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Sapna Syngal, MD, MPH; Deborah Schrag, MD, MPH; Myron Falchuk, MD; Nadine Tung, MD; Francis A. Farraye, MD; Daniel Chung, MD; Mary Wright; Amy Whetsell; Glenn Miller, PhD; Judy E. Garber, MD, MPH

JAMA. 2000;284:857-860.

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.

Author Affiliations: Division of Gastroenterology, Brigham and Women's Hospital (Drs Syngal and Farraye), Population Sciences, Dana-Farber Cancer Institute (Drs Syngal, Garber, and Schrag), Divisions of Gastroenterology (Dr Falchuk) and Oncology (Dr Tung), Beth Israel-Deaconess Medical Center, Gastrointestinal Unit, Massachusetts General Hospital (Dr Chung), Harvard Medical School, and Genzyme Corporation (Mss Wright and Whetsell and Dr Miller), Boston, Mass. Dr Schrag is now with Memorial Sloan-Kettering Cancer Center, New York, NY.

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