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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Identification of hereditary nonpolyposis colorectal cancer in the general population. The 6-year experience of a population-based registry.

BACKGROUND. Hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) is an autosomal dominant disease characterized by early-onset intestinal neoplasms, localization of tumors in the proximal colon, and frequent association with cancers at other sites, especially the endometrium, skin, and stomach. The identification of HNPCC is often difficult, owing to the lack of biomarkers and the extreme frequency of sporadic colorectal cancer in the Western World. METHODS. The authors reviewed the clinical data and the family trees of all patients (n = 817) with colorectal malignancies registered in the local health district between 1984-1989 with the following objectives: (1) to identify families with HNPCC and (2) to establish the frequency of the syndrome in northern Italy. Six clinical criteria were defined (vertical transmission, familial aggregation, early age at onset, right colon localization, multiple tumors, and mucinous carcinoma), all indicative of an increased possibility of HNPCC. RESULTS. The registered families were divided into various subgroups according to the presence (in the nuclear pedigree) of four or more criteria (41 families, 5.0% of total), three criteria (58 families, 7%), two criteria (73, 8.9%), or less than two criteria (203 families, 24.8%). The remaining 380 case families did not show criteria suggesting a genetic component. One hundred thirty-three genealogic trees were extended further to gather information on second-degree and third-degree relatives. The expanded pedigrees were further analyzed to ascertain if they met the recently proposed requisites for HNPCC. Nineteen of 37 (51%) families with four criteria met the minimum requisites and could therefore be considered HNPCC. Similarly, HNPCC was diagnosed in six extended pedigrees of the three-criteria (16.6%) and in three families (8.5%) of the two-criteria subgroups. The difference in the detection of HNPCC among various subgroups was statistically significant (P < 0.001). From the observed findings, the frequency of HNPCC in this population can be estimated to be between 3.4-4.5% of all cases of colorectal cancer. CONCLUSIONS. HNPCC can be identified in the general population through the data of a colorectal cancer registry if the nuclear pedigrees of all incident cases are traced and a proportion of them selectively expanded. The observed frequency of HNPCC was rather consistent with previous estimates in other populations.[1]

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