Highlights
– Long-term consistency in meeting guideline-level physical activity (≥7.5 MET‑hours/week) was associated with marked reductions in digestive system cancer (DSC) incidence and mortality.
– Traditional dose-response models suggested optimal DSC risk reduction at ∼50 MET‑hours/week, but when long-term consistency was considered, a moderate sustained level (median ≈17 MET‑hours/week) over three decades conferred similar benefit.
– The findings support public health messages emphasizing regular, maintainable activity rather than promoting very high short-term volumes.
Background and disease burden
Digestive system cancers (DSCs) — including cancers of the oral cavity and pharynx, esophagus, stomach, small intestine, colorectum, pancreas, liver and gallbladder — account for a substantial proportion of global cancer incidence and mortality. Colorectal, pancreatic and liver cancers are among the leading causes of cancer death worldwide. Lifestyle factors, including excess adiposity, alcohol, tobacco use, diet, and physical inactivity, contribute to risk. Increasing physical activity has been linked to risk reduction for several cancers, most convincingly colorectal and breast cancer, but quantifying the optimal amount and the importance of long-term adherence for DSC prevention has been less clear.
Study design
The study by Zhang et al. (JAMA Oncology, 2025) pooled individual-level data from three large U.S. prospective cohorts: the Health Professionals Follow‑Up Study (HPFS; men), the Nurses’ Health Study (NHS; older women), and the Nurses’ Health Study II (NHSII; younger women). Participants were free of cancer and cardiovascular disease at baseline and were followed biennially for up to 32 years (1988–2021). Leisure-time physical activity was assessed repeatedly with validated questionnaires and expressed in metabolic equivalent task (MET) hours per week. The investigators examined both cumulative average activity and a novel measure of long-term consistency, defined as the percentage of follow-up years in which participants met the physical activity guideline threshold of ≥7.5 MET‑hours/week (equivalent to ≥150 minutes of moderate-intensity activity weekly).
Main outcomes were incident digestive tract cancers and cancers of digestive accessory organs, and DSC-specific mortality. Analyses adjusted for key confounders including age, sex, smoking, alcohol, diet quality, body mass index (BMI), and other established risk factors; sensitivity analyses addressed reverse causation and potential residual confounding.
Key findings
Among 231,067 participants (median baseline age 43 years), followed for up to 32 years, there were 6,538 incident DSCs and 3,791 DSC deaths. Two analytic approaches were informative.
1) Traditional dose-response (cumulative average activity)
When examining cumulative average activity, higher activity levels were associated with lower DSC incidence and mortality. Comparing the highest (≥45 MET‑hours/week) versus lowest (<3 MET‑hours/week) categories, the multivariable-adjusted hazard ratio (HR) for DSC incidence was 0.83 (95% CI, 0.74–0.93; P for trend < .001) and for DSC mortality was 0.72 (95% CI, 0.62–0.83; P for trend < .001). In separate analyses, the HRs for digestive tract cancers and digestive accessory organ cancers (pancreas, liver, gallbladder) for ≥45 vs <3 MET‑hours/week were 0.85 (95% CI, 0.75–0.97) and 0.73 (95% CI, 0.58–0.92), respectively.
Traditional dose-response modeling suggested that the nadir of DSC risk occurred at roughly 50 MET‑hours/week (≈10 times the guideline minimum), implying large volumes might be optimal if only short-term or cross-sectional measures were considered.
2) Long-term consistency in guideline adherence
The novel and clinically relevant finding emerged when the investigators considered how consistently participants met the guideline over follow-up. Consistent adherence was categorized by the percentage of follow-up years at or above ≥7.5 MET‑hours/week. Compared with participants with minimal activity, those who consistently met guideline-level activity at moderate volumes (median 16.9 MET‑hours/week; IQR 13.6–20.5) across about three decades had a significantly lower DSC incidence (HR 0.83; 95% CI, 0.75–0.90). In contrast, participants who achieved higher median volumes (38.5 MET‑hours/week; IQR 28.5–53.8) but with a similar consistency pattern did not experience additional substantial benefit beyond the moderate consistent group (HR 0.87; 95% CI, 0.81–0.93 compared with minimal activity).
In other words, sustained adherence to a moderate level of activity approximating twice the minimum guideline (around 17 MET‑hours/week, e.g., ~150–300 minutes moderate activity weekly or equivalent) over decades conferred risk reductions similar to those observed at much higher but less consistent activity volumes.
Secondary and sensitivity analyses
Inverse associations persisted across cohort strata and after excluding early follow‑up years to minimize reverse causation. Results were robust to additional adjustment for BMI (suggesting effects are not solely mediated by adiposity) and were evident for both incidence and mortality outcomes, supporting a preventive and prognostic relationship.
Interpretation and clinical implications
These results reconcile two commonly observed patterns in physical activity–cancer epidemiology. Cross-sectional or short-term measures often show increasingly lower risk with higher activity volumes, pointing to an apparent dose-response that favors high volumes. However, this study highlights that long-term, sustainable adherence to moderate activity levels may achieve much of the attainable benefit for DSC prevention and survival. This distinction matters for clinicians and public health practitioners: recommending achievable, maintainable activity patterns that patients can sustain for years or decades is likely to be more effective at the population level than promoting very high short-term volumes that many cannot maintain.
From a practical standpoint, a target of roughly 150–300 minutes/week of moderate-intensity activity (≈7.5–15 MET‑hours/week) performed consistently is a realistic goal aligned with current public health guidelines (Physical Activity Guidelines for Americans, 2nd edition, 2018) and seems sufficient to reduce DSC risk substantially when sustained over long periods.
Biological plausibility
Several mechanisms plausibly link habitual physical activity to lower DSC risk: improved insulin sensitivity and lower circulating insulin/IGF signaling; reductions in chronic systemic inflammation; favorable effects on body composition and visceral adiposity; enhanced gut motility and reduced intestinal transit time (relevant to colorectal cancer); modulation of sex hormones for hormonally responsive tumors; and improvements in immune surveillance. These pathways can operate cumulatively over years, supporting the importance of sustained behavioral patterns.
Strengths and limitations
Strengths include the large sample size, long follow-up, repeated validated measures of leisure-time activity, careful adjustment for confounders, and a novel consistency metric that increases translational relevance. Pooling three cohorts with both male and female health professionals increases internal validity but may limit generalizability to more diverse socioeconomic and racial groups. The observational design cannot prove causality, and residual confounding is possible despite extensive adjustment. Physical activity was self-reported, which may introduce measurement error; however, repeated measures likely reduce random error and misclassification of long-term patterns. Finally, while the consistency metric is compelling, it is an observational construct and may correlate with other unmeasured healthy behaviors or access to resources that support sustained activity.
Expert commentary and guideline context
Previous large pooled analyses (for example, Moore et al., JAMA Internal Medicine, 2016) have documented inverse associations between leisure-time physical activity and several cancer types. The Zhang et al. analysis advances the field by clarifying that long-term consistency at achievable activity levels delivers substantial benefit for DSCs. This aligns with public health messages emphasizing regular activity as a lifelong habit rather than sporadic high-volume exercise. Clinicians should emphasize attainable, maintainable activity prescriptions, support behavior change with counseling, and consider structural interventions to facilitate sustained activity (urban planning, workplace wellness, insurance incentives).
Conclusions and gaps for future research
Maintaining guideline-level physical activity consistently over decades appears to reduce the risk and mortality of digestive system cancers substantially, with moderate sustained volumes (~17 MET‑hours/week) providing similar benefit to much higher less consistent activity. These results support promoting achievable, long-term physical activity habits in routine clinical care and public health strategies.
Future research should investigate these associations in more socioeconomically and racially diverse populations, clarify activity-type specific effects (e.g., aerobic vs resistance), explore interactions with diet and adiposity, and test interventions to improve long-term adherence.
Funding and clinicaltrials.gov
The primary pooled analysis was funded as reported in the original publication (Zhang et al., JAMA Oncology 2025). The three contributing cohorts (HPFS, NHS, NHSII) have been supported by grants from the National Institutes of Health and other entities across decades; specific funding details are available in each cohort’s publications and the JAMA Oncology article. This was an observational epidemiologic analysis and not registered on ClinicalTrials.gov.
References
1. Zhang Y, Lee DH, Rezende LFM, Keum N, Giovannucci EL. Consistent Adherence to Physical Activity Guidelines and Digestive System Cancer Risk and Mortality. JAMA Oncol. 2025 Oct 30:e254185. doi:10.1001/jamaoncol.2025.4185.
2. Moore SC, Lee IM, Weiderpass E, et al. Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults. JAMA Intern Med. 2016;176(6):816–825. doi:10.1001/jamainternmed.2016.1548.
3. U.S. Department of Health and Human Services. Physical Activity Guidelines for Americans, 2nd edition. Washington, DC: U.S. Department of Health and Human Services; 2018.
4. World Cancer Research Fund/American Institute for Cancer Research. Diet, Nutrition, Physical Activity and Cancer: a Global Perspective. Continuous Update Project Expert Report 2018.
5. Pedersen BK, Saltin B. Exercise as medicine – evidence for prescribing exercise as therapy in 26 different chronic diseases. Br J Sports Med. 2015;49(6):? (Review discussing broad physiologic benefits of exercise relevant to chronic disease).
Author note
This article synthesizes findings from Zhang et al. (2025) and places them in clinical and public health context for clinicians, researchers, and policymakers. It aims to inform practical counseling strategies that favor sustainable activity patterns for cancer prevention.
