Inherited multitumoral syndromes including colorectal carcinoma

Inherited multitumoral syndromes including colorectal carcinoma are the followings: familial adenomatous polyposis (FAP), hereditary non-polyposis colon cancer (HNPCC) and Peutz-Jeghers syndrome (PJS). The studies of genotype-phenotype correlation have shown that various types of colonic polyposis are related with germline mutation of adenomatous polyposis coli (APC) gene, that is also responsible for a wide number of extracolonic manifestations. Concerning severity of polyposis, it has been suggested to perform ileorectal anastomosis in patients with intermediate FAP, whereas it has been suggested to remove the rectum from the beginning and to perform ileopouch anastomosis in patients with severe FAP (germline APC mutations between codons 1250 and 1464, i.e. mutation cluster region-MCR). Concerning extracolonic manifestations, original studies from our laboratory have shown that three peculiar, even if unusual extracolonic manifestations of FAP, were in the 5′ portion of the gene, but almost always outside of MCR. In particular, in some patients or in some kindreds all these manifestations may be present together. It is suggested, from one hand, because of the wide variety of genotype-phenotype correlation word of caution before selecting surgical treatment simply on the basis of the germline mutations, on the other hand co-segregation of some extracolonic manifestations could facilitate intensive screening, early diagnosis and optimal time for treatment.