title: Genetic analysis of familial colorectal cancer in Israeli Arabs.
abstract: Colorectal cancers (CRC) among Israeli Arabs differ from those diagnosed in Jewish Israeli individuals in two manners: an earlier age of occurrence and a low frequency. These differences are unaccounted for and thus prompted us to perform genetic analysis in Israeli Arab CRC patients. Analysis included the major Hereditary non-polyposis colorectal cancer (HNPCC) genes and the APC I1307K mutation (MIM# 175100.0029). Twenty-five patients and 25 relatives from 24 unrelated families were clinically classified according to personal and familial cancer history. If MSI (microsatellite instability) was displayed in tumor tissue, patients underwent mutation analysis of the MSH2 and MLH1 genes using DGGE (denaturing gradient gel electrophoresis) and sequencing. MSI was detected in 9/21 of the tumors tested (43%). Two novel missense mutations were diagnosed among 11 fully analyzed patients: a change of A to G at position 380 in MSH2 (N127S), and a D601G mutation in MLH1. The I1307K mutation was detected in 8 families (8/24, 33.3%). This is the first report of genetic analysis in familial CRC associated genes among Israeli Arabs. We suggest that the I1307K mutation may contribute to CRC in Israeli Arabs and that inactivating mutations of MSH2 and MLH1 may not be a major cause for early onset CRC.
authors.affiliation: Department of Gastroenterology, The Chaim Sheba Medical Center, Tel-Hashomer, Israel. Rakefet.Shtoyerman@Weizmann.Ac.Il
authors.forename: Rakefet
authors.initials: R
authors.lastname: Chen-Shtoyerman
authors.forename: Livia
authors.initials: L
authors.lastname: Theodor
authors.forename: Ester
authors.initials: E
authors.lastname: Harmati
authors.forename: Eitan
authors.initials: E
authors.lastname: Friedman
authors.forename: Samir
authors.initials: S
authors.lastname: Dacka
authors.forename: Yael
authors.initials: Y
authors.lastname: Kopelman
authors.forename: Amos
authors.initials: A
authors.lastname: Sternberg
authors.forename: Raz
authors.initials: R
authors.lastname: Zarivach
authors.forename: Simon
authors.initials: S
authors.lastname: Bar-Meir
authors.forename: Zvi
authors.initials: Z
authors.lastname: Fireman
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein / Q000235:genetics; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D018912:Arabs / Q000235:genetics*; D002352:Carrier Proteins; D015179:Colorectal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000453:epidemiology / Q000235:genetics; D004268:DNA-Binding Proteins; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006801:Humans; D007557:Israel / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein; D020125:Mutation, Missense / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D025601:Adenomatous Polyposis Coli Protein; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C501486:MLH1 protein, human; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein