Modifiable lifestyles factors such as obesity and physical activity play a clear independent role in the aetiology of cancer, based on mounting epidemiological evidence. However, cancer research has lagged behind other major chronic conditions as disease risk modification between body fatness and physical activity has been noted in the context of mortality and cardiometabolic outcomes. In those studies, increased risk usually conferred by a high body fatness may be attenuated or even eliminated by high levels of physical activity or fitness. This phenomenon described as “fat but fit” hypothesis has barely been evaluated in the cancer field. Given the negative impact of obesity on the burden of cancer, the examination of a possible interaction between body fatness and physical activity is of public health significance to understand cancer risk. Therefore, this thesis examined the independent and interactive (“fat but fit”) effects of body mass and physical activity or fitness on the risk of different types of cancer in multiple epidemiological studies. The interrelation between body mass and physical activity or fitness was methodologically assessed by appraising the interaction term between these two lifestyle factors in epidemiological studies used in this thesis.
There was variability in the results of the independent effects of obesity and physical activity across the studies of this thesis. Overall, obesity had a positive association with new cases of colorectal cancer, in particular colon cancer and any cancer combined among both sexes, prostate cancer in men and breast or uterine cancer in women. Conversely, physical activity or fitness had an inverse association with all-cancer sites combined or colon cancer amongst men and women; breast, uterine or lung cancer in females and with the incidence and mortality of respiratory and thoracic cancers in males. When evaluating the “fat but fit” hypothesis, there was no evidence of interaction between body mass and different levels of physical activity or fitness on many cancer outcomes. Thus, “fat but fit” might not be relevant to cancer risk. Obesity-related cancer risks appear not to be offset or eliminated by high levels of physical activity or fitness. Therefore, both a healthy body weight in addition to recommended levels of physical activity need to be promoted to impact the risk of cancer.