Physical Activity and Digestive System Cancer Risk: Still Chasing the Promise.

The promise of health behaviors to prevent cancer was established in the landmark 1981 publication byDoll andPeto,1who estimatedthat30%ofcancerdeathswereattributabletolifestyle and environmental factors. ThoughDoll and Peto did not addressphysicalactivityorexercise, shortly thereafter, in 1984, another landmark publication by Garabrant et al2 established physical activity as a potential major factor related to colon cancer risk. In that study, the authors observed thatmen diagnosedwith colon cancerweremore likely than noncancer controls tohaveoccupations requiring lowlevelsofphysical activity. Numerous subsequent observational studies and,more recently, randomizedcontrolledtrialshave interrogatedtherole of physical activity and other lifestyle behaviors as risk factors related to a range of cancers.3,4 The relationship between physical activity and digestive system cancers has been of particular interest because physical activity may affect the functioning of the whole gastrointestinal tract. These include local effects, such as diluting potentiallycarcinogenicbileacidsanddecreasing intestinal transit time, thereby limiting thetimepotential carcinogensare incontactwith the gut.5 Physical activitymayalsohave systemic effects, such as increasing immune function and decreasing inflammation, insulin resistance, and circulating sex hormones,5,6 which have been linked to carcinogenesis. But which of thesemechanisms is the key factor to preventing digestive systemcancers, or the combinations that are themost important, is not known. In 2002, the American Cancer Society set guidelines on physical activity for cancer prevention,7 as did theWorldCancer Research Fund and the American Institute for Cancer Research in 2007.3 These guidelines have been updated since,4 and the current recommendations translate roughly into 10 metabolic equivalent task (MET)-hoursperweek,which is the equivalent towalking at anaveragepace for approximately 3.3 hours per week. These recommendationshavebroughtattention to the link between physical activity and cancer risk. However, the recommendations themselves are not finely detailed, and questions remain about the type, dose, duration, and intensity of physical activity needed to meaningfully affect risk of specific cancers. Studies suggest that colon, breast, and endometrial cancers may be the most affected by physical activity.3 However, ithasbeendifficultor impossible tocompare therelative risks associated with physical activity for cancers at differentanatomical sitesbecauseeachstudyusesdifferentpopulations andmethodsof ascertaining exposures andoutcomes. In this issueofJAMAOncology,Keumetal8 reportonphysical activity and digestive system cancer risk using data from more than43000menwhoparticipated in theHealth Professionals Study over a period of more than 26 years. They estimated the association between total physical activity asmeasured by self-reported leisure time activities and all cancers of the digestive system. The findings are provocative. For all digestive system cancers, they estimated a 26% reduction in risk (HR, 0.74; 95% CI, 0.59-0.93), comparing their high total physical activity group (≥63MET-hours/wk or 21 hours/wk of walking at an average pace [average of 3 hours/d]) vs the reference group of 8.9 MET-hours/wk or less (≤126 min/wk of walking at an average pace [average of 18 min/d]). Inanalysesstratifiedby location inthedigestivesystem,the results were especially pronounced in the upper (mouth and pharynxtosmall intestine)andlower(colonandrectum)regions of thedigestive tract,withnoassociationsobserved for cancers of thedigestive accessoryorgans (pancreas, liver, gallbladder). The association between physical activity and upper digestive tractcancerswasindependentofbodymass index(BMI)andhistory of diabetes, among ahost of other confounders. The associationwithcolorectalcancer,however,wasnotstatisticallysignificant after adjustment for BMI and diabetes. There was no addedbenefit ofweight lifting (theonly formof strength trainingexerciseassessed) inadditiontoaerobicphysicalactivity (eg, walking, jogging,running)onoveralldigestivesystemcancerrisk. Related article page 1146 Editorial Opinion