Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk.
Functional genetic variant of WW domain-containing oxidoreductase (WWOX) gene is associated with hepatocellular carcinoma risk.
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DOI：
10.1371/journal.pone.0176141
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Chou YE
中科院分区：
文献类型：
--
作者：
Lee HL;Cheng HL;Liu YF;Chou MC;Yang SF;Chou YE
肝细胞癌（HCC）是世界上最常见的恶性肿瘤之一。人含WW结构域的氧化还原酶（WWOX）基因已被鉴定为多种癌症的肿瘤抑制基因。我们假设WWOX的遗传变异与HCC风险相关。从708名正常对照和354例HCC患者中检测了WWOX基因的5个单核苷酸多态性（SNPs）。我们发现WWOX单核苷酸多态性（SNP）rs73569323与HCC风险降低之间存在显著相关性。在调整潜在混杂因素后，WWOX rs11545028上至少有一个T等位基因的患者可能具有显著较小的肿瘤大小、降低的甲胎蛋白和丙氨酸氨基转移酶（ALT）水平。此外，WWOX中SNP rs12918952处的A等位基因赋予更高的血管侵袭风险。另外的计算机模拟分析也表明，WWOX rs12918952多态性倾向于影响WWOX表达，这反过来又有助于肿瘤血管侵袭。总之，WWOX的遗传变异可能是早期HCC发生的重要预测因子和疾病进展的可靠生物标志物。
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Human WW domain-containing oxidoreductase (WWOX) gene has been identified as a tumor suppressor gene in multiple cancers. We hypothesize that genetic variations in WWOX are associated with HCC risk. Five single-nucleotide polymorphisms (SNPs) of the WWOX gene were evaluated from 708 normal controls and 354 patients with HCC. We identified a significant association between a WWOX single nucleotide polymorphism (SNP), rs73569323, and decreased risk of HCC. After adjustment for potential confounders, patients with at least one T allele at rs11545028 of WWOX may have a significantly smaller tumor size, reduced levels of α-fetoprotein and alanine aminotransferase (ALT). Moreover, the A allele at SNP rs12918952 in WWOX conferred higher risk of vascular invasion. Additional in silico analysis also suggests that WWOX rs12918952 polymorphism tends to affect WWOX expression, which in turn contributes to tumor vascular invasion. In conclusion, genetic variations in WWOX may be a significant predictor of early HCC occurrence and a reliable biomarker for disease progression.