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


CONCLUSIONS
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.
Nieuwenhuis
Marry H
MH
The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands. m.nieuwenhuis.stoet.nl
Bülow
Steffen
S
Björk
Jan
J
Järvinen
Heikki J
HJ
Bülow
Charlotte
C
Bisgaard
Marie Luise
ML
Vasen
Hans F A
HF
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000473:pathology* / Q000601:surgery; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D015331:Cohort Studies; D003082:Colectomy; D005060:Europe; D017491:Genes, APC; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D012004:Rectal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012086:Reoperation; D012189:Retrospective Studies; D018570:Risk Assessment; D055815:Young Adult