Nutrition and Physical Activity Cancer Prevention Guideline Adherence and Association with Circulating Concentrations of Vitamin D and Precancerous Lesions

Abstract

Background: Many studies have reported that adherence to health promotion guidelines for diet, physical activity, and maintenance of healthy body weight may decrease cancer incidence and mortality, including site-specific cancers such as colorectal cancer. To date, there have been no studies investigating adherence to the American Cancer Society's (ACS) Nutrition and Physical Activity Cancer Prevention Guidelines and the development and characteristics of premalignant lesions. Several individual lifestyle factors targeted by the ACS guidelines have also been associated with circulating concentrations of vitamin D metabolites. These associations suggest that adherence to the ACS guidelines may be related to improved vitamin D status. This dissertation sought to 1) synthesize the evidence from published prospective cohort studies regarding adherence to the ACS and World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) nutrition and physical activity cancer prevention guidelines and the risk of overall cancer incidence and/or cancer mortality and 2) to further explore the role of adhering to a healthy lifestyle pattern as outlined by the ACS guidelines on a) colorectal adenoma occurrence and b) circulating concentrations of vitamin D metabolites using secondary data analyses from completed large prevention trials. Methods: A systematic review was performed to examine associations between adherence to established cancer prevention guidelines for diet and physical activity and overall cancer incidence and mortality. PubMed, Google Scholar, and Cochrane Reviews databases were searched following the current recommendations of Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Cross-sectional and prospective analyses of pooled participants were also conducted from the Wheat Bran Fiber (n=503) and Ursodeoxycholic Acid (n=854) trials. A cumulative adherence score was constructed using baseline data regarding body size, diet, physical activity, and alcohol consumption. Continuous vitamin D metabolite concentrations and clinically significant vitamin D categories were evaluated with adherence score category using multiple linear and logistic regression models, respectively. Baseline adenoma characteristics and new colorectal adenomas were evaluated by adherence score category using multivariate logistic regression models. Results: Twelve studies met inclusion criteria for the systematic review. High versus low adherence to established nutrition and physical activity cancer prevention guidelines was consistently and significantly associated with decreases of 10-61% in overall cancer incidence and mortality. Consistent significant reductions were also shown for breast cancer incidence (19-60%), endometrial cancer incidence (23-60%), and colorectal cancer incidence in both men and women (27-52%). Findings for lung cancer incidence were equivocal and no significant relationships were found between adherence and ovarian or prostate cancer. In the pooled analyses, concentrations of circulating 25-hydroxycholecalciferol [25(OH)D] were statistically significantly higher among participants with high versus low adherence to guidelines (31.4 ± 0.8 and 26.3 ± 0.8 ng/ml, respectively; p<0.001). For 1,25(OH)₂D concentrations, high adherence was again significantly related to greater metabolite levels, with mean concentrations of 36.4 ± 1.1 and 31.2 ± 1.2 pg/mL for high- and low-adherers, respectively (p<0.001). Furthermore, the odds of attaining sufficient 25(OH)D status were 4.30 times higher for those most adherent versus those least adherent (95% CI: 2.43-7.60). Significantly reduced odds of having three or more adenomas at baseline were shown for moderate (odds ratio [OR]=0.67, 95% confidence intervals [CI]: 0.46-0.99) and highly adherent (OR=0.50, 95% CI: 0.31-0.81) participants compared to those with low adherence (p-trend=0.005). Conversely, guideline adherence was not associated with the development of a new colorectal adenoma (moderate adherence OR=1.16, 95% CI: 0.85-1.59, high adherence OR=1.23, 95% CI: 0.85-1.79). Conclusion: From the systematic review, greater adherence to cancer prevention guidelines for diet and physical activity was consistently associated with lower risks of overall cancer incidence and mortality, including for some site-specific cancers. In addition, adherence to the ACS guidelines was associated with higher concentrations of both of 25(OH)D and 1,25(OH)₂D. Following the ACS guidelines could potentially increase 25(OH)D levels as much as that observed by a supplement of 1000 IU/d in a population similar to ours, and therefore may be a viable strategy for increasing both 25(OH)D and 1,25(OH)₂D concentrations. Further, our findings suggest that following the ACS Nutrition and Physical Activity guidelines may lead to a lower odds of multiple adenomas when at least one adenoma is detected. Finally, these guidelines and recommendations are consistent with strategies for the prevention of major diseases, and if followed, will ultimately lead to healthier lives overall.