丙型肝炎相关肝细胞癌的基因组风险。
Genomic risk of hepatitis C-related hepatocellular carcinoma.
机构信息
Cancer Program, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA, USA.
出版信息
J Hepatol. 2012 Mar;56(3):729-30. doi: 10.1016/j.jhep.2011.08.015. Epub 2011 Sep 29.
To identify the genetic susceptibility factor(s) for hepatitis C virus-induced hepatocellular carcinoma (HCV-induced HCC), we conducted a genome-wide association study using 432,703 autosomal SNPs in 721 individuals with HCV-induced HCC (cases) and 2890 HCV-negative controls of Japanese origin. Eight SNPs that showed possible association (P <1 10(⁻5)) in the genome-wide association study were further genotyped in 673 cases and 2596 controls. We found a previously unidentified locus in the 50 flanking region of MICA on 6p21.33 (rs2596542, P(combined) = 4.21 10(⁻13), odds ratio = 1.39) to be strongly associated with HCV induced HCC. Subsequent analyses using individuals with chronic hepatitis C (CHC) indicated that this SNP is not associated with CHC susceptibility (P = 0.61) but is significantly associated with progression from CHC to HCC (P = 3.13 10(⁻8)). We also found that the risk allele of rs2596542 was associated with lower soluble MICA protein levels in individuals with HCV-induced HCC (P = 1.38 10(⁻13)).
为了确定丙型肝炎病毒（HCV）诱导的肝细胞癌（HCV- HCC）的遗传易感性因素，我们使用 721 名 HCV- HCC 患者（病例）和 2890 名日本 HCV 阴性对照的 432703 个常染色体 SNP 进行了全基因组关联研究。在全基因组关联研究中，8 个 SNP 显示出可能的关联（P <1 10(-5))，进一步在 673 例病例和 2596 例对照中进行了基因分型。我们在 6p21.33 上发现了一个以前未识别的位于 MICA 5'侧翼区域的新位点（rs2596542，P(联合)=4.21 10(-13)，优势比=1.39）与 HCV 诱导的 HCC 强烈相关。使用慢性丙型肝炎（CHC）患者进行的后续分析表明，该 SNP 与 CHC 易感性无关（P=0.61），但与从 CHC 进展为 HCC 显著相关（P=3.13 10(-8))。我们还发现，rs2596542 的风险等位基因与 HCV- HCC 患者可溶性 MICA 蛋白水平较低有关（P=1.38 10(-13))。
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