Attenuated familial adenomatous polyposis manifests as autosomal dominant late-onset colorectal cancer

Eur J Hum Genet. 2014 Nov;22(11):1330-3. doi: 10.1038/ejhg.2014.20. Epub 2014 Feb 19.

Abstract

Colorectal cancer (CRC) risk is well defined for families of patients with classical familial adenomatous polyposis (FAP). However, the risk for those with an attenuated form of FAP is less well characterised. In this study, we estimated CRC risks for carriers of a novel germline mutation in the APC gene that causes attenuated FAP (AFAP). We performed genetic testing on 53 individuals from seven AFAP families harbouring an identical APC:c.288T>A mutation. Using a modified segregation analysis, we estimated relative and absolute CRC risks for mutation carriers. Twenty-three individuals harboured the disease causing mutation. CRC occurred in 28 individuals (mean 61.7 years, range 32-80 years). The estimated CRC relative risks for mutation carriers aged 60-69 and ≥70 years were 19 (95% CI: 1.77-204.08) and 45 (95% CI: 11.32-180.10), respectively, while the absolute CRC lifetime risk for men was 94% (95% CI: 67.5-99.9%), and for women, 84% (95% CI: 50.9-99.0%). This study shows that AFAP can manifest as autosomal dominant late-onset CRC. These findings highlight a subgroup of inherited CRCs that require new criteria for identification and surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenomatous Polyposis Coli / complications
  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli Protein / genetics
  • Adenomatous Polyposis Coli Protein / metabolism
  • Adult
  • Aged
  • Colorectal Neoplasms / complications
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / genetics*
  • Exons
  • Female
  • Genetic Testing
  • Germ-Line Mutation
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Risk Factors
  • Young Adult

Substances

  • APC protein, human
  • Adenomatous Polyposis Coli Protein

Supplementary concepts

  • Attenuated familial adenomatous polyposis