Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC

Steven J. Laken, Gloria M. Petersen, Stephen B. Gruber, Carole Oddoux, Harry Ostrer, Francis M. Giardiello, Stanley R. Hamilton, Heather Hampel, Arnold Markowitz, David Klimstra, Suresh Jhanwar, Sidney Winawer, Kenneth Offit, Michael C. Luce, Kenneth W. Kinzler, Bert Vogelstein

Research output: Contribution to journalArticlepeer-review

503 Scopus citations


Approximately 130,000 cases of colorectal cancer (CRC) are diagnosed in the United States each year, and about 15% of these have a hereditary component. Two well-defined syndromes, familial adenomatous polyposis (FAP) and hereditary non-polyposis colorectal cancer (HNPCC), account for up to 5% of the total new cases of CRC. Truncating APC mutations are responsible for FAP, and defective mismatch repair genes cause HNPCC. However, the genes responsible for most of the familial cases are unknown. Here we report a mutation (T to A at APC nucleotide 3920) found in 6% of Ashkenazi Jews and about 28% of Ashkenazim with a family history of CRC. Rather than altering the function of the encoded protein, this mutation creates a small hypermutable region of the gene, indirectly causing cancer predisposition.

Original languageEnglish (US)
Pages (from-to)79-83
Number of pages5
JournalNature Genetics
Issue number1
StatePublished - 1997

ASJC Scopus subject areas

  • Genetics


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