Dataset Information

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.

SUBMITTER: Wang MY

PROVIDER: S-EPMC5386704 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population.

Wang Meng-Yun MY Jia Ming M He Jing J Zhou Fei F Qiu Li-Xin LX Sun Meng-Hong MH Yang Ya-Jun YJ Wang Jiu-Cun JC Jin Li L Wang Ya-Nong YN Wei Qing-Yi QY

Oncotarget 20170301 12

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 ...[more]

PMID: 28099948

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Project description:PurposePrevious studies showed that peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator1 family (PPARGC1A and PPARGC1B) gene single nucleotide variants (SNVs)were strongly associated with cancer susceptibility. The purpose of this study was to investigate the association of PPARγ, PPARGC1A, and PPARGC1B variants with the risk of gastric cancer (GC).Patients and methodsWe performed a case-control study of 490 GC cases and 1,476 healthy controls from eastern China. PPARγ rs1801282 C > G, rs3856806 C > T, PPARGC1A rs2970847 C > T, rs8192678 C > T and PPARGC1B rs7732671 G > C, rs17572019 G > A SNVs were selected to investigate the association between these SNVs and GC susceptibility. Genotypes of the SNVs were assessed by multiplex fluorescent PCR using a custom-by-design 48-Plex SNPscantm Kit.ResultsThe PPARγ rs1801282 SNV was associated with a decreased risk for GC (GC vs. CC: odds ratio (OR) = 0.62, 95% confidence interval (95%CI) = 0.42-0.93, adjusted P = 0.019; GC + GG vs. GG: OR = 0.63 95%CI = 0.42-0.93, adjusted P = 0.019; respectively). In addition, stratified analysis revealed that the PPARγ rs1801282 SNV was correlated with the risk of GC in subgroups of age ≥ 61, no smoking, and no alcohol consuming. We also confirmed that the PPARγ rs3856806 C > T SNV promoted the risk of GC in women. The PPARGC1A rs8192678 TT genotype decreased the susceptibility of GC in men. The PPARGC1A rs2970847 C > T SNV decreased the susceptibility of GC in the subgroup of BMI ≥ 24 kg/m2. The PPARGC1B rs7732671 G > C and rs17572019 G > A SNVs promoted the risk of GC in the subgroup of BMI ≥ 24 kg/m2.ConclusionThis study indicates that the PPARγ, PPARGC1A, and PPARGC1B SNVs may be associated with the susceptibility of GC in eastern Chinese population. Future studies with larger populations, detailed H. pylori infection status for subgroup analysis, and functional study are needed to further clarify the relationship between these SNVs and GC risk.

Dataset Information

MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population.

Publications

MDM4 genetic variants and risk of gastric cancer in an Eastern Chinese population.

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