Analyses of the individual risk for hepatocellular carcinoma by large scale search of single nucleotide polymorphisms of cytokine genes

据报道，UGT 1A 7的遗传多态性与德国人群中的肝癌相关，UGT 1A 7可以解毒内源性和环境致癌物。在这项研究中，我们评估了该基因与日本HCV感染患者发生HCC风险的相关性。研究了280例日本慢性HCV感染患者（122例HCC）的UGT 1A7基因多态性。我们将UGT 1A7 ^* 1等位基因（赋予较高活性的单倍型）命名为H，将^* 2、^* 3和^* 4等位基因（赋予较低活性的单倍型）命名为L。HCC患者中UGT 1A7 L/L和H/L等位基因的比例（分别为25%和45%）高于非HCC患者（分别为15%和39%），与UGT 1A7 H/H等位基因相比，比值比分别为2.73（95% CI：1.40 - 5.35）和1.80（95% CI：1.05 - 3.09）。UGT1A7多态性与日本HCV感染患者中HCC的存在相关。 ...更多信息 在188例日本慢性HCV感染患者中检测了171个候选基因的NPs，其中包括77例HCC患者。然后在另外188例慢性HCV感染患者（93例HCC）中检测HCC相关SNP。在393个SNPs中，29个基因中的31个SNPs与HCC有显著相关性（P <0.05）。在这31个SNP中，在二次筛选中，三个基因（SCYB14、GFRA1和CRHR2）的三个SNP与HCC显著相关。总之，这些位于SCBY14、CRHR2和GFRA1基因的SNPs将被用作识别日本慢性HCV感染患者中HCC高危人群的标志物。MDM2基因启动子区的单核苷酸多态性（SNP309）最近被证明与人类遗传性和散发性癌症的加速肿瘤形成相关。然而，SNP309与HCC的关联尚不清楚。我们评估了SNP309与日本慢性HCV感染患者发生HCC风险的关系。我们使用荧光聚合酶链反应对435例日本慢性HCV感染患者（包括187例HCC患者和48例健康受试者）的MDM2启动子SNP309进行基因分型。还通过MDM2启动子区的直接测序证实了SNP的存在。SNP309基因G/G基因型在肝癌组中的比例（33%）显著高于非肝癌组（23%），比值比（OR）为2.28（95%可信区间为1.30-3.98）。MDM 2启动子SNP 309与日本慢性丙型肝炎患者中肝癌的存在相关。少

Genetic polymorphisms of UGT1A7, which detoxifies endogenous and environmental carcinogens, have been reported to be associated with HCC in German populations. In this study, we evaluated the association of this gene with the risk of HCC in Japanese HCV-infected patients. Genetic polymorphisms of UGT1A7 were investigated in 280 Japanese patients (122 with HCC) with chronic HCV infections. We designated the UGT1A7^*1 allele (a haplotype confering higher activity) as H and the ^*2, ^*3, and ^*4 alleles (haplotypes confering lower activity) as L. The proportions of UGT1A7 L/L and H/L alleles in patients with HCC (25% and 45%, respectively) were higher than those in patients without HCC (15% and 39%, respectively) with an odds ratio of 2.73 (95% CI:1.40-5.35) and 1.80 (95% CI:1.05-3.09), respectively, compared with the UGT1A7 H/H alleles. The UGT1A7 polymorphisms were associated with the presence of HCC in Japanese HCV-infected patients.To search for SNPs in HCC susceptibility genes, 393 S … More NPs in 171 candidate genes were examined in 188 Japanese patients with chronic HCV infection, including 77 patients with HCC. HCC-related SNPs were then examined in another 188 patients (93 with HCC) with chronic HCV infection. Of the 393 SNPs, 31 SNPs in 29 genes were significantly associated with HCC based on an initial screening (P < 0.05). Of these 31 SNPs, three SNPs of three genes (SCYB14, GFRA1, and CRHR2) were significantly associated with HCC in a secondary screening. In conclusion, These SNPs located in the SCBY14, CRHR2, and GFRA1 genes will be used as markers to identify a subgroup of Japanese patients with chronic HCV infection who are at high risk of developing HCC.A single nucleotide polymorphisms in the promoter region of MDM2 gene, SNP309, has recently been shown to be associated with accelerated tumor formation in both hereditary and sporadic cancers in humans. However, the association of SNP309 with HCC is unknown. We evaluated the association of SNP309 with the risk of HCC development among Japanese patients with chronic HCV infection. We genotyped the SNP309 at the MDM2 promoter in 435 Japanese patients with chronic HCV infection including 187 patients with HCC, as well as 48 healthy subjects, using a fluorogenic polymerase chain reaction. Presence of SNP was also confirmed by direct sequencing of the MDM2 promoter region. The proportion of G/G genotype of the SNP309 in patients with HCC (33%) was significantly higher than that in patients without HCC (23%), with an odds ratio of 2.28 (95% confidence interval, 1.30-3.98). The MDM2 promoter SNP309 is associated with the presence of HCC in Japanese patients with chronic hepatitis C. Less