SMYD3基因可变数目串联重复序列3/3多态性增加中国人群肝细胞癌的发病风险并提示预后不良。

The SMYD3 VNTR 3/3 polymorphism confers an increased risk and poor prognosis of hepatocellular carcinoma in a Chinese population.

作者信息

Li Rui-Dong, Tang Yan-Hua, Wang Hui-Li, Yang Dong, Sun Li-Jun, Li Wei

机构信息

Department of Oncology, Affiliated Hospital of Jining Medical University, Jining 272009, PR China.

出版信息

Pathol Res Pract. 2018 May;214(5):625-630. doi: 10.1016/j.prp.2018.04.005. Epub 2018 Apr 17.

DOI:10.1016/j.prp.2018.04.005

PMID:29691085

Abstract

OBJECTIVE

Hepatocellular carcinoma (HCC) is one of the most lethal human malignancies in China, and the genetic link of hepatocarcinogenesis remains to be defined. Thus, we explored the role of SET and myeloid translocation protein 8, Nervy, and DEAF1 (MYND) domain containing protein 3 (SMYD3) gene polymorphism on risk and prognosis of HCC.

METHODS

A total of 236 patients with HCC who received treatment in Affiliated Hospital of Jining Medical University for the first time and 230 healthy individuals were enrolled in the study. After DNA extraction for all the subjects, polymerase chain reaction (PCR) was used to amplify and sequence variable numbers of tandem repeat (VNTR) loci of SMYD3 gene. SMYD3 gene was genotyped and its frequency distribution was calculated. Age, education level, income, smoking and drinking history, HCC family history, tumor node metastasis (TNM) staging, maximum tumor diameter, lymph node metastasis (LNM) etc. were investigated. Correlation of SMYD3 gene polymorphism and other risk factors with the occurrence and prognosis of HCC was analyzed.

RESULTS

The family history of HCC, drinking history, cirrhosis, and HBV or/and HCV infection, SMYD3 VNTR 3/3 were more frequently observed in subjects with HCC. Patients with SMYD3 VNTR 3/3 genotype, drinking-history, family history of HCC, cirrhosis and hepatitis B virus (HBV), TNM staging, maximum tumor diameter, LNM were more vulnerable to HCC. Besides, patients with SMYD3 VNTR 3/3 genotype had lower 2- and 3-year survival rate. The COX regression analysis revealed that drinking history, family history of HCC, SMYD3 VNTR 3/3 genotype, TNM staging, and LNM were all related to the prognosis of HCC.

CONCLUSION

This study indicates that drinking history, family history of HCC and SMYD3 VNTR 3/3, TNM staging, maximum tumor diameter, LNM might be risk factors for HCC, and SMYD3 VNTR 3/3 might contribute to a lower 2- and 3-year survival rate of patients with HCC.

摘要

目的

肝细胞癌（HCC）是中国最致命的人类恶性肿瘤之一，肝癌发生的遗传联系仍有待明确。因此，我们探讨了含SET和髓系易位蛋白8、Nervy和DEAF1（MYND）结构域蛋白3（SMYD3）基因多态性对HCC风险和预后的作用。

方法

本研究纳入了236例首次在济宁医学院附属医院接受治疗的HCC患者和230例健康个体。对所有受试者进行DNA提取后，采用聚合酶链反应（PCR）扩增并测序SMYD3基因的可变数目串联重复序列（VNTR）位点。对SMYD3基因进行基因分型并计算其频率分布。调查年龄、教育程度、收入、吸烟和饮酒史、HCC家族史、肿瘤淋巴结转移（TNM）分期、最大肿瘤直径、淋巴结转移（LNM）等情况。分析SMYD3基因多态性及其他危险因素与HCC发生及预后的相关性。

结果

在HCC患者中，HCC家族史、饮酒史、肝硬化以及HBV或/和HCV感染、SMYD3 VNTR 3/3更为常见。具有SMYD VNTR 3/3基因型、饮酒史、HCC家族史、肝硬化和乙型肝炎病毒（HBV）、TNM分期、最大肿瘤直径、LNM的患者更容易患HCC。此外，具有SMYD3 VNTR 3/3基因型的患者2年和3年生存率较低。COX回归分析显示，饮酒史、HCC家族史、SMYD3 VNTR 3/3基因型、TNM分期和LNM均与HCC的预后相关。