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

Hum Mutat. 1994;3(2):121-5. doi: 10.1002/humu.1380030206.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / epidemiology*
  • Adenomatous Polyposis Coli / genetics
  • Aged
  • Chromosomes, Human, Pair 5
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • Denmark / epidemiology
  • Female
  • Fertility
  • Gene Frequency
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Registries