Mechanisms underlying the effects of nutrition, adiposity and physical activity on colorectal cancer risk

Lifestyle factors including diet, body fatness and physical activity modulate the risk of developing colorectal cancer (CRC) and it is estimated that over half of CRC cases in the UK are linked to such factors. This review focuses on describing the underlying mechanisms behind the effects of lifestyle factors (predominantly dietary) for which there is strong (convincing or probable) evidence for effects on CRC risk, described in the recently published World Cancer Research Fund/American Institute for Cancer Research colorectal cancer report. These include a protective effect of physical activity, wholegrains and dietary fibre, dairy products and calcium supplements, and increased risk associated with red and processed meats, alcoholic drinks and higher body fatness. The postulated mechanisms underlying the effects of lifestyle on CRC risk, including effects on inflammation, insulin resistance and the microbiome, and affecting pathways involved in the regulation of cell proliferation, differentiation, DNA repair and apoptosis are described. Epigenetic mechanisms that are dysregulated in colorectal carcinogenesis leading to aberrant patterns of DNA methylation and aberrant expression of microRNAs may also be modulated by lifestyle factors and consequently modulate CRC risk. It is likely that an interplay of these mechanisms is involved in the modulation of CRC risk as well as a combination of these lifestyle factors.