Amount and intensity of daily total physical activity, step count and risk of incident cancer in the UK Biobank

Abstract

Objectives: To investigate associations between daily physical activity, activity intensity and step counts with incident cancer risk.

Methods: Prospective analysis of UK Biobank participants who wore wrist-based accelerometers for 7 days, followed for cancer incidence (mean follow-up 5.8 years, SD 1.3). Time-series machine-learning models derived total physical activity, sedentary behaviour (SB), light-intensity physical activity (LIPA), moderate-vigorous-intensity physical activity (MVPA) and step counts. The outcome was a composite of 13 cancers previously associated with low physical activity in questionnaire-based studies. Cox proportional hazard models estimated HRs and 95% CIs, adjusted for demographic, health and lifestyle factors. We also explored associations of LIPA, MVPA and SB with cancer risk.

Results: Among 85 394 participants (median age 63 (IQR 56-68)), 2633 were diagnosed with cancer during follow-up. Compared with individuals in the lowest quintile of total physical activity (<21.6 milligravity units), those in the highest (34.3+) had a 26% lower cancer risk (HR=0.74 (95% CI 0.65 to 0.84)). After mutual adjustment, LIPA (HR=0.94 (95% CI 0.90 to 0.98)) and MVPA (HR=0.87 (95% CI 0.79 to 0.94)) were associated with lower risk, but SB was not. Similar associations were observed for substituting 1 hour/day of SB with LIPA or MVPA. Daily step counts were inversely associated with cancer, with the dose-response beginning to plateau at around 9 000 steps/day (HR=0.89 (95% CI 0.83 to 0.96) 7000 vs 5000 steps; HR=0.84 (95% CI 0.76 to 0.93) 9000 vs 5000 steps). There was no significant association between stepping intensity (peak 30-minute cadence) and cancer after adjusting for step count.

Conclusion: Total physical activity, LIPA, MVPA and step counts were inversely associated with incident cancer.

Keywords: Neoplasms; Physical activity; Sedentary Behavior.

Figure 1.. Association of mean total physical activity (milligravity units) by quintiles and physical-activity-related cancer risk in UK Biobank participants.

Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression models for quintiles of the mean total physical activity. The CIs were estimated with the floated absolute risk. The composite outcome of physical-activity-related cancer included 13 site-specific cancers (oesophageal adenocarcinoma, liver, lung, kidney, gastric cardia, endometrial, myeloid leukaemia, myeloma, colon, head and neck, rectal, bladder, and breast). Models used attained age as the underlying time variable and were adjusted for ethnicity, smoking status, alcohol consumption, deprivation, education, self-rated health, fruit and vegetable consumption, and red and processed meat consumption. The overall model was adjusted for sex. The female models were further adjusted for the use of oral contraception, use of hormone replacement therapy, and parity. The shading on the lower axis represents sample clustering in the main analytic sample. HRs are above, and the number of events is below each data point. The overall model was based on 2,633 events in 85,394 participants. The male model was based on 882 events in 37,472 participants, and the female model was based on 1,751 events in 47,922 participants.

Figure 2.. Association of mean total physical activity (milligravity units) and physical-activity-related cancer risk in UK Biobank participants, main models and sensitivity analyses.

HRs and 95% CI were estimated using Cox proportional hazard models. All models used age as the underlying time variable. The composite outcome of physical-activity-related cancer included 13 site-specific cancers (oesophageal adenocarcinoma, liver, lung, kidney, gastric cardia, endometrial, myeloid leukaemia, myeloma, colon, head and neck, rectal, bladder, and breast). The SD of the mean total physical activity in the main analytical sample was 8.3 mg. For males, the SD was 8.6mg. For females, the SD was 8.0mg. The dashed line is at the HR for the multivariable-adjusted model in the main analytical sample. Model 1: unadjusted. Model 2: adjusted for ethnicity, smoking status, alcohol consumption, deprivation, education, self-rated health, fruit and vegetable consumption, and red and processed meat consumption. The overall model was adjusted for sex. Female models were further adjusted for oral contraception, ever use of hormone replacement therapy and parity. The model without lung cancer as an outcome excluded lung cancer from the composite outcome. Model 2 stratified by smoking status was adjusted for all variables in model 2, but not smoking status. The likelihood ratio test comparing the fit between models with and without interaction terms found: For sex, the p value was 0.0003 for total PA and for smoking status, the p value was 0.02. BMI, body mass index; CVD, cardiovascular disease; FU, followup.

Figure 3.. Isotemporal substitution model for associations of time in sedentary behaviour, light intensity physical activity, and moderate-vigorous-intensity physical activity with risk of physical-activity-related cancer risk in UK Biobank participants.

Hazard ratios (HR) and 95% confidence intervals (CI) for incident physical-activity-related cancer associated with substituting time from one behaviour to another are presented. Models are isotemporal substitution models that account for time that consider time in (SB), light-intensity physical activity (LIPA), moderate-vigorous-intensity physical activity (MVPA), and wear time within the waking day. Models estimate the HR when replacing 1-hour/day of one behaviour with 1-hour/day of another, keeping total waking time constant. The composite outcome of physical-activity-related cancers included 13 site-specific cancers (oesophageal adenocarcinoma, liver, lung, kidney, gastric cardia, endometrial, myeloid leukaemia, myeloma, colon, head and neck, rectal, bladder, and breast). Models used attained age as the underlying time variable and were adjusted for ethnicity, smoking status, alcohol consumption, deprivation, education, self-rated health, fruit and vegetable consumption, and red and processed meat consumption. The overall model was adjusted for sex. Female models were further adjusted for ever use of oral contraception, ever use of hormone replacement therapy, and parity. The overall model was based on 2,633 events in 85,394 participants. The female model was based on 1,751 events in 47,922 participants, and the male model was based on 882 events in 37,472 participants.