Effect of genetic predisposition on the risk of gallbladder cancer in Hungary.
Effect of genetic predisposition on the risk of gallbladder cancer in Hungary.
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2008-07
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通讯作者：
A. Kimura;Y. Tsuchiya;I. Láng;Szentirmay Zoltán;H. Nakadaira;Y. Ajioka;C. Kiyohara;Mari Oyama;Kazutoshi Nakamura
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作者：
A. Kimura;Y. Tsuchiya;I. Láng;Szentirmay Zoltán;H. Nakadaira;Y. Ajioka;C. Kiyohara;Mari Oyama;Kazutoshi Nakamura
CYP 1A 1多态性与日本女性胆囊癌（GBC）风险增加相关。然而，GBC在匈牙利的遗传风险因素，那里的人口有一个相对较高的GBC的发病率，还没有得到很好的研究。因此，我们在匈牙利测试了CYP 1A 1 T3801 C、CYP 1A 1 Ile 462 Val、GSTM 1缺失和TP 53 Arg 72 Pro与GBC之间的关联。从100名对照（52名男性和48名女性）的外周血和43例石蜡包埋的组织（6名男性和37名女性）中提取基因组DNA。由于男性数量较少，病例对照分析仅限于女性。在37例女性病例中，21例（56.8%）被诊断为腺癌，其余16例（43.2%）被分类为非腺癌。Ile/瓦尔基因型和瓦尔等位基因的优势比（OR）分别为8.9（95%CI：2.9-27.4）和4.4（95%CI：1.7-11.1）。CYP 1A 1 Ile 462 Val和GSTM 1的联合变异基因型（37.8%vs.8.3%）或CYP 1A 1 Ile 462 Val和TP 53 Arg 72 Pro的联合变异基因型（24.3%vs.0%）在病例组中的发生率显著高于对照组。Ile/瓦尔基因型与腺癌（OR 9.2; 95% CI：2.6-32.6）和非腺癌（OR 8.4; 95% CI：2.2-32.4）风险增加显著相关。此外，Arg/Pro基因型增加了非腺癌的风险（OR 3.8; 95% CI：1.2-12.8）。瓦尔等位基因可能不仅在日本，而且在匈牙利妇女GBC的发展。我们的研究结果为进一步研究匈牙利GBC风险的遗传变异提供了依据。
A CYP1A1 polymorphism has been associated with an increased risk for gallbladder cancer (GBC) in Japanese women. However, genetic risk factors for GBC in Hungary, where the population has a relatively high GBC incidence, has not been well studied. We therefore tested associations between CYP1A1 T3801C, CYP1A1 Ile462Val, GSTM1deletion, and TP53 Arg72Pro and GBC in Hungary. Genomic DNA was extracted from peripheral blood of 100 controls (52 men and 48 women) and from the tissue embedded in paraffin of 43 cases (6 men and 37 women). The case-control analysis was limited to females due to a small number of males. Of 37 female cases, 21 (56.8%) were diagnosed as adenocarcinoma, and the remaining 16 (43.2%) were classified as non-adenocarcinoma. The odds ratios (ORs) for the Ile/Val genotype and the Val allele were 8.9 (95% CI: 2.9-27.4) and 4.4 (95% CI: 1.7-11.1), respectively. The occurrence of the combined variant genotypes of CYP1A1 Ile462Val and GSTM1 (37.8% vs. 8.3%) or CYP1A1 Ile462Val and TP53 Arg72Pro (24.3% vs. 0%) was significantly higher in the cases than in the controls. The Ile/Val genotype was significantly associated with an increased risk of adenocarcinoma (OR 9.2; 95% CI: 2.6-32.6) and non-adenocarcinoma (OR 8.4; 95% CI: 2.2-32.4). Additionally, the Arg/Pro genotype increased risk of non-adenocarcinoma (OR 3.8; 95% CI: 1.2-12.8). The Val allele may contribute to the development of GBC not only in Japanese but also in Hungarian women. Our results provide a rationale for further studies of genetic variation on the risk of GBC in Hungary.