CRC: Epidemiology/risk factors CRC Epidemiology Sporadic average risk Hereditary CRC Most common GIT cancer syndromes: 3rd most common cancer Higher than average 2nd most common cancer CRC risk &include: death 2% die from this cancer. FAP Men>women AFAP Blacks>white HNPCC Increase sharply after 50 IBD Familial CRC.
Stratification of Colorectal Cancer Risk CRC Risk High riskAverage risk -ve family • FAP 100% •HNPCC 10% history •IBD 10-20% Most •Familial FDR 10% LTR 5-6% Occur earlier <50 >50 years. minority years. Text ALL
Risk/protective factors for CRC Risk factors protective factors Hereditary CRC No family H/O CRC IBD CRC Asia/Africa WESTERN High veg;fruits/ calcium/folatePhysical inactivity Physical activity High red meat, sucrose,fatLow calcium/folate. Obesity,smoking, Alcohol, cholecystectomy
Adenoma-carcinoma sequence develop over10 years: rationale for screening
Rationale for screening by colonoscopy CRC LAP with dysplasia Screening for early detection Large adenomatous polyps Small adenomatous polyps Normal30-50% of adults develop adenomatous polyps during their lifetime, but only 1 / 20will progress to cancer.15-25% >50 ys have adenomatous polyps, males>females.
Hereditary CRC Syndromes: FAP Mutation in APC genes 100% will develop 100s of adenomatous colonic polyps & cancer FAP By 40 years age. GIT Extra colonic tumors: 2nd most common after colonic;adenoma/adenocan of ampulla of vater, Fundal gland polyps.
Hereditary CRC Syndromes: FAPNeed screening colonoscopy earlier than The usual age of 50 years Extra GIT Features: Bone/soft tissue tumors FAP Retinal pigment epith hypertrophy Treatment: Total colectomy with ileostomy to prevent cancer.
Hereditary CRC Syndromes: AFAPMutations at the terminal end of the APC gene 20 or more adenoma AFAP SAME RISK OF CRC.
Hereditary CRC Syndromes: HNPCC Mutations at DNA MMR gene Polyps larger more in proximal colon HNPCC Progress more rapidly to CRC. 8O% develop cancer >50 Vs 5% > 50 in average risk persons.Extra-colonic tumors:FRS,Kid,pancbil,SI
Hereditary CRC Syndromes: familialDo not meet criteria for FAP or HNPCC 1ST degree or 2nd degree relative with CRC before or after 50 Familal CRC Risk increase with increasing numbers of Affected relatives.
Hereditary CRC Syndromes: others Familial juvenile polyposis the Peutz-Jeghers syndrome (hamartomatous polyps) othersBoth at increased risk for developing CRC.
IBD CRC riskDuration > 8 years of active colitis Early age of onset Extent IBD CRC Risk Presence of PSC.
Management Surgery is the only hope for cure. Carcinomas within 2 cm of the anal verge may require abdomin- operineal resection & colostomy. Postoperative colonoscopy after 6–12 months &periodically thereafter for local recurrence or new ‘metachronous’ lesions, occuring in 6% of cases. Adjuvant radio-chemotherapy for rectal cancer. Paliative chemo-radiotherapy or stenting for inoperable cases.