MDM4 rs4245739 A > C polymorphism correlates with reduced overall cancer risk in a meta-analysis of 69477 subjects.
Mouse double minute 4 (MDM4) is a p53-interacting oncoprotein that plays an important role in the p53 tumor suppressor pathway. The common rs4245739 A > C polymorphism creates a miR-191 binding site in the MDM4 gene transcript. Numerous studies have investigated the association between this MDM4 polymorphism and cancer risk, but have failed to reach a definitive conclusion. To address this issue, we conducted a meta-analysis by selecting eligible studies from MEDLINE, EMBASE, and Chinese Biomedical databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. We also performed genotype-based mRNA expression analysis using data from 270 individuals retrieved from public datasets. A total of 15 studies with 19796 cases and 49681 controls were included in the final meta-analysis. The pooled results revealed that the MDM4 rs4245739C allele is associated with a decreased cancer risk in the heterozygous (AC vs. AA: OR = 0.82, 95% CI = 0.73-0.93), dominant (AC/CC vs. AA: OR = 0.82, 95% CI = 0.72-0.93), and allele contrast models (C vs. A: OR = 0.84, 95% CI = 0.76-0.94). The association was more prominent in Asians and population-based studies. We also found that the rs4245739C allele was associated with decreased MDM4 mRNA expression, especially for Caucasians. Thus the MDM4 rs4245739 A > C polymorphism appears to be associated with decreased cancer risk. These findings would be strengthened by new studies with larger sample sizes and encompassing additional ethnicities.
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
Chaoyi
C
Xu
Molecular Epidemiology Laboratory and Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
Jinhong
J
Zhu
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Wen
W
Fu
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
Zongwen
Z
Liang
Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Shujie
S
Song
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
Yuan
Y
Zhao
Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
Lihua
L
Lyu
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
Anqi
A
Zhang
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.|Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Jing
J
He
Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
Ping
P
Duan
D018797:Cell Cycle Proteins; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000209:etiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D017594:Publication Bias; D012333:RNA, Messenger / Q000032:analysis; D012306:Risk
D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger
MDM4; cancer susceptibility; meta-analysis; polymorphism
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