LIFETIME RISK OF DIFFERENT CANCERS IN HEREDITARY NONPOLYPOSIS COLORECTAL-CANCER (HNPCC) SYNDROME

Identification of hereditary non-polyposis colorectal cancer (HNPCC) i ndicates theoretical life-time risks of 50% for the descendants of an affected family member and of 100% for the true gene carriers. However , besides colorectal cancer (CRC), many other cancer types and sites a re also involved, which gives reason to evaluate the magnitude of risk for various other cancer types. A detailed pedigree analysis of 40 fa milies with HNPCC identified 414 patients affected with cancer. A Kapl an-Meier life-table analysis for the cumulative risk of various cancer s was performed on the basis of the 293 putative gene carriers who had adequate clinical and histological documentation of their tumors. Cum ulative risks were highest for colorectal (78%) and endometrial cancer s (43%, women only), followed by gastric, biliary tract, urinary tract and ovarian cancers (19-9%). For the other probably HNPCC-related can cer types, such as small bower carcinoma and brain tumors, the life-ti me risk was only 1%. The risk of any metachronous cancer reached 90% a fter treatment of CRC and 75% after endometrial cancer; the second tum or was most often a new CRC or endometrial cancer. CRC remains the mos t important cancer type in the HNPCC syndrome but does not develop in all gene carriers. This makes the decision of possible prophylactic co lectomy for test-detected gene carriers difficult. Of the many other c ancer types involved, at least endometrial cancer is common enough to necessitate a specific surveillance program. (C) 1995 Wiley-Liss, Inc.