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

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