MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population
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Meng-Yun Wang1,2, Ming Jia1,2, Jing He1,2, Fei Zhou1,2, Li-Xin Qiu1,3, Meng-Hong Sun4, Ya-Jun Yang5,6, Jiu-Cun Wang5,6, Li Jin5,6, Ya-Nong Wang7, Qing-Yi Wei1,8
1Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
3Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
4Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
5Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
6Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
7Department of Abdominal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
8Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA
Ya-Nong Wang, email: [email protected]
Qing-Yi Wei, email: [email protected]
Keywords: Case-control study, gastric adenocarcinoma, genetic susceptibility, MDM4, polymorphism
Received: May 06, 2016 Accepted: November 11, 2016 Published: January 14, 2017
MDM4 is a p53-interacting protein and plays an important role in carcinogenesis. In this study of 1,077 gastric cancer (GCa) cases and 1,173 matched cancer-free controls, we investigated associations between three tagging single nucleotide polymorphisms (SNPs) (rs11801299 G>A, rs1380576 C>G and rs10900598 G>T) in MDM4 and gastric cancer risk in an Eastern Chinese Population. In logistic regression analysis, a significantly decreased GCa risk was associated with the rs1380576 GG variant genotype (adjusted odds ratio [OR] =0.74, 95% confidence interval [CI] =0.56-0.98) under a recessive model, which remained significant after correction by the false-positive reporting probability. This risk was more evident in subgroups of older subjects, males, never smokers, never drinkers and cancers of non-cardia. We then performed SNP-mRNA expression correlation analysis and found that the GG variant genotype was associated with significantly decreased expression of MDM4 mRNA in normal cell lines for 44 Chinese (P=0.032 for GG vs. CC) as well as for 269 multi-ethnic subjects (P<0.0001 for GG vs. CC). Our results suggest that the MDM4 rs1380576 G variant may be markers for GCa susceptibility. Larger, independent studies are warranted to validate our findings.
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