Wang Xiao Qi, Luk John M, Garcia-Barcelo Mercè, Miao Xiaoping, Leung Pauline P, Ho David W, Cheung Siu Tim, Lam Brian Y, Cheung Cindy K, Wong Ashley S, Lau Silvana S, So Man Ting, Yu Wan Ching, Cai Qi, Liu Karen S, Hui Chee Kin, Lau George K, Poon Ronnie T P, Wong John, Fan Sheung Tat
Department of Surgery, The University of Hong Kong, Pokfulam, Hong Kong.
Clin Cancer Res. 2006 Sep 1;12(17):5248-52. doi: 10.1158/1078-0432.CCR-06-0558.
Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients. Consequently, it is highly relevant to assess whether the presence of these single nucleotide polymorphisms in the general population represents a risk to the development of HCC.
We conducted a case-control study including 164 HCC and 99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze genotypes and haplotypes.
Genotypes 651TT [OR, 2.62; 95% confidence interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles were also overrepresented in HCC patients and, in particular, the T-G haplotype was the most prevalent in HCC patients when compared with healthy controls (OR, 1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant splicing observed in tumor tissues. There was no significant difference in genotype and allele frequencies between cirrhosis patients and controls.
The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population.
肝细胞癌（HCC）是最常见的肝癌形式，是全球癌症死亡的主要原因。我们之前表明，肝组织中肝肠钙黏蛋白基因CDH17的异常mRNA剪接是由两个CDH17单核苷酸多态性（651T和IVS6 + 35G）的特定组合引发的。CDH17异常剪接与HCC患者的肿瘤播散和较短生存期高度相关。因此，评估普通人群中这些单核苷酸多态性的存在是否对HCC的发生构成风险具有高度相关性。
我们进行了一项病例对照研究，包括164例HCC患者、99例肝硬化患者和293名健康对照。通过聚合酶链反应（PCR）和直接测序进行基因分型。使用优势比（OR）和卡方分析来分析基因型和单倍型。
基因型651TT [OR，2.62；95%置信区间（95%CI），1.34 - 5.03]和IVS6 + 35 GG（OR，1.95；95%CI，1.04 - 3.62）与HCC疾病高度相关。651T（C>T）和IVS6 + 35G（A>G）等位基因在HCC患者中也过度表达，特别是与健康对照相比，T - G单倍型在HCC患者中最为普遍（OR，1.57；95%CI，1.167 - 2.109；P = 0.004），这与在肿瘤组织中观察到的异常剪接一致。肝硬化患者和对照之间的基因型和等位基因频率没有显著差异。
CDH17的功能性T - G单倍型（651 C>T和IVS6 + 35A>G）是中国人群中HCC发生的遗传易感性因素。
