MDM2 promoter SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis C
MDM2 promoter SNP309 is associated with the risk of hepatocellular carcinoma in patients with chronic hepatitis C
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DOI：
10.1158/1078-0432.ccr-06-0111
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发表时间：
2006-08-15
影响因子：
11.5
通讯作者：
Omata, Masao
中科院分区：
文献类型：
--
作者：
Dharel, Narayan;Kato, Naoya;Omata, Masao
目的：MDM 2基因启动子区的单核苷酸多态性（SNP）SNP 309最近被证明与人类遗传性和散发性癌症的加速肿瘤形成有关。然而，SNP 309与肝细胞癌的关联尚不清楚。我们评估了SNP 309与日本慢性丙型肝炎病毒感染患者肝细胞癌发展风险的相关性。实验设计：我们对435例日本慢性丙型肝炎病毒感染患者（包括187例肝细胞癌患者和48例健康受试者）的MDM 2启动子的SNP 309进行了基因分型，采用荧光PCR。结果：肝癌组SNP 309基因G/G基因型比例（33%）显著高于非肝癌组（23%），比值比（95%可信区间）为2.28（1.30-3.98）。多变量分析显示，MDM 2 SNP 309（G/G vs T/T）、年龄>60岁、男性、肝硬化、血清甲胎蛋白>20 μ g/L和血清白蛋白
Purpose: A single nucleotide polymorphism (SNP) 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 hepatocellular carcinoma is unknown. We evaluated the association of SNP309 with the risk of hepatocellular carcinoma development among Japanese patients with chronic hepatitis C virus infection.Experimental Design: We genotyped the SNP309 at the MDM2 promoter in 435 Japanese patients with chronic hepatitis C virus infection, including 187 patients with hepatocellular carcinoma and 48 healthy subjects, using a fluorogenic PCR. Presence of SNP was also confirmed by direct sequencing of the MDM2 promoter region.Results: The proportion of G/G genotype of the SNP309 in patients with hepatocellular carcinoma (33%) was significantly higher than that in patients without hepatocellular carcinoma (23%), with an odds ratio (95% confidence interval) of 2.28 (1.30-3.98). A multivariate analysis revealed that MDM2 SNP309 (G/G versus T/T), age >60 years, male gender, presence of cirrhosis, serum a-fetoprotein >20 mu g/L, and serum albumin