Genetic changes of p53, K-ras, and microsatellite instability in gallbladder carcinoma in high-incidence areas of Japan and Hungary.
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.
Nagahashi
Masayuki
M
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.
Ajioka
Yoichi
Y
Lang
Istvan
I
Szentirmay
Zoltan
Z
Kasler
Miklos
M
Nakadaira
Hiroto
H
Yokoyama
Naoyuki
N
Watanabe
Gen
G
Nishikura
Ken
K
Wakai
Toshifumi
T
Shirai
Yoshio
Y
Hatakeyama
Katsuyoshi
K
Yamamoto
Masaharu
M
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*
D016159:Tumor Suppressor Protein p53