MDM2 SNP309, gene-gene interaction, and tumor susceptibility: an updated meta-analysis

<p>Abstract</p> <p>Background</p> <p>The tumor suppressor gene <it>p53 </it>is involved in multiple cellular pathways including apoptosis, transcriptional control, and cell cycle regulation. In the last decade it has been demonstrated that the single nucleotide polymorphism (SNP) at codon 72 of the <it>p53 </it>gene is associated with the risk for development of various neoplasms. <it>MDM2 </it>SNP309 is a single nucleotide T to G polymorphism located in the <it>MDM2 </it>gene promoter. From the time that this well-characterized functional polymorphism was identified, a variety of case-control studies have been published that investigate the possible association between <it>MDM2 </it>SNP309 and cancer risk. However, the results of the published studies, as well as the subsequent meta-analyses, remain contradictory.</p> <p>Methods</p> <p>To investigate whether currently published epidemiological studies can clarify the potential interaction between <it>MDM2 </it>SNP309 and the functional genetic variant in <it>p53 </it>codon72 (Arg72Pro) and <it>p53 </it>mutation status, we performed a meta-analysis of the risk estimate on 27,813 cases with various tumor types and 30,295 controls.</p> <p>Results</p> <p>The data we reviewed indicated that variant homozygote 309GG and heterozygote 309TG were associated with a significant increased risk of all tumor types (homozygote comparison: odds ratio (OR) = 1.25, 95% confidence interval (CI) = 1.13-1.37; heterozygote comparison: OR = 1.10, 95% CI = 1.03-1.17). We also found that the combination of GG and Pro/Pro, TG and Pro/Pro, GG and Arg/Arg significantly increased the risk of cancer (OR = 3.38, 95% CI = 1.77-6.47; OR = 1.88, 95% CI = 1.26-2.81; OR = 1.96, 95% CI = 1.01-3.78, respectively). In a stratified analysis by tumor location, we also found a significant increased risk in brain, liver, stomach and uterus cancer (OR = 1.47, 95% CI = 1.06-2.03; OR = 2.24, 95%CI = 1.57-3.18; OR = 1.54, 95%CI = 1.04-2.29; OR = 1.34, 95%CI = 1.07-1.29, respectively). However, no association was seen between <it>MDM2 </it>SNP309 and tumor susceptibility in the stratified analysis by <it>p53 </it>mutation status (GG vs TT: OR = 1.17, 95% CI = 0.75-1.82 and TG vs TT: OR = 1.09, 95% CI = 0.89-1.34 for positive <it>p53 </it>mutation status; GG vs TT: OR = 0.95, 95% CI = 0.72-1.25 and TG vs TT: OR = 1.06, 95% CI = 0.85-1.30 for negative <it>p53 </it>mutation status).</p> <p>Conclusions</p> <p>The analyses indicate that <it>MDM2 </it>SNP309 serves as a tumor susceptibility marker, and that there is an association between <it>MDM2 </it>SNP309 and <it>p53 </it>Arg72Pro regarding tumor susceptibility. Further studies that take into consideration environmental stresses and functional genetic variants in the <it>p53</it>-<it>MDM2</it>-related genes are warranted.</p