Correspondence

Sulindac in Familial Adenomatous Polyposis

N Engl J Med 2002; 347:615August 22, 2002

Article

To the Editor:

Giardiello et al. (April 4 issue)1 conclude that sulindac does not delay the occurrence or reduce the number or size of colorectal adenomas in patients bearing a mutation of the adenomatous polyposis coli (APC) gene. The authors do not take into account two important factors: the position of the mutation in the germ-line APC gene and the level of expression of the wild-type allele in normal colonic mucosa and in adenomas. In familial adenomatous polyposis, there is a strong correlation between the location of the mutation in the APC gene and the age at onset and number and size of adenomas.2,3 Moreover, polymorphism of the mutated allele also influences the phenotype.4 This information is missing from the report by Giardiello et al.

Rafaël Levy, M.D.
Clinique de l'Orangerie, 94170 Le Perreux-sur-Marne, France
rdlevy@club-internet.fr

4 References

1. 1

   Giardiello FM, Yang VW, Hylind LM, et al. Primary chemoprevention of familial adenomatous polyposis with sulindac. N Engl J Med 2002;346:1054-1059
   Full Text | Web of Science | Medline

2. 2

   Nagase H, Miyoshi Y, Horii A, et al. Correlation between the location of germ-line mutations in the APC gene and the number of colorectal polyps in familial adenomatous polyposis patients. Cancer Res 1992;52:4055-4057
   Web of Science | Medline

3. 3

   Gardner RJ, Kool D, Edkins E, et al. The clinical correlates of a 3' truncating mutation (codons 1982-1983) in the adenomatous polyposis coli gene. Gastroenterology 1997;113:326-331
   CrossRef | Web of Science | Medline

4. 4

   Spirio LN, Samowitz W, Robertson J, et al. Alleles of APC modulate the frequency and classes of mutations that lead to colon polyps. Nat Genet 1998;20:385-388
   CrossRef | Web of Science | Medline

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