Oncotarget

Research Papers:

Association between the functional polymorphism Ile31Phe in the AURKA gene and susceptibility of hepatocellular carcinoma in chronic hepatitis B virus carriers

Zhiyu Bao, Lei Lu, Xinyi Liu, Bingqian Guo, Yun Zhai, Yuanfeng Li, Yahui Wang, Bobo Xie, Qian Ren, Pengbo Cao, Yuqing Han, Weihua Jia, Minshan Chen, Xinqiang Liang, Xuan Wang, Yi-Xin Zeng, Fuchu He, Hongxing Zhang, Ying Cui and Gangqiao Zhou _

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Oncotarget. 2017; 8:54904-54912. https://doi.org/10.18632/oncotarget.18613

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Abstract

Zhiyu Bao1,2,3,4,5,*, Lei Lu6,*, Xinyi Liu1,4,5,*, Bingqian Guo1,4,5,*, Yun Zhai1,4,5, Yuanfeng Li1,4,5, Yahui Wang1,4,5, Bobo Xie1,4,5, Qian Ren1,4,5, Pengbo Cao1,4,5, Yuqing Han1,4,5, Weihua Jia7,8, Minshan Chen9, Xinqiang Liang2, Xuan Wang6, Yi-Xin Zeng7,8, Fuchu He1,4,5, Hongxing Zhang1,4,5, Ying Cui2 and Gangqiao Zhou1,4,5,10

1State Key Laboratory of Proteomics, Beijing Proteome Research Center, Beijing Institute of Radiation Medicine, Beijing, China

2Guangxi Medical University, Nanning, China

3Affiliated Hospital of Jining Medical University, Jining, China

4National Engineering Research Center for Protein Drugs, Beijing, China

5National Center for Protein Sciences Beijing, Beijing, China

6Department of Surgical Oncology, Bayi Hospital Affiliated Nanjing University of Chinese Medicine, Jindu Hospital, Nanjing, China

7State Key Laboratory of Oncology in Southern China, Guangzhou, China

8Department of Experimental Research, Sun Yat-Sen University Cancer Center, Guangzhou, China

9Department of Hepatobiliary Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China

10Anhui Medical University, Hefei, Anhui, China

*These authors have contributed equally to this work

Correspondence to:

Gangqiao Zhou, email: [email protected]

Ying Cui, email: [email protected]

Hongxing Zhang, email: [email protected]

Keywords: hepatocellular carcinoma, hepatitis B virus, AURKA, polymorphism, susceptibility

Received: February 17, 2017    Accepted: May 22, 2017    Published: June 27, 2017

ABSTRACT

Aurora kinase A (AURKA) is a serine threonine kinase which affects chromosomal separation and mitotic spindle stability through interaction with the centrosome during mitosis. Two functional nonsynonymous polymorphisms of the AURKA gene (Ile31Phe and Val57Ile) have been reported recently. We analyzed the association between the two polymorphisms and risk of the occurrence of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) in the Guangxi population consisting of 348 patients with HCC and 359 control subjects, and then validated the significant association in the Guangdong population consisting of 440 cases and 456 controls. All of the participants were of Chinese origin and HBV carriers. The two polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay or Sequenom MassARRAY iPLEX platform. In the Guangxi population, carriers of the AURKA 31Phe allele (Ile/Phe + Phe/Phe) were significantly associated with decreased susceptibility to HBV-related HCC when compared with noncarriers (Ile/Ile) (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.46-0.86, P = 3.4 × 10-3). On the contrary, no significant association was found between Val57Ile and HBV-related HCC occurrence. The association of Ile31Phe with HBV-related HCC occurrence was confirmed in the Guangdong population (OR = 0.64, 95% CI = 0.49-0.83, P = 8.0 × 10-4). The pooled analysis gave a joint P value of 5.5 × 10-6 (joint OR = 0.63, 95% CI = 0.52-0.77). Our findings suggest that AURKA Ile31Phe may play a role in mediating the susceptibility to HBV-related HCC among Chinese.


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