Familial adenomatous polyposis (FAP): Frequency, penetrance, and mutation rate

Abstract

The nationwide Danish polyposis register includes all known Danish cases of familial adenomatous polyposis (FAP) and their relatives. By identifying all FAP patients born between 1920 and 1949, we found the frequency of the disease to be 1 in 13,528. By comparing the number of affected and nonaffected offspring born to affected parents during the same period we found the penetrance of the disease for inherited cases to be close to 100% at the age of 40 years. The mutation rate found by the direct method was 9 mutations per million gametes per generation and the proportion of new mutants was estimated to 25%. Fitness for patients between 15 and 29 years was found close to one, while for patients older than 30 the fitness was reduced, but increasing during the three decades (from 0.44 to 0.71) probably because treatment became more widespread and efficient. As we have used the overall fitness in the period, 0.87, to estimate the mutation rate by the indirect method, we found a lower value than by the direct method, namely 5 mutations per million gametes per generation.

APCgermline mutations identified in Czech patients with familial adenomatous polyposis

“…22 without FAP family history. Thus this alteration is likely to be a de novo mutation because up to 20 -25% of FAP cases are considered to be de novo mutations (Bisgaard et al, 1994).…”

An Overview of Autosomal Dominant Tumour Syndromes with Prominent Features in the Oral and Maxillofacial Region

“…The penetrance of FAP and MEN2B is near complete [94,102]. In contrast, hyperparathyroidism-jaw tumour syndrome has a low penetrance in at least some cohorts [103,104].…”

Colon Cancer Prevention by Detection of APC Gene Mutation in a Family with Attenuated Familial Adenomatous Polyposis

“…The APC gene encodes a multi-domain protein that plays a major role in tumor suppression by antagonizing the carcinogenesis pathway and also has a role in cell migration, adhesion, chromosome segregation, spindle assembly, apoptosis, and neuronal differentiation (Hanson and Miller, 2005). Mutation of APC gene presents as an autosomal dominant disease and the penetration rate of inherited cases is close to 100% at the age of 40 years (Bisgaard et al, 1994).…”