©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
Relationships between cell cycle pathway gene polymorphisms and risk of hepatocellular carcinoma
Yue-Li Nan, Yan-Ling Hu, Zhi-Ke Liu, Fang-Fang Duan, Yang Xu, Shu Li, Ting Li, Da-Fang Chen, Xiao-Yun Zeng
Yue-Li Nan, Yang Xu, Shu Li, Ting Li, Xiao-Yun Zeng, Department of Epidemiology, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Yan-Ling Hu, Medical Scientific Research Centre, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Zhi-Ke Liu, Fang-Fang Duan, Da-Fang Chen, Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China
Xiao-Yun Zeng, Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Zeng XY designed the research; Xu Y, Li S and Li T collected the materials and clinical data; Liu ZK and Duan FF performed the majority of experiments; Chen DF conceived the experimental assays; Nan YL performed the experiments, analyzed the data and wrote the manuscript; Hu YL made critical revisions of the manuscript.
Supported by National Natural Science Foundation of China, No. 81360448; Natural Science Foundation of Guangxi, No. 2014GXNSFAA118139; Fund of Key Laboratory of High-Incidence-Tumor Prevention and Treatment (Guangxi Medical University), Ministry of Education, No. GK2015-ZZ03 and No. GK2014-ZZ03; and Guangxi Outstanding Teacher Training Project for Colleges.
Institutional review board statement: The study was approved by the ethical review committee of Guangxi Medical University.
Informed consent statement: All study participants provided informed written consent prior to study enrollment.
Conflict-of-interest statement: The authors have declared that they have no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Xiao-Yun Zeng, MD, PhD, Department of Epidemiology, School of Public Health, Guangxi Medical University, No. 22 Shuangyong Road, Nanning 530021, Guangxi Zhuang Autonomous Region, China. email@example.com
Telephone: +86-771-5358325 Fax: +86-771-5352523
Received: March 3, 2016
Peer-review started: March 7, 2016
First decision: April 14, 2016
Revised: April 29, 2016
Accepted: May 21, 2016
Article in press: May 23, 2016
Published online: June 28, 2016
AIM: To investigate the associiations between the polymorphisms of cell cycle pathway genes and the risk of hepatocellular carcinoma (HCC).
METHODS: We enrolled 1127 cases newly diagnosed with HCC from the Tumor Hospital of Guangxi Medical University and 1200 non-tumor patients from the First Affiliated Hospital of Guangxi Medical University. General demographic characteristics, behavioral information, and hematological indices were collected by unified questionnaires. Genomic DNA was isolated from peripheral venous blood using Phenol-Chloroform. The genotyping was performed using the Sequenom MassARRAY iPLEX genotyping method. The association between genetic polymorphisms and risk of HCC was shown by P-value and the odd ratio (OR) with 95% confidence interval (CI) using the unconditional logistic regression after adjusting for age, sex, nationality, smoking, drinking, family history of HCC, and hepatitis B virus (HBV) infection. Moreover, stratified analysis was conducted on the basis of the status of HBV infection, smoking, and alcohol drinking.
RESULTS: The HCC risk was lower in patients with the MCM4 rs2305952 CC (OR = 0.22, 95%CI: 0.08-0.63, P = 0.01) and with the CHEK1 rs515255 TC, TT, TC/TT (OR = 0.73, 95%CI: 0.56-0.96, P = 0.02; OR = 0.67, 95%CI: 0.46-0.97, P = 0.04; OR = 0.72, 95%CI: 0.56-0.92, P = 0.01, respectively). Conversely, the HCC risk was higher in patients with the KAT2B rs17006625 GG (OR = 1.64, 95%CI: 1.01-2.64, P = 0.04). In addition, the risk was markedly lower for those who were carriers of MCM4 rs2305952 CC and were also HBsAg-positive and non-drinking and non-smoking (P < 0.05, respectively) and for those who were carriers of CHEK1 rs515255 TC, TT, TC/TT and were also HBsAg-negative and non-drinking (P < 0.05, respectively). Moreover, the risk was higher for those who were carriers of KAT2B rs17006625 GG and were also HBsAg-negative (P < 0.05).
CONCLUSION: Of 12 cell cycle pathway genes, MCM4, CHEK1 and KAT2B polymorphisms may be associated with the risk of HCC.
Core tip: We analyzed the effects of polymorphisms of 12 cell cycle pathway genes on the risk of hepatocellular carcinoma (HCC) in a large population of 1019 HCC cases and 1138 controls. The results suggest that MCM4 rs2305952 CC and CHEK1 rs515255 TC, TT, TC/TT may be significantly associated with a decreased risk of HCC. KAT2B rs17006625 GG may increase the risk of HCC.