We found that obesity and inactivity were associated with poorer overall and disease specific survival in patients diagnosed with CRC. The associations were more compelling for obesity, specifically waist circumference, per cent body fat, and weight than for exercise. In particular, those participants with an “action level” waist circumference had a 35% reduction in disease specific survival compared with those with a “healthy” waist circumference. No effect on survival was seen for BMI or regular walking. Our study found that exercisers, compared with non‐exercisers, had an absolute improvement in five year overall survival of 14% (12% for disease specific survival), a result that is clinically relevant. The beneficial effects of exercise were confined to cases with stage II or III tumours at diagnosis, with exercise resulting in a 39% reduction in all cause mortality and a 51% reduction in disease specific mortality within this subgroup. This improvement in survival is at least as large as is achieved with adjuvant chemotherapy.16,17
One of the strengths of our study relates to the accuracy of our body size measurements. Each case had precise measurements taken by trained staff rather than self reporting of height and weight. In addition, we had near complete data on the tumour characteristics and treatments received for our cases and identification of all deaths that occurred within the follow up period. It could be argued that more aggressive tumours might impact on a person's ability to regularly exercise by causing lethargy or pain and in so doing favorably bias the survival of exercisers. Similarly, weight can certainly be affected by an underlying malignancy. In order to exclude the possibility that undiagnosed (but possibly symptomatic) cancers could have influenced exercise patterns or body size and potentially bias the findings, we performed our analyses excluding cases diagnosed within two years of enrolment into the cohort study. The associations between exercise, adiposity, and survival were unaltered after we excluded these cases.
The main weakness in our study relates to the accuracy of the exercise measurement. This was self reported and we have no data on the duration of an individual's activity habits. Nor can we make any comment on the length of time an individual exercised per week. However, any biases introduced by this would most likely attenuate the associations. Because only a small proportion of cases reported “regular vigorous” exercise, we are unable to say whether the vigorousness of exercise is important. Similarly, our study is not powered to demonstrate an association between the frequency of exercise and survival.
Another potential criticism of our study could be that our measurement of physical activity and body size predated the diagnosis of CRC. We did not assess whether exercise habits were maintained during the period of follow up nor was body size and shape reassessed after cancer diagnosis. Thus it is not clear whether weight loss or exercise following detection of CRC would influence the outcome. It is well established that CRC development occurs over many years and involves multiple genetic mutations,18
and our findings suggest that exercise and adiposity may influence this process in its early stages. Our findings are also consistent with prospective cohort studies that have shown exercise (in the premorbid period) reduced the risk of developing colon cancer,19,20,21,22,23,24,25
as well as cohort studies that demonstrated an increased incidence of colon cancer with rising waist circumference, particularly in men.20,26,27,28
At first inspection, our findings of improved survival with regular exercise and reduced adiposity may seem obvious due to the well known health advantages of exercise and weight loss in reducing cardiovascular mortality. However, there were only 27 deaths (13% of all deaths) not attributable to CRC (14 occurring in non‐exercisers and 13 in exercisers) while 181 deaths were due to CRC. If our findings of improved survival were due to reductions in non‐CRC deaths (such as deaths due to heart disease, stroke, or diabetes) one would expect to see less of an effect on disease specific survival compared with overall survival. In contrast, we found the associations between survival and both regular exercise and low adiposity to be, if anything, larger for disease specific survival than overall survival (table 3). This suggests that the improved survival seen was a result of a direct effect on tumour biology.
With respect to premorbid body size measurements, the strongest effects were seen with per cent body fat and waist circumference. For every 10% increase in body fat we found a 33% decrease in disease specific survival, while a 10 cm increase in waist circumference resulted in a 20% reduction in disease specific survival. Slightly weaker reductions were observed for overall survival. The probability of survival did not appear to vary by measures of BMI, as has been found by others,7,8
or fat free mass. As BMI can be elevated by an increase in muscle bulk rather than body fat, this suggests that a more accurate measure of adiposity, and in particular central adiposity, is more important for determining survival from CRC than BMI. The hypothesis that waist circumference may be a more important indicator than BMI is consistent with our previous work that investigated the incidence of colon cancer in men.27
Whether or not the detrimental effects of being overweight or the beneficial effects of regular exercise differ by the site of the primary tumour is not clear from our study although some trends were observed (table 4). It is well known that the molecular characteristics of CRCs vary, and tumours arising in the right colon differ in this respect to either left colon or rectal cancers, a classic example being the prevalence of microsatellite instability.29
Even though the effects of exercise and obesity were independent, it is likely however that the mechanisms involved are similar. If this were so, obesity and a sedentary lifestyle should both negatively impact on survival for tumours originating in the same locations, a finding not supported by our study. Although there are many studies demonstrating a reduced risk of developing colon cancer in more physically active people, this has not been shown for rectal cancer. We found no effect of exercise on survival for rectal cancer.
In conclusion, we have observed improved survival for patients with CRC who participated in regular exercise prior to diagnosis. This effect was stronger for right sided colon cancers, and stage II–III disease. We have also observed a detrimental effect on disease specific survival associated with increased adiposity prior to diagnosis, this effect being greatest for cancers distal to the splenic flexure and independent of exercise. Although the precise mechanisms are unknown, should the veracity of these observations be confirmed, maintenance of ideal body weight and promotion of physical activity could form the basis of interventions to reduce not only the incidence of CRC but also mortality. Such interventions are also likely to have beneficial effects on cardiovascular disease and metabolic disorders such as type II diabetes.