ROLE OF CLINICAL-CRITERIA IN THE DIAGNOSIS OF HEREDITARY NONPOLYPOSISCOLORECTAL-CANCER (HNPCC) - RESULTS OF A MULTIVARIATE-ANALYSIS

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dom inant disease characterized by early-onset colorectal tumors, primaril y in the right colon, that are frequently associated with other cancer s. In the absence of a reliable biomarker, clinical criteria for diagn osing HNPCC have been proposed by the international collaborative grou p on HNPCC (ICG-HNPCC). However, these criteria are often too restrict ive for application in small families. We analyzed 6 clinical/patholog ical features suggestive of genetic colon-cancer risk in 970 colorecta l-cancer patients defined according to the ICG criteria as HNPCC (96) or non-HNPCC (874). Logistic regression analysis was used to determine their relative potentials for predicting the diagnosis of HNPCC. The most predictive were then used to estimate HNPCC risk levels within th e non-HNPCC group. Multivariate analysis showed the following associat ions with HNPCC diagnosis: vertically transmitted cancer (''highly pre dictive''), early-onset (<50 years) colorectal cancer, aggregation of tumors in the nuclear pedigree and proximal-colon tumors (the last 3 c onsidered ''predictive''). Re-evaluation of all families revealed that 76 non-HNPCC families (8.9% of the whole series) satisfied our highly predictive vertical-transmission criterion plus at least one of the o ther ''predictive'' criteria. The presence of 2 consecutive generation s affected by colorectal cancer or early primaries seems to be a major risk indicator of hereditary colorectal cancer. Using this approach w e identified a large group of families that require further evaluation , although they do not currently meet the ICG-HNPCC criteria for HNPCC . (C) 1994 Wiley-Liss, Inc.