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.