Diseases of the Colon & Rectum

, Volume 44, Issue 8, pp 1090–1097 | Cite as

Relationship betweenAPC genotype, polyp distribution, and oral sulindac treatment in the colon and rectum of patients with familial adenomatous polyposis

  • Irene Guldenschuh
  • Rainer Hurlimann
  • Andreas Muller
  • Rudolf Ammann
  • Beat Mullhaupt
  • Zuzana Dobbie
  • Gian-Franco Zala
  • Renata Flury
  • Walter Seelentag
  • Jurgen Roth
  • Christa Meyenberger
  • Michael Fried
  • Thomas Hoppeler
  • Allan D. Spigelman
  • Rodney J. Scott
Original Contributions
  • 25 Downloads

Abstract

PURPOSE: Familial adenomatous polyposis is an inherited colorectal cancer syndrome characterized by the presence of multiple adenomatous colorectal polyps. Molecular studies have revealed that germline mutations in theAPC gene are the underlying cause of the disease. The nonsteroidal anti-inflammatory agent sulindac has been shown to reduce the number of colorectal adenomas. Most sulindac trials in the large bowel have focused on the distal colon and relatively little is known about its effect on the proximal colon. Moreover, it is unknown whether the site of theAPC mutation affects the efficacy of sulindac. METHODS: This study investigated whether there were regional differences in the effect of sulindac on the colon and whether response to sulindac was dependent on the site of mutation in theAPC gene. In an open prospective study 17 patients with familial adenomatous polyposis were treated with 300 mg oral sulindac daily for four months followed by a washout phase of six months. Ten of the patients had an intact colon and seven had rectal stumps only. The number, size, and the degree of dysplasia of the adenomas were evaluated by colonoscopy at entry, end of treatment and end of the study. RESULTS: Overall, a statistically significant decrease in the number of adenomas was observed (120±112 to 28±64,P=0.007). After cessation of sulindac treatment the number of adenomas increased to 48±44.5, but remained significantly lower than the values observed at baseline. In the ten patients with intact colons, adenomas decreased by sevenfold in the proximal colon (103±73 to 15.1±47.4,P=0.011) and twofold in the distal colon (80±52 to 29.6±37.2,P=0.005). The size of adenomas and the grade of dysplasia also decreased. No correlation could be seen between theAPC mutation site and the response to treatment. CONCLUSION: These data indicate that sulindac reduces the number of adenomas in the entire colon and that the effect seems to be more pronounced in the proximal colon.

Key words

Familial adenomatous polyposis Adenomatous polyposis coli Nonsteroidal anti-inflammatory drugs 

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Copyright information

© The American Society of Colon and Rectal Surgeons 2001

Authors and Affiliations

  • Irene Guldenschuh
    • 1
  • Rainer Hurlimann
    • 1
  • Andreas Muller
    • 1
  • Rudolf Ammann
    • 1
  • Beat Mullhaupt
    • 1
  • Zuzana Dobbie
    • 2
  • Gian-Franco Zala
    • 1
  • Renata Flury
    • 5
  • Walter Seelentag
    • 5
    • 4
  • Jurgen Roth
    • 5
  • Christa Meyenberger
    • 1
  • Michael Fried
    • 1
  • Thomas Hoppeler
    • 3
  • Allan D. Spigelman
    • 6
  • Rodney J. Scott
    • 7
    • 8
  1. 1.From Gastroenterology, Department of Internal MedicineUniversity Hospital ZurichSwitzerland
  2. 2.Department of PathologyUniversity of ZurichSwitzerland
  3. 3.Department of OphthalmologyUniversity of ZurichSwitzerland
  4. 4.Institute of Clinical PathologyZurichSwitzerland
  5. 5.Human Genetics, Department of ResearchUniversity Hospital BaselBaselSwitzerland
  6. 6.Disciplines of Surgical ScienceUniversity of NewcastleAustralia
  7. 7.Hunter Area Pathology ServiceJohn Hunter HospitalNewcastleAustralia
  8. 8.Department of Medical Genetics, Faculty of Medicine and Health SciencesUniversity of NewcastleAustralia

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