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