The relationship between frequencies of extracolonic manifestations and the position of APC germline mutation in patients with familial adenomatous polyposis

Jpn J Clin Oncol. 2000 Feb;30(2):82-8. doi: 10.1093/jjco/hyd017.


Background: Familial adenomatous polyposis (FAP) patients develop various extracolonic lesions; however, the relationship between germline mutation of the APC gene and extracolonic manifestations is mostly unknown. To examine the genotype-phenotype relationship, we compared the APC mutation and clinical data.

Methods: Germline mutations from codon 157 to 1465 of the APC gene were identified in 39 families of FAP and clinical data were collected from 80 patients of these families. Germline mutations were classified into two groups: mutations from exon 4 to 9 (codon 157 to 416, Group 1) and those from exon 10 to 15H (codon 564 to 1465, Group 2). The complication rates of extracolonic manifestations were compared between these two groups.

Results: Frequencies of duodenal polyps and gastric adenomas in Group 2 were higher than those in Group 1 (p < 0.0001 and p < 0.0004, respectively) and development of osteoma was more frequent in Group 2 (p = 0.01). The number of colorectal polyps and retinal pigments also correlated with the germline mutation, which was consistent with previous reports. However, such correlations were less obvious with regard to gastric fundic polyps, desmoid tumors, soft tissue tumors and colorectal cancer.

Conclusion: There are two types with regard to extracolonic manifestations of FAP: one is more severely affected according to the position of germline mutation of the APC gene and the other is not affected.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / etiology
  • Adenoma / genetics*
  • Adenomatous Polyposis Coli / complications
  • Adenomatous Polyposis Coli / genetics*
  • Adenomatous Polyposis Coli / pathology
  • Adolescent
  • Adult
  • Cytoskeletal Proteins / genetics*
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics*
  • Duodenal Diseases / etiology
  • Duodenal Diseases / genetics*
  • Female
  • Genes, APC*
  • Genotype
  • Germ-Line Mutation*
  • Humans
  • Male
  • Middle Aged
  • Pedigree
  • Phenotype
  • Polyps
  • Stomach Neoplasms / etiology
  • Stomach Neoplasms / genetics*


  • Cytoskeletal Proteins
  • DNA, Neoplasm