Familial aggregation in multiplex families with CNS cancers was mainly attributed to neurofibromatosis and in colorectal cancer to FAP- and HNPCC-syndromes.
We performed whole-genome sequencing of 61 Romanian CRC cases with a family history of cancer and/or early onset of disease, focusing the analysis on candidate variants in the LS and FAP genes.
Thus, a family with features of the Lynch syndrome will merit microsatellite instability testing, consideration for immunohistochemistry evaluation, and mismatch repair gene testing, while, in contrast, a patient with FAP will require APC testing.
We also summarize the differences between FAP, AFAP, and HNPCC; extend the graphic description of the MSI mechanism; and propose a diagnostic strategy for HNPCC.
In FAP and HNPCC patients, the 5'-cytosine DNA methyltransferase mRNA levels of adenomas were significantly higher (P<0.05) than of flat mucosa in the same group, but both showed great variability from patient to patient.
These are important, both in inherited syndromes (familial adenomatous polyposis [FAP] and hereditary nonpolyposis colorectal cancer [HNPCC], respectively) and in sporadic cancers.Other less well defined pathways exist.
The age distribution at diagnosis of sporadic patients was significantly higher than that of FAP and HNPCC patients (median 60 years vs. 43 and 49 years; p < 0.0001).