and FAP are both associated with familial colon HNPCC和FAP都与家族性结肠癌相关课件.ppt

HNPCC and FAP are both associated with familial colon cancer but differ in many aspects. Describe the similarities and differences between these conditions. How does MYH polyposis differ from both? Helen Stuart, Cardiff Essay plan Colorectal cancer Third most common cause of cancer-related death in men and women in the western hemisphere. Among colon cancer patients, hereditary risk contributes ~20%. Ref: S Narayan and D Roy Molecular Cancer 2003, 2:41? 2 major forms of hereditary colorectal cancer are: Hereditary non-polyposis colorectal cancer (HNPCC) [~2-7% of total colorectal cancer] Ref: A Muller and R Fishel Cancer Investigation 2002; 20(1):102-109 Familial adenomatous polyposis (FAP) Diagnosis of hereditary colorectal cancer HNPCC Lacks clear phenotypic characteristics Diagnosis based on: Family history (Amsterdam or Bethesda criteria) inc earlier age of onset than gen pop (45yrs vs 63yrs) Demonstration of defective MMR (MSI) Confirmed by identification of mutation FAP Presence of 100 adenomatous polyps and microadenomas in the large intestine. Diagnosis based on: Polyps Family history Confirmed by identification of mutation Cancer predisposition HNPCC 50-80% lifetime risk of colon cancer Proximal colon cancer Extra-colonic manifestations: Endometrium, ovarian, stomach tumours. Also: CNS tumours (Turcot), skin tumours (Muir-Torre) FAP Virtually 100% lifetime risk of colon cancer Distal colon cancer Extra-colonic manifestations: Desmoids, gastric adenomas, osteomas. Also: CNS tumours (Turcot), osseous, dental and cutaneous anomalies (Gardner) Ref: S Baglioni and M Genuardi 2004 Am J Med Gen 129C:35-43 Inheritance HNPCC Autosomal dominant inherited predisposition FAP Autosomal dominant inherited predisposition Both involve inherited germline mutation + extra somatic mutation. Tumours usually arise when a second somatic hit affects the wild-type allele. This is termed ‘loss of heterozygosity’. Knudson Two-Hit Hypothesis of Tumori