelian randomization analysis to examine whether physical activity is protective for AD.Methods:Summary data of genome-wide association studies on physical activity and AD were used. The primary study population included 21,982 AD cases and 41,944 cognitively normal controls. Eight single nucleotide polymorphisms (SNPs) known at P<5x10-8 to be associated with ‘average accelerations’ and eight SNPs associated at P<5x10-7 with vigorous physical activity (‘fraction of accelerations >425 milli-gravities’) served as instrumental variables.Results:There was no association between genetically predicted ‘average accelerations’ with the risk of AD (inverse variance weighted odds ratio [OR] per standard deviation (SD) increment: 1.03, 95% confidence interval: 0.97-1.10, P=0.332). Genetic liability for ‘fraction of accelerations >425 milli-gravities’ was unrelated to AD risk.Conclusion:The present study does not support a causal association between physical activity and risk of AD.

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Physical activity and risks of breast and colorectal cancer: A Mendelian randomization analysis

Cited by 5 publications

References 44 publications

Physical activity and cancer risk: Findings from the UK Biobank, a large prospective cohort study

Physical activity and cancer risk: Findings from the UK Biobank, a large prospective cohort study

Multisite chronic pain as a causal risk factor for coronary artery disease: findings from Mendelian randomization

Physical activity and risk of Alzheimer disease

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