Molecular Colonoscopy & Multi-omics.

We will implement molecular colonoscopy, a cutting edge molecular risk assessment tool, for estimating the risk of healthy-appearing individuals for colorectal neoplasia. Using this tool, we will identify biomarkers predicting the relative probability of each individual for colorectal neoplasias. In parallel, we will implement established translational protocols using Drosophila to pinpoint dietary, drug and microbial interventions that may affect regenerative inflammation, DNA damage and tumorigenesis. We will also use Drosophila for quick functional genetics and metagenomics to assess the “treatability” of novel identified biomarkers of risk for colon cancer. Finally, we are establishing an infrastructure aiming to corroborate molecular colonoscopy as a service to the community so that the frequency of colonoscopies is ultimately customized and dietary/probiotic interventions are recommended specifically to each individual. Our service will be continuously refined and validated with the increasing number of humans analyzed and the access of local and international public and private medical health care bodies to our infrastructure (Figure). Cohort, cross sectional, and case-control studies are collectively referred to as observational studies. We are starting our analysis with a cross sectional study to determine prevalence of cancer-prone neoplasias in a group of 500 randomly selected individuals. At the same time we will select 32 CRC-prone and 64 histologically-healthy individuals in a case-control study to identify possible biomarkers of risk for neoplasias. This primary analysis is relatively quick and easy, but doesn’t permit distinction between cause and effect. It is essential though for pinpointing candidate biomarkers of risk for neoplasias, which will be further validated in a nested cohort study determining colonic neoplasia incidence among biomarker positive vs. negative individuals. Because biomarker measurements in our cohort study will precede neoplasia incidence they may distinguish between cause and effect. Following these studies and in combination with translational studies of causality using Drosophila and mice it will become ethically acceptable to perform clinical trials including probiotic, dietary and pharmaceutical interventions against colon cancer.