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

Authors: Laken, S. J.; Petersen, G. M.; Gruber, S. B.; Oddoux, C.; Ostrer, H.; Giardiello, F. M.; Hamilton, S. R.; Hampel, H.; Markowitz, A.; Klimstra, D.; Jhanwar, S.; Winawer, S.; Offit, K.; Luce, M. C.; Kinzler, K. W.; Vogelstein, B.
Article 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.
Keywords: adult; controlled study; major clinical study; polymerase chain reaction; colorectal cancer; cancer susceptibility; pedigree; europe; genetic susceptibility; base sequence; familial cancer; dna primers; codon; point mutation; jews; colorectal neoplasms, hereditary nonpolyposis; jew; nucleic acid base substitution; adenomatous polyposis coli; familial colon polyposis; colon polyposis; genes, apc; humans; human; male; female; priority journal; article
Journal Title: Nature Genetics
Volume: 17
Issue: 1
ISSN: 1061-4036
Publisher: Nature Publishing Group  
Date Published: 1997-09-01
Start Page: 79
End Page: 83
Language: English
DOI: 10.1038/ng0997-79
PUBMED: 9288102
PROVIDER: scopus
Notes: Article -- Export Date: 17 March 2017 -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    519 Offit
  2. Arnold J Markowitz
    109 Markowitz
  3. David S Klimstra
    852 Klimstra
  4. Suresh C Jhanwar
    217 Jhanwar
  5. Sidney J Winawer
    145 Winawer