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
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.