title: Familial colorectal cancer in Ashkenazim due to a hypermutable tract in APC.
abstract: 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.
authors.affiliation: Johns Hopkins Oncology Center, Baltimore, Maryland 21231, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Laken
authors.forename: G M
authors.initials: GM
authors.lastname: Petersen
authors.forename: S B
authors.initials: SB
authors.lastname: Gruber
authors.forename: C
authors.initials: C
authors.lastname: Oddoux
authors.forename: H
authors.initials: H
authors.lastname: Ostrer
authors.forename: F M
authors.initials: FM
authors.lastname: Giardiello
authors.forename: S R
authors.initials: SR
authors.lastname: Hamilton
authors.forename: H
authors.initials: H
authors.lastname: Hampel
authors.forename: A
authors.initials: A
authors.lastname: Markowitz
authors.forename: D
authors.initials: D
authors.lastname: Klimstra
authors.forename: S
authors.initials: S
authors.lastname: Jhanwar
authors.forename: S
authors.initials: S
authors.lastname: Winawer
authors.forename: K
authors.initials: K
authors.lastname: Offit
authors.forename: M C
authors.initials: MC
authors.lastname: Luce
authors.forename: K W
authors.initials: KW
authors.lastname: Kinzler
authors.forename: B
authors.initials: B
authors.lastname: Vogelstein
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000235:genetics*; D000328:Adult; D001483:Base Sequence; D003062:Codon; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D017931:DNA Primers; D005060:Europe / Q000208:ethnology; D005260:Female; D017491:Genes, APC; D006801:Humans; D007585:Jews / Q000235:genetics*; D008297:Male; D010375:Pedigree; D017354:Point Mutation; D016133:Polymerase Chain Reaction
chemical_list: D003062:Codon; D017931:DNA Primers