title: Genetic analyses in consecutive israeli jewish colorectal cancer patients.
abstract: OBJECTIVE
  Two APC germline mutations, E1317Q and I1307K, have been linked to colorectal cancer (CRC) risk. Whereas the I1307K variant is almost exclusively encountered in (Ashkenazi) Jews, E1317Q is not restricted to certain ethnic populations. Data on its contribution to CRC risk in Jewish patients are sparse.
  
  
  OBJECTIVE
  To assess the contribution of E1317Q to CRC development in the Jewish population.
  
  
  METHODS
  A total of 538 consecutive Israeli Jewish CRC patients and 440 controls were genotyped for E1317Q. In addition, the rate of the I1307K APC missense mutation and the two predominant Jewish mutations in hMSH2, A636P, and 324delCA, associated with hereditary nonpolyposis colon cancer (HNPCC), were determined.
  
  
  RESULTS
  The E13117Q missense mutation was detected in 6/538 (1%) of CRC patients and 5/440 (1%) of controls. The I1307K variant was found in 8% of all patients and in 11% (35/322) of patients of Ashkenazi Jewish descent. Carriers and noncarrier CRC patients did not differ in age of onset or associated colonic adenomatous polyps. The carrier rate among controls was 5% among Ashkenazim and 1.6% among non-Ashkenazi individuals. The 324delCA hMSH2 mutation was not observed in this cohort, and 4 of 322 Ashkenazi patients (1.2%) displayed the A636P mutation.
  
  
  CONCLUSIONS
  In Jewish CRC patients the E1317Q variant plays little if any role in colorectal cancer susceptibility and genetic testing for this variant is not warranted. The I1307K mutation is associated with a moderate excess risk for CRC, but age of onset seems not to be earlier and this variant is not associated with a multiple colonic polyp phenotype. Founder mutations in hMSH2 are rare in consecutive CRC patients.
authors.affiliation: Institute of Gastroenterology and the Susanne Levy Gertner Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Herma H
authors.initials: HH
authors.lastname: Fidder
authors.forename: Arie
authors.initials: A
authors.lastname: Figer
authors.forename: Ravit
authors.initials: R
authors.lastname: Geva
authors.forename: Dov
authors.initials: D
authors.lastname: Flex
authors.forename: Hagit
authors.initials: H
authors.lastname: Schayek
authors.forename: Benjamin
authors.initials: B
authors.lastname: Avidan
authors.forename: Simon Bar
authors.initials: SB
authors.lastname: Meir
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000208:ethnology* / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D017491:Genes, APC / Q000502:physiology*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000208:ethnology; D007585:Jews; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000235:genetics*; D009367:Neoplasm Staging; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D004273:DNA, Neoplasm