title: MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population.
abstract: 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.
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Meng-Yun
authors.initials: MY
authors.lastname: Wang
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Jia
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: He
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Li-Xin
authors.initials: LX
authors.lastname: Qiu
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Meng-Hong
authors.initials: MH
authors.lastname: Sun
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors.forename: Ya-Jun
authors.initials: YJ
authors.lastname: Yang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors.forename: Jiu-Cun
authors.initials: JC
authors.lastname: Wang
authors.affiliation: Ministry of Education Key Laboratory of Contemporary Anthropology, State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China.|Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.affiliation: Department of Abdominal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Ya-Nong
authors.initials: YN
authors.lastname: Wang
authors.affiliation: Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China.|Duke Cancer Institute, Duke University Medical Center, Durham, NC, USA.
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Wei
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D002681:China / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C482775:MDM4 protein, human; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger
keywords: MDM4; case-control study; gastric adenocarcinoma; genetic susceptibility; polymorphism