Individual and combined effects of MDM2 SNP309 and TP53 Arg72Pro on breast cancer risk: an updated meta-analysis.

The tumor suppressor gene TP53 and its negative regulator murine double minute 2 are involved in multiple cellular pathways. Two potentially functional single nucleotide polymorphisms (SNPs) MDM2 SNP309 and TP53 R72P have been extensively investigated to be associated with breast cancer risk. However, the original studies as well as the subsequent meta-analysis, have yielded contradictory results for the individual effect of the two SNPs on breast cancer risk, plus that conflicting results also existed for the combined effects of MDM2 SNP309 and TP53 R72P on breast cancer risk. This meta-analysis aimed to clarify the individual and combined effects of these two genes on breast cancer risk. We performed a meta-analysis of publications with a total 9,563 cases and 9,468 controls concerning MDM2 SNP309 polymorphism and 19,748 cases and 19,962 controls concerning TP53 R72P. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. In overall meta-analysis, individuals with the MDM2 SNP309TG genotype were associated with a borderline higher breast cancer risk than those with TT genotype (OR = 1.11, 95 % CI: 1.00-1.24, P (heterogeneity) = 0.007), whereas the TP53 R72P CC or GC genotype had no effects on breast cancer risk. In the stratified analyses, a significant association between MDM2 SNP309 and breast cancer risk were observed in Asian, but null significant association between TP53 R72P and breast cancer risk were found even in various subgroups. Moreover, no significant combined effects of MDM2 SNP309 and TP53 R72P were observed on breast cancer risk. The borderline association between MDM2 SNP309 and breast cancer risk in overall analysis should be treated with caution, and no significant combined effects for the two SNPs on breast cancer risk suggested functional investigations warranted to explore the molecular mechanism of the TP53-MDM2 circuit genes.