title: The I1307K polymorphism of the APC gene in colorectal cancer.
abstract: OBJECTIVE
  Colorectal cancer is one of the most frequent cancers in humans. Recently, a germline missense mutation, I1307K, was identified in the adenomatous polyposis coli (APC) gene that was suggested to increase cancer predisposition in Ashkenazi Jews. However, a second study indicated that the I1307K mutation did not contribute greatly to the risk of colon cancer in Ashkenazi breast-ovarian cancer families, and a role of mismatch repair deficiency was suggested. This study investigated the frequency of the I1307K mutation in several non-Ashkenazi Jewish populations. We also compared the distribution and frequency of APC mutations from colon tumors that were positive and negative for the I1307K mutation. Finally, the association between the presence of mutations in the I1307K region and mismatch repair deficiency was studied.
  
  
  METHODS
  We tested for I1307K in 345 patients who were not Ashkenazi Jews using a heteroduplex screen. We also performed an extensive mutational analysis in this region of the APC gene on DNA extracted from 240 Italian, Finnish, and Hawaiian-Japanese colon tumors and determined replication error status.
  
  
  RESULTS
  The I1307K mutation was not found among 345 non-Ashkenazis. Somatic mutations occurred at a lower frequency and were more randomly distributed when the I1307K allele was not present. The most common characteristic somatic mutation occurring around codon 1307 in I1307K-positive patients did not occur in tumors negative for the I1307K mutation. An association between mutations in the region around APC codon 1307 and mismatch repair deficiency was not found.
  
  
  CONCLUSIONS
  Our findings support the hypothesis that the I1307K mutation is unique to the Ashkenazi Jews, contributes to tumor predisposition in colorectal cancer, and is unrelated to mismatch repair deficiency.
authors.affiliation: Department of Pathology, Ohio State University, Columbus, Ohio 43210, USA.
authors.forename: T W
authors.initials: TW
authors.lastname: Prior
authors.forename: R B
authors.initials: RB
authors.lastname: Chadwick
authors.forename: A C
authors.initials: AC
authors.lastname: Papp
authors.forename: A N
authors.initials: AN
authors.lastname: Arcot
authors.forename: A M
authors.initials: AM
authors.lastname: Isa
authors.forename: D K
authors.initials: DK
authors.lastname: Pearl
authors.forename: G
authors.initials: G
authors.lastname: Stemmermann
authors.forename: A
authors.initials: A
authors.lastname: Percesepe
authors.forename: A
authors.initials: A
authors.lastname: Loukola
authors.forename: L A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: A
authors.initials: A
authors.lastname: De La Chapelle
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000595:Amino Acid Sequence; D001483:Base Sequence; D003062:Codon / Q000235:genetics; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics*; D004247:DNA / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D017491:Genes, APC; D005820:Genetic Testing; D006801:Humans; D007585:Jews; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003062:Codon; D003598:Cytoskeletal Proteins; D004247:DNA