Genotype predicting phenotype in familial adenomatous polyposis: a practical application to the choice of surgery

Dis Colon Rectum. 2009 Jul;52(7):1259-63. doi: 10.1007/DCR.0b013e3181a0d33b.

Abstract

Purpose: Genetic information may help preoperatively select patients with familial adenomatous polyposis for either colectomy with ileorectal anastomosis or proctocolectomy with ileal pouch-anal anastomosis. Although complicated, the latter procedure has a low long-term risk of rectal cancer.

Methods: Data were obtained from four national polyposis registries. On the basis of previously described genotype-phenotype correlations, patients were divided into three genotype groups predicting attenuated, intermediate, and severe polyposis phenotypes. Cumulative risks of secondary proctectomy and rectal cancer after primary colectomy were calculated using the Kaplan-Meier method.

Results: Four hundred and seventy-five polyposis patients with a previous colectomy were included. Cumulative risks of secondary proctectomy 20 years after primary colectomy were 10%, 39%, and 61% in the attenuated, intermediate, and severe genotype groups, respectively (P < 0.05, groups compared separately). Cumulative risks of rectal cancer after primary colectomy were 3.7%, 9.3%, and 8.3%, respectively, in the three groups (P > 0.05, groups compared separately).

Conclusion: Mutation analysis may be used to predict the risk of secondary proctectomy after primary colectomy in familial adenomatous polyposis. Patients with severe genotypes have a high risk of reoperation after primary colectomy and will benefit from primary proctocolectomy with ileal pouch-anal anastomosis. The risk of rectal cancer after primary colectomy was not significantly different between the three groups.

Publication types

  • Multicenter Study

MeSH terms

  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology*
  • Adenomatous Polyposis Coli / surgery
  • Adolescent
  • Adult
  • Aged
  • Child
  • Cohort Studies
  • Colectomy*
  • Europe
  • Genes, APC*
  • Genotype
  • Humans
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / surgery
  • Reoperation
  • Retrospective Studies
  • Risk Assessment
  • Young Adult