 FAP - familial adenomatous polyposis  germline mutations in the APC gene (“gatekeeper”)  HNPCC - hereditary nonpolyposis colon cancer (a.k.a. Lynch syndrome)  germline mutations in DNA mismatch repair genes (“caretaker”)

 autosomal dominant  loss of heterozygosity

 mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)  maps to human chromosome 2p22-21

 heterozygous for mismatch repair genes  hMSH2 and hMLH1 = tumor suppressors

 Black = +/+  Green = G674A / +  solid red = G674A/G674A  blue = -/-  Dotted red = backcross

 the HALMARK of Lynch Syndrome (HNPCC)  Defective MMR = MSI  5 standard DNA markers: *BAT26*

 surgical management – partial colectomy  chemotherapy – need functional MMR  possible preventative treatment › aspirin › resistant starch (fiber)