Wang Baoyan, Xu Peijuan, Shu Qing, Yan Simin, Xu Hang
Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China.
Nanjing Tongren Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, China.
Clin Appl Thromb Hemost. 2021 Jan-Dec;27:10760296211031291. doi: 10.1177/10760296211031291.
Venous thromboembolism (VTE) is a common and potentially fatal complication in cancer patients. Although several genetic risk factors related to thrombophilia have been identified, their contributions for the occurrence of VTE in cancer patients have conflicting results. The aim of this study was to evaluated the gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T and plasminogen activator inhibitor-1 (PAI-1) 4G/5G in lung cancer patients, with and without VTE, and the combined effect on the risk of VTE. 92 lung cancer patients diagnosed with VTE (VTE group) and 122 lung cancer patients without VTE (non-VTE group) were enrolled in the study. The gene polymorphisms were analyzed by the method of polymerase chain reaction-restriction fragment length polymorphism. Gene mutation of factor V Leiden was not detected both in non-VTE group and VTE group. The frequency of MTHFR C677T homozygous mutation in VTE group was 25.00%, higher than that in the non-VTE group without statistical difference. It was found that the PAI-1 4G4G genotype is associated with a higher risk of VTE (OR: 2.62, 95%CI: 1.19-5.75). Interestingly, the interaction between MTHFR C677T and PAI-1 4G/5G polymorphisms showed that the coexistence of the 2 homozygous mutation could further increase the risk of VTE. In conclusion, PAI-1 4G/5G polymorphism may be an increased risk factor for VTE among lung cancer patients in Chinese population. The homozygous MTHFR C677T mutation may be not a risk factor for VTE but increases the risk, accompanied with PAI-1 4G5G genotype.
静脉血栓栓塞症（VTE）是癌症患者中一种常见且可能致命的并发症。尽管已经确定了几种与血栓形成倾向相关的遗传风险因素，但它们在癌症患者VTE发生中的作用结果相互矛盾。本研究的目的是评估肺癌患者中伴有和不伴有VTE的亚甲基四氢叶酸还原酶（MTHFR）C677T和纤溶酶原激活物抑制剂-1（PAI-1）4G/5G的基因多态性，以及对VTE风险的联合影响。本研究纳入了92例诊断为VTE的肺癌患者（VTE组）和122例无VTE的肺癌患者（非VTE组）。采用聚合酶链反应-限制性片段长度多态性方法分析基因多态性。在非VTE组和VTE组中均未检测到因子V莱顿基因突变。VTE组中MTHFR C677T纯合突变频率为25.00%，高于非VTE组，但无统计学差异。发现PAI-1 4G4G基因型与较高的VTE风险相关（OR：2.62，95%CI：1.19-5.75）。有趣的是，MTHFR C677T与PAI-1 4G/5G多态性之间的相互作用表明，两种纯合突变共存可进一步增加VTE风险。总之，PAI-1 4G/5G多态性可能是中国人群肺癌患者VTE风险增加的一个因素。MTHFR C677T纯合突变可能不是VTE风险因素，但与PAI-1 4G5G基因型一起会增加VTE风险。
