Despite increasing adherence to routine screening and advances in therapeutic strategies, colorectal cancer is still a major health problem. Colorectal cancer is the 3rd leading cause of cancer death in the US. Moreover, the incidence of this disease is projected to increase by 52% by 2030 due to the expansion of the aging population. Yet, very few colorectal neoplasia (pre-cancerous and cancerous lesion) prevention strategies are available other than routine screening. The etiology of colorectal neoplasia (CRN) is complex; however, modifiable environmental factors including diet, the gut microbiota, and inflammation, are accepted as major contributors to colorectal carcinogenesis. Accumulating evidence supports that diet is one of the most important environmental factors that modulate gut microbiota composition and the gut microbiota has been implicated in CRN development. However, the dietary patterns that promote unhealthy changes in the gut microbiota (dysbiosis) and the enrichment of CRN-promoting bacteria are still incompletely understood. A better understanding of the CRN-promoting mechanisms, including the interplay between diet and the gut microbiota, would greatly advance current knowledge and serve as a platform for future studies evaluating diet- based CRN prevention strategies via the modulation of the cancer-promoting gut bacterial populations. Most studies have concentrated on specific bacteria or on profiling gut bacterial species associated with CRN. However, the mechanisms by which gut bacteria exert their CRN-promoting effects are not fully elucidated. The main goal of the current proposal is to examine a panel of bacterial genes encoding pro- inflammatory and DNA damaging toxins that may contribute to colorectal carcinogenesis and to evaluate if these genes are associated with pre-cancerous lesions (high-risk adenomas) and specific dietary patterns. The innovative aspect of this study is that it focuses on the evaluation of specific toxin-encoding bacterial genes rather than profiling gut bacterial species. Our central hypothesis is that individuals with high-risk adenomas will have a higher prevalence of these toxic genes and that these toxins contribute to carcinogenesis by causing DNA damage and the perpetuation of inflammation. Our study aims to characterize the toxic bacterial gene profile in stool and colonic tissue and to determine if they are associated with high-risk adenomas. We will also assess if presence of the toxic bacterial genes is associated with inflammation (Aim 1). Furthermore, we will examine dietary patterns and the prevalence of these toxic genes during a 1-year period (Aim 2). The significance of this study is that it addresses a gap in scientific knowledge regarding the CRN-promoting toxic bacterial by-products produced by the gut microbiota and their association with specific dietary patterns. The data generated by this study may shed light on the gut microbiota-driven carcinogenic mechanisms and on future dietary interventions for CRN prevention aiming at reducing exposure to injurious bacterial by-products.
Colorectal cancer is potentially preventable, but it is still one of the leading causes of cancer death with few prevention strategies available other than routine screening. The current proposal aims to explore if changes in the prevalence of a panel of genes encoding genotoxic and/or pro-inflammatory bacterial toxins in stool and colonic tissue is associated with colorectal cancer precursor lesions (high-risk colorectal adenomas) and if dietary patterns are associated with the prevalence of these toxic genes. The data generated by this study will provide evidence supporting the role of these toxins in colon carcinogenesis and may shed light on future dietary intervention studies aiming at reducing exposure to the cancer-promoting, bacterial by-products encoded by these genes as a colorectal neoplasia prevention strategy.
| Roche-Lima, Abiel; Carrasquillo-Carrión, Kelvin; Gómez-Moreno, Ramón et al. (2018) The Presence of Genotoxic and/or Pro-inflammatory Bacterial Genes in Gut Metagenomic Databases and Their Possible Link With Inflammatory Bowel Diseases. Front Genet 9:116 |
| Ramírez-Amill, Reinaldo; Soto-Salgado, Marievelisse; Vázquez-Santos, Carla et al. (2017) Assessing Colorectal Cancer Knowledge Among Puerto Rican Hispanics: Implications for Cancer Prevention and Control. J Community Health 42:1141-1147 |
