HNPCC-LYNCH-SYNDROME AND IDIOPATHIC INFLAMMATORY BOWEL-DISEASE - A HYPOTHESIS ON SHARING OF GENES

Colon cancer occurring in patients with Lynch Syndrome and in Inflamma tory Bowel Disease (IBD) share many features. There is some evidence t o support the assumption that multiple genetic factors play an importa nt role in the pathogenesis of idiopathic IBD and Lynch Syndrome. In o ur previous study, providing detailed medical, genetic and pathologic findings on 202 hereditary non polyposis colorectal cancer (HNPCC) rel atives we found in the colonic mucosa features indicating an IBD thoug h all the screened subjects of the family denied symptoms of IBD. Some studies have reported that the rate of undetected IBD ranges from 27 to 38%. Finally, a member of this family, considered not at risk for c ancer by genetic analysis results, developed a clinically manifested I BD. The morphological aspects of the disease were not discussed in our previous study. It is possible that many members of this family inher it a major gene giving liability to the disease and are carriers of a subclinical form of IBD with a minimal morphological marker which beco mes manifest in some members when other factors intervene. A possible genetic model linking the two diseases can be suggested: IBD needs two major genes for susceptibility (s) and clinical development (D). Both can be present in IBD and Lynch Syndrome, but in the latter a third g ene plays a suppressor role on the development gene (D). In conclusion we hypothesize that the IBD developing gene may be considered as prot ective against HNPCC, and this condition may result in a selective gen etic advantage.