title: Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.
abstract: OBJECTIVE
  To disclose geographic differences in genetic changes involved in gallbladder carcinogenesis between two distinct high-incidence areas of Japan and Hungary.
  
  
  METHODS
  We examined 42 cases of gallbladder carcinoma: 22 Japanese and 20 Hungarian cases. p53 mutations at exons 5 to 8 and K-ras mutations at codon 12 were tested by direct sequencing. Microsatellite instability was determined from fluorescent dye-labeled PCR amplifications of five-microsatellite markers (BAT-25, BAT-26, D2S123, D5S346, and D17S250).
  
  
  RESULTS
  Mutations of p53 were detected in 11 of 22 Japanese cases and 6 of 18 Hungarian cases (11/22 vs 6/18, P = 0.348). Transition at CpG sites was found in none of 11 Japanese cases and 2 of 6 Hungarian cases; the difference was marginally significant (0/11 vs 2/6, P = 0.110). K-ras mutations were detected in only one of the Hungarian cases. Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047).
  
  
  CONCLUSIONS
  It appears that the p53 mutations and MSI differ in patients with gallbladder carcinoma between two distinct high-incidence areas. Geographic variation might exist in the process of gallbladder carcinogenesis.
authors.affiliation: Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-dori, Chuo-ku, Niigata 951-8510, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nagahashi
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ajioka
authors.forename: Istvan
authors.initials: I
authors.lastname: Lang
authors.forename: Zoltan
authors.initials: Z
authors.lastname: Szentirmay
authors.forename: Miklos
authors.initials: M
authors.lastname: Kasler
authors.forename: Hiroto
authors.initials: H
authors.lastname: Nakadaira
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Yokoyama
authors.forename: Gen
authors.initials: G
authors.lastname: Watanabe
authors.forename: Ken
authors.initials: K
authors.lastname: Nishikura
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Wakai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Shirai
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Hatakeyama
authors.forename: Masaharu
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005706:Gallbladder Neoplasms / Q000208:ethnology* / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D006801:Humans; D006814:Hungary / Q000453:epidemiology; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D016159:Tumor Suppressor Protein p53