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.

Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx

“…MDM4 polymorphisms have been reported to be associated with the risk of developing gastric cancer [23], prostate cancer [24], and SCCHN [7], as well as HPV16-related SCCOP [7,25]. Among the three MDM4 SNPs we studied, two [rs11801299 (NC_000001.10:g.204529084G>A) and rs10900598 (NC_000001.10:g.204525568G>T)] are located in the 3′-untranslated region (3′-UTR), whereas the other, rs1380576 (NC_000001.10:g.204488278G>C), is in the first intron.…”

Five MDM4 gene polymorphisms on cancer risk: An updated systematic review and meta-analysis

“…For polymorphisms of MDM4 gene (rs1380576, rs1563828, rs10900598, rs11801299, and rs4245739), a total of 15 articles (including 29 case–control studies) with 21,365 cases and 29,280 controls met the inclusion criteria. 9-23 A total of 14 studies were performed in Asians, 11 studies were performed in Caucasians, and four studies in Iranian-Azeri. Controls of 19 studies were population-based controls and 10 studies were hospital-based controls.…”

Plasticity of Tumor Suppressor Functionality of p53 Includes Potential Carcinogenesis in Terms of Subsequent Progression of the Malignant Transformation Event

“…MDM4 plays an important role in carcinogenesis and interacts with p53 [11]. Principles of action of a prime tumor suppressor gene and protein as p53 illustrate the dual and ambiguous roles of a guardian of the cellular genome in homeostatic control of normal cells to the progression of malignant transformation and progression of carcinogenesis within initially transformed malignant cells.…”