Novel Insights on Lifestyle Recommendations and Mechanisms for Colorectal Cancer Prevention

Abstract

Many modifiable risk factors have been identified for colorectal cancer (CRC), but additional research is required to synthesize these findings to create the best guidelines for prevention. Furthermore, additional work is needed to elucidate the biological mechanisms driving associations for established risk factors. First, we examined adherence to several established dietary indices created for chronic disease prevention in relation to CRC risk within the Nurses’ Health Study (NHS) and Health Professionals Follow-up Study (HPFS). Over up to 26 years of follow-up, we documented 2,690 CRC cases, and observed reduced CRC risk in men who adhered to these diets, but no evidence of reduced CRC risk for women. We noted strongest results in men for distal colon cancer risk, particularly when we considered diet in the distant past. Second, we constructed a lifestyle index based on 2018 cancer prevention recommendations provided by the World Cancer Research Fund/American Institute for Cancer Research in NHS and HPFS. These recommendations, which include diet as well as adiposity and physical activity, were strongly associated with a reduced risk of CRC in both men and women, though results were stronger in men. We considered the diet recommendations alone as well, and found inverse associations for men, but generally no associations in women. Lastly, given previously documented strong associations between adiposity and CRC risk in men, we examined how these associations are potentially mediated by inflammatory and metabolic biomarkers in a nested case-control study in HPFS. We observed mediation of metabolic biomarkers for analyses of adult weight gain and BMI with CRC risk, but no evidence of mediation by inflammatory biomarkers, or for analyses of waist circumference generally. In summary, these studies illustrate that considering modifiable risk factors for CRC via diet and lifestyle indices may be useful for CRC prevention in men, though other combinations of modifiable risk factors may need to be considered for women. Moreover, it suggests that adiposity, one of the strongest modifiable risk factors for CRC in men, may be associated with CRC risk through metabolic and insulin-related processes.