Genotype-phenotype correlations as a guide in the management of familial adenomatous polyposis

Clin Gastroenterol Hepatol. 2007 Mar;5(3):374-8. doi: 10.1016/j.cgh.2006.12.014.


Background & aims: The options for prevention of colorectal cancer in familial adenomatous polyposis are either a colectomy with ileorectal anastomosis (IRA) or a total proctocolectomy with ileal pouch-anal anastomosis (IPAA). Rectal cancer risk is eliminated by IPAA, but complication rate is higher than in IRA. Mutation analysis might predict severity of polyposis and be helpful in the surgical decision.

Methods: Patients from the Dutch Polyposis Registry with an IRA were subdivided according to the site of adenomatous polyposis coli gene mutation into the attenuated (1), intermediate (2), and severe (3) genotype groups. Cumulative risks of secondary rectal excision and rectal cancer were calculated for each group.

Results: A total of 174 patients underwent an IRA: 26 patients from group 1, 121 from group 2, and 27 from group 3. Cumulative risks of rectal cancer 15 years after surgery were 6%, 3%, and 8% in groups 1, 2, and 3, respectively. Cumulative risks of rectal excision 20 years after IRA were 10%, 43%, and 74%, respectively. The risk of rectal excision was significantly higher in group 3 than in the other groups (P < .05).

Conclusions: The risk of secondary rectal excision after IRA can be predicted on the basis of the adenomatous polyposis coli mutation site. An IRA appears to be the appropriate treatment in patients with the attenuated genotype. Patients with a severe genotype are good candidates for an IPAA.

Publication types

  • Comparative Study

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / mortality
  • Adenomatous Polyposis Coli / pathology
  • Adenomatous Polyposis Coli / surgery*
  • Adolescent
  • Adult
  • Aged
  • Biopsy, Needle
  • Child
  • Colectomy / methods
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / prevention & control*
  • Female
  • Genes, APC
  • Genetic Predisposition to Disease / epidemiology*
  • Genotype
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Mutation*
  • Neoplasm Staging
  • Phenotype
  • Predictive Value of Tests
  • Probability
  • Proctocolectomy, Restorative / methods
  • Sensitivity and Specificity
  • Survival Analysis
  • Treatment Outcome