The Promise of Leisure-Time Physical Activity to Reduce Risk of Cancer Development

Cancer is among the leading causes ofmorbidity andmortality worldwide, with 14.1 million new cancer cases and 8.2 million cancer-related deaths in 2012.1(p3) By 2030 the global cancer burden is expected to double,with21.7millionnew cases and 13.2million cancer deaths projected due to demographic changes alone.1(p3) These estimateswill likely be compounded by the trend toward unhealthy lifestyle behaviors (eg, smoking and poor diet), particularly in emerging economies.Given that large increases in cancer incidence and mortality are expected tooccur indeveloping countrieswhere economic resources for secondaryandtertiarycareare low,primarypreventive strategies for cancer risk reductioncouldhelp to decrease the worldwide cancer burden. Asignificantproportionofcancerscouldbeprevented,and behavioral interventionsmayoffer themostcost-effective longtermcancer control options.Well-knownapproaches include tobacco use cessation, immunization against or treatment of cancer-causing infectious agents, and limiting excessive sun exposure.TheWorldCancerResearchFundestimates that20% to 25% of cancers are related to positive energy balance including overweight/obesity, poor nutrition, and/or physical inactivity.1(p6) Given that almost one-third of adults are inactive, and the proportion of inactivity appears to be increasing in low-income countries,2 physical activitymay be an important, potentially modifiable cancer risk reduction strategy. There have beennumerous studies reporting on the association between physical activity and cancer. These studies, primarily conducted in cancers of the lung, breast, prostate, colon/rectum and endometrium, show a 10% to 40% cancer risk reduction when themost physically active study participantswere comparedwith the least active participants. However, the types of physical activity (ie, leisure time, occupational, household)havevariedacross studies, anddue to small numbers, associationswith certain rare cancers are largelyunknown. Furthermore, potential modification by body size is unresolved and could be important for understanding causal associations, as well as making public health recommendations for lowering risk. The pooled analysis presented byMoore et al3 in this issue ofJAMAInternalMedicinewasundertakentodeterminethecancer risks associatedwith leisure-time physical activity and potential heterogeneity by smoking and body size. Their approach, focusing on 26 different cancer types and exploration of bodymass index (BMI, calculated asweight in kilogramsdivided by height in meters squared) as both a confounder and modifier of thephysical activity–cancer association, is innovative and provides clarity to the potentially important role of leisure-time activity in cancer prevention. One of the most important contributions of the pooled analysis undertaken by Moore and colleagues3 is the improved statistical precision to examine the physical activity– cancer association among rare malignant neoplasms. In this robust study, theauthorswereable todemonstrate that leisuretime activity was associated with reduced risk of approximately half of the cancer types examined (including 3 of the 4 cancersmost commonlydiagnosedamongmenandwomen worldwide). Furthermore, for more than one-quarter of cancer types, physical activity was associated with greater than 20% risk reduction. Importantly, the investigators controlled forwell-knowncancer-relatedrisk factorsandmoststudies (approximately 80%) used validatedmeasures of physical activity. Although this analysiswas limited to 1 type of physical activity (ie, leisure time), the evidence available todate suggests that it is unlikely that accounting for other sources (ie, occupational, transportation, and daily living) would substantially alter the findings. Another important aspect of the investigation by Moore et al3 was the examination of BMI as both a potential confounder and effectmeasuremodifier. On adjustment for BMI, associationswithphysical activitywere attenuated to thenull for 3 cancer sites (liver, gastric cardia, and endometrium), but for the remaining 10 sites associations with physical activity persisted. Moreover, after stratifying by BMI (<25 vs ≥25) the authors report significantheterogeneity (P < .01) foronly2cancer sites (lungandendometrium). Interestingly, significant risk reductionsassociatedwith increasedphysical activitywereobserved among participants with BMI of 25 or greater for both lung and endometrial cancer. Considering the fact that approximately 70% of adults in the United States4 and 40% of adults worldwide5 are overweight or obese, physical activity may serve as a promising risk reduction strategy, even among this demographic category.Moore and colleagues3 are among the first to provide evidence suggesting that, for some cancers, physical activity may act together with obesity to influence carcinogenesis. Theprecisemechanismsbywhichphysical activity influences carcinogenesis are unknown. Resolving these underlyingmechanismsshouldbeahigh researchprioritybecause this information would not only strengthen the biological plausibility of the physical activity–cancer association but could aid in identifying molecular targets for intervention. Additional research isneededto formallyevaluatewhether associations are mediated by BMI or other indices of body weight.WhereasBMI is a commonlyusedmeasureof total adiposity, other indicators (eg, waist-to-hip ratio and weight change, particularly in adulthood) may better measure central adiposity or visceral fat,which ismetabolically active and could play an integral role in tumor initiation and progresRelated article page 816 Research Original Investigation Leisure-Time Physical Activity and Risk of 26 Types of Cancer