Novel genetic and epigenetic alterations in ... - Ous-research.no

IntroductionFigure 6. Incidence rate for colorectal cancer compared with other types of cancer and age.a) Age-adjusted incidence rate for CRC compared to cancer in general in a Norwegian population. b) Theincidence of CRC is plotted against age at diagnosis. Raw data was obtained from the Norwegian CancerRegistry – Cancer in Norway 2006.The majority (70%) of CRC occurs sporadically, and only ~5% of all registered CRC are dueto single hereditary components, such as Lynch syndrome (OMIM #120435), formerlyknown as hereditary non-polyposis colorectal cancer (HNPCC), and familial adenomatouspolyposis (FAP, OMIM #175100). The remaining ~25% of CRC account for families withan accumulation of cancer, but with no known clear-cut Mendelian inheritance[55], and maybe multifactorial. Some studies claim that the fraction of heritable CRCs are as much as35%[56].Both Lynch syndrome and FAP are autosomal dominant disorders with a relative life-timerisk of developing CRC of 80% and 100%, respectively[57]. Lynch syndrome is caused by agerm line mutation in one of the components of the DNA mismatch repair system (MMR),most commonly MSH2 or MLH1[14] (see page 28-30 for MMR details). FAP is caused bygerm line mutation in the APC gene, a central cytoplasmic complex involved in degradationof -catenin (CTNNB1) in the WNT signaling pathway.22