Abstract SY17-03: Can a change in diet change your cancer risk

There is a remarkable variation in gastrointestinal cancer risks around the world, best illustrated by colon cancer, where the incidence varies 20-fold between Westernized and less-developed countries. Overwhelming experimental and human study evidence shows that the variation can be accounted for by environmental factors rather than genetic constitution. For example, studies have shown that migration from a low-incidence country to a high-incidence country results in a change in risk to that of the host country within one generation. This is insufficient time for genetic mutation to account for the change. Less than 10% of cancers are due to inherited genetic aberrations, and GWAS studies have struggled to identify mutations that strongly influence risk for developing sporadic colon cancer. On the other hand, there is convincing evidence, based on observational and intervention studies, that risk of colon cancer is increased by consumption of meat and processed meats but suppressed by the consumption of fiber-rich foods, suggesting that the primary environmental factor that drives risk is what we eat. Recent studies of ours in African Americans, who suffer the highest rates of colon cancer incidence and death in the U.S., showed that a change to a traditional "African" high-fiber (55 gm/day), low-meat diet suppressed mucosal biomarkers of colon cancer risk in their colons within 2 weeks (1). Furthermore, these biomarkers were increased when rural Africans were given a "Western" diet for only 2 weeks. We obtained evidence that these benefits were mediated by the colonic microbiota, which break down undigested food into metabolites that either support mucosal health and are antineoplastic, for example short-chain fatty acids such as butyrate, or are inflammatory and carcinogenic, such as conjugated bile acids (which increase in a high-fat diet) and nitroso-compounds (which increase with a high-meat diet). Butyrate has a remarkable array of colonic health-promoting and antineoplastic properties: It is the preferred energy source for colonocytes, it maintains mucosal integrity, and it suppresses inflammation and carcinogenesis through effects on immunity, gene expression, and epigenetic modulation (2). There is experimental and epidemiologic evidence that the current recommended fiber intakes proposed by the U.S. Department of Agriculture of 22 gm/day for women and 38 gm/day for men, which were formulated to support cardiovascular health, are insufficient to prevent colon cancer. Our results suggest that the quantity should be closer to 50 gm/day, which is what is contained in the rural African diet; rural Africans rarely get colon cancer. This talk will discuss the mechanisms behind these diet-microbial-metabolite effects, which could be modified by diet change, to achieve the objective of preventing colorectal cancer in Western societies. References 1. Nat Comm 2015. 2. Nature Reviews 2016. Citation Format: Stephen J D O9Keefe. Can a change in diet change your cancer risk [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY17-03. doi:10.1158/1538-7445.AM2017-SY17-03