Phenotypic characteristics associated with the APC gene I1307K mutation in Ashkenazi Jewish patients with colorectal polyps

JAMA. 2000 Aug 16;284(7):857-60. doi: 10.1001/jama.284.7.857.


Context: The I1307K mutation of the APC gene is found in approximately 6% of the Ashkenazi Jewish population and is associated with elevated risk of colorectal cancer. The incidence of the mutation in patients with colorectal adenomas is unknown.

Objectives: To determine the carrier rate of the I1307K mutation in Ashkenazi Jewish patients with a history of colorectal polyps but without colorectal cancer and to compare phenotypic characteristics and family history of carriers vs noncarriers.

Design, setting, and patients: A total of 231 patients who had at least 1 large bowel polyp diagnosed between January 1, 1992, and January 31, 1999, at 1 of 5 centers in Boston, Mass, were included, of whom 183 were Ashkenazi Jewish. DNA was isolated from cheek swab samples.

Main outcome measures: Presence of the I1307K variant in the APC gene.

Results: The I1307K variant was identified in 22 (14%) of 161 Ashkenazi Jewish patients with a history of adenomatous polyps and in 1 (5%) of 20 Ashkenazi Jewish patients with hyperplastic polyps. The phenotypic features of adenomas, family history of polyps, colorectal cancer, and other cancers were indistinguishable between I1307K carriers and noncarriers.

Conclusions: The frequency of the APC I1307K mutation is elevated in Ashkenazi Jewish patients with adenomatous polyps, but not hyperplastic polyps. The I1307K mutation represents a novel paradigm for cancer-predisposing genes, as it is associated with moderately increased risk of neoplasia without other associated distinguishing phenotypic features. JAMA. 2000;284:857-860

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Colonic Polyps / ethnology*
  • Colonic Polyps / genetics*
  • Colorectal Neoplasms / epidemiology
  • Colorectal Neoplasms / genetics
  • DNA Mutational Analysis
  • Female
  • Genes, APC*
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Jews / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Phenotype