School of Nursing, Chung Shan Medical University, 110, Section 1, Chien-Kuo N. Road, Taichung, Taiwan, ROC.
Med Oncol. 2012 Dec;29(4):2771-9. doi: 10.1007/s12032-012-0189-9. Epub 2012 Feb 29.
The aim of this study was to estimate the relationship between gene polymorphisms of CCL5-28, CCL5-403, and CCR5 to the susceptibility of hepatocellular carcinoma (HCC). A total of 449 subjects, including 347 healthy controls and 102 patients with HCC, were recruited in this study and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to investigate the impact of these two polymorphic variants on HCC. A significant association between HCC susceptibility and genetic polymorphism, CG heterozygotes of CCL5-28 (AOR=2.35; 95% CI=1.27-4.33, p=0.006), AA homozygotes of CCL5-403 (AOR=5.18; 95% CI=2.25-11.91, p=0.0001), and AA homozygotes of CCR5 (AOR=2.47; 95% CI=1.24-4.90, p=0.009), was found compared with wild genotype after adjusting for other confounders. It was detected that synergistic effect between gene-to-gene polymorphisms increased the risk to have HCC among individuals with CG or GG of CCL5-28, and GA or AA of CCL-403, and GA or AA of CCR5 (AOR=3.42; 95% CI=1.39-8.38, p=0.007) compared to individuals with wild genotypes of CCL5-28, CCL-403, and CCR5. Also, alcohol or tobacco consumption increased the risk to have HCC among subjects with CG heterozygotes of CCL5-28 (alcohol: p=0.001; tobacco: p=0.006), AA homozygotes (alcohol: p=0.0004; tobacco: p≤0.0001) or GA heterozygotes (tobacco: p=0.03) of CCL5-403, and AA homozygotes of CCR5 (alcohol: p=0.02; tobacco: p=0.02), respectively. Gene polymorphisms of CCL5-28, CCL5-403, and CCR5 play an important factor for the susceptibility of HCC, respectively. The synergic effects of these two gene polymorphisms to tobacco or alcohol consumption significantly increase the risk to develop HCC.
本研究旨在评估 CCL5-28、CCL5-403 和 CCR5 基因多态性与肝细胞癌（HCC）易感性之间的关系。本研究共纳入 449 例受试者，包括 347 例健康对照和 102 例 HCC 患者，采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析这些两种多态性变异对 HCC 的影响。结果发现，CCL5-28 的 CG 杂合子（AOR=2.35；95%CI=1.27-4.33，p=0.006）、CCL5-403 的 AA 纯合子（AOR=5.18；95%CI=2.25-11.91，p=0.0001）和 CCR5 的 AA 纯合子（AOR=2.47；95%CI=1.24-4.90，p=0.009）与野生基因型相比，HCC 易感性与遗传多态性显著相关。在调整其他混杂因素后，还发现基因-基因多态性的协同作用增加了 CCL5-28 的 CG 或 GG 与 CCL-403 的 GA 或 AA 以及 CCR5 的 GA 或 AA 个体发生 HCC 的风险（AOR=3.42；95%CI=1.39-8.38，p=0.007），与 CCL5-28、CCL-403 和 CCR5 的野生基因型个体相比。此外，酒精或烟草消费增加了 CCL5-28 的 CG 杂合子（酒精：p=0.001；烟草：p=0.006）、AA 纯合子（酒精：p=0.0004；烟草：p≤0.0001）或 GA 杂合子（烟草：p=0.03）以及 CCL5-403 的 CCR5 的 AA 纯合子（酒精：p=0.02；烟草：p=0.02）发生 HCC 的风险。CCL5-28、CCL5-403 和 CCR5 的基因多态性分别是 HCC 易感性的重要因素。这两种基因多态性与烟草或酒精消费的协同作用显著增加了发生 HCC 的风险。
