Association between epidermal growth factor gene +61A/G polymorphism and the risk of hepatocellular carcinoma: a meta-analysis based on 16 studies.
BACKGROUND
The association between epidermal growth factor (EGF) gene +61A/G polymorphism (rs4444903) and hepatocellular carcinoma (HCC) susceptibility has been widely reported, but the results were inconsistent. To clarify the effect of this polymorphism on HCC risk, a meta-analysis was performed.


METHODS
The PubMed, Embase, Cochrane Library, Web of Science, Chinese BioMedical Literature (CBM), Wanfang and Chinese National Knowledge Infrastructure (CNKI) databases were systematically searched to identify relevant studies published up to December 2013. Data were extracted independently by two authors. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated to assess the strength of association.


RESULTS
A total of 16 studies including 2475 HCC cases and 5381 controls were included in this meta-analysis. Overall, a significantly increased HCC risk was observed under all genetic models (G vs. A: OR = 1.383, P < 0.001, 95% CI: 1.174-1.629; GG vs. GA + AA: OR = 1.484, P < 0.001, 95% CI: 1.198-1.838; GG + GA vs. AA: OR = 1.530, P < 0.001, 95% CI: 1.217-1.924; GG vs. AA: OR = 1.958, P < 0.001, 95% CI: 1.433-2.675; GA vs. AA: OR = 1.215, P = 0.013, 95% CI: 1.041-1.418). In the subgroup analyses by ethnicity, a significant association with HCC risk was found in Asian populations (G vs. A: OR = 1.151, P = 0.001, 95% CI: 1.056-1.255), European populations (G vs. A: OR = 1.594, P = 0.027, 95% CI: 1.053-2.413, and African populations (G vs. A: OR = 3.599, P < 0.001, 95% CI: 2.550-5.080), respectively.


CONCLUSIONS
Our study shows that EGF +61A/G polymorphism is significantly associated with the increased HCC risk, especially in Asian populations. Further large-scale and well-designed studies are required to confirm this conclusion.
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. jiangguoping@zju.edu.cn.|Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Hangzhou, China. jiangguoping@zju.edu.cn.
Guoping
G
Jiang
Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang, 310029, China. yuke2009@gmail.com.
Ke
K
Yu
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. lfshao@hotmail.com.
Lifang
L
Shao
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. yuxb@zju.edu.cn.|Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Hangzhou, China. yuxb@zju.edu.cn.
Xiaobo
X
Yu
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. huchen@outlook.com.
Chen
C
Hu
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. cxqp1212@126.cm.|Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Hangzhou, China. cxqp1212@126.cm.
Pei
P
Qian
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. xiehy@zju.edu.cn.|Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Hangzhou, China. xiehy@zju.edu.cn.
Haiyang
H
Xie
State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai, China. lijj64@gmail.com.
Jinjun
J
Li
Zhejiang-California International Nanosystems Institute, Zhejiang University, Hangzhou, Zhejiang, 310029, China. zhengjie20141@163.com.
Jie
J
Zheng
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Rd, Hangzhou, 310003, China. shusenzheng@zju.edu.cn.|Key Laboratory of Combined Multi-organ Transplantation of Ministry of Public Health, Hangzhou, China. shusenzheng@zju.edu.cn.
Shusen
S
Zheng
D044466:Asian People; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D004815:Epidermal Growth Factor / Q000235:genetics*; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D044465:White People
D004815:Epidermal Growth Factor