International and Epidemiological Studies on the Causes of Gallbladder Cancer in Hungary

我们在日本和智利开展了胆囊癌（GBC）流行病学研究，这两个国家的胆囊癌死亡率分别为世界第5位和第1位。下一步，我们研究了匈牙利GBC的特点，因为它的排名在世界上被报道为2^<和>。(1) BBC病例-对照研究：我们从匈牙利布达佩斯的医院收集了42例GBC合并GS的病例，并在无GBC但有GS的医院门诊患者中收集了30例对照。应用条件logistic分析发现，辣椒食用量和年龄与GBC的发生显著相关。(2)细胞色素P450 1A1基因多态性：为了阐明GBC易感性的个体差异，我们研究了42例GBC患者和100例对照组中CYP1A1基因Msp1和Ile-Val多态性的频率。Msp1和Ile-Val多态性的突变基因型及其等位基因频率在两者之间无统计学差异。(3) p53、K-ras密码子12突变和微卫星不稳定性（Microsatellite Instability， MSI）：我们收集了匈牙利20例GBC和日本22例GBC。在匈牙利，18例患者中有6例（33.3%）出现p53突变，在日本，22例患者中有11例（50.0%）出现p53突变，但没有发现差异。匈牙利的碱基变化谱为过渡型，而日本的碱基变化谱均为翻转型。两国之间K-ras突变没有差异。GBC的MSI-H发生率在匈牙利为1/15(6.7%)，在日本为8/19（42.1%）。他们之间有显著的差异。综上所述，智利的情况表明，食用辣椒也是一种风险因素。此外，匈牙利的p53突变谱与智利相似，但与日本不同。

We have conducted epidemiological studies on gallbladder cancer (GBC) in Japan and Chile, where the ranks of mortality rate for GBC were the 5^<th> and the 1^<st>, respectively, in the world. As a next step, we studied the characteristics of GBC in Hungary since its rank was reported as the 2^<nd> in the world.(1)Case-Control Study of BBC : We collected 42 cases of GBC with GS from hospitals in Budapest, Hungary and 30 controls among outpatients of the hospital without GBC, but with GS. When a conditional logistic analysis was applied, the consumption of chili pepper and the age were found to be significantly related to the occurrence of GBC.(2)Genetic Polymorphisms of Cytochrome P450 1A1 : In order to clarify the individual differences in susceptibility to GBC, we investigated the frequency of the Msp1 and Ile-Val polymorphisms of the CYP1A1 gene, in 42 cases of GBC and 100 controls. There were no statistical differences in the frequencies of the mutant genotypes of Msp1 and Ile-Val polymorphism or their alleles between them.(3)Mutations of p53, K-ras codon 12 and Microsatellite Instability (MSI) : We collected 20 GBC in Hungary and 22 cases in Japan. Mutations of p53 were found in 6 out of 18 cases (33.3%) in Hungary and in 11 out of 22 cases (50.0%) in Japan, but no difference was found. Base-change spectra of mutation in Hungary were characterized as transition type, while in Japan they were all transversion type. There was no difference in K-ras mutations between two countries. The frequencies of MSI-H of GBC were 1/15 (6.7%) in Hungary and 8/19 (42.1%) in Japan. There was a significant difference between them.In conclusion, the consumption of chili pepper was also disclosed as a risk factor, as shown in Chile. In addition, the mutation spectra of p53 in Hungary were similar to those in Chile, but different from those in Japan.