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1. SAMPLE COLLECTION: NORMAL COLORECTAL MUCOSA FROM ENDOSCOPIC PROCEDURES AT THE JOHN RADCLIFFE HOSPITAL. - PATIENTS GIVEN INFORMED CONSENT COLLECTED 10ML BLOOD AND/OR COLORECTAL BIOPSIES BIOPSIES FRESHLY USED TO EXTRACT DNA + RNA REMAINING TISSUE SNAP FROZEN 2. ASSAY OPTIMIZATION: BLOOD - NUCLEATED CELL SEPARATION - DNA EXTRACTION AND QC - RNA EXTRACTION AND QC COLORECTAL BIOPSIES - TISSUE FRAGMENTATION & HOMOGENISATION - DNA EXTRACTION AND QC - RNA EXTRACTION AND QC DNA RNA - EXTRACTION AND QC - EXTRACTION AND QC - 23 RISK SNPS POLYGENIC - RETROTRANSCRIPTION AND DNASE RISK SCORE(PRS) TREATMENT - TELOMERE LENGTH (TL) - PATHWAY EXPRESSION ANALYSIS (PEA) 3. BOWEL ASSAYS & CRC RISK: COMPARED LEVELS OF 3 ASSAYS IN A GROUP OF HEALTHY CONTROLS VS. PATIENTS WITH POLYPS/CRC - 2-STAGE DESIGN: PILOT50 (50 CASES & 50 CONTROLS) PHASE2 (182 CASES & 57 CONTROLS) - CASES SHOWED LONGER TL THAN CONTROLS (OR=1.106; P=0.025) - CASES PRESENTED WITH HIGHER NUMBER OF RISK ALLELES (P=0.007; OR=1.086) 4. BLOOD ASSAYS: ANALYZE CORRELATION BETWEEN BOWEL MARKERS AND THEIR BLOOD COUNTERPARTS - BLOOD TL WAS SIGNIFICANTLY CORRELATED WITH BOWEL TL - BLOOD TL COULD BE USED AS A PROXY FOR RISK ASSESSMENT IN A QUICK AND LESS INVASIVE WAY