MDM2 promoter polymorphism (rs2279744) and serum estrogen level are associated with increased risk of epithelial ovarian cancer: A case-control study

Introduction: Epithelial ovarian cancer (EOC) is most common malignancy affecting Indian women. One of the transcriptional targets of p53 is human homolog of Murine Double Minute 2 Oncogene (MDM2) which is a crucial negative regulator of p53. Polymorphism in intronic promoter P2 region of MDM2 at position 309 increase binding affinity of specific protein 1, lead to over expression of MDM2 and deflation of p53 pathway. The objectives of study were to find effect of MDM2 SNP309 T>G polymorphism and serum estrogen level on risk of development of EOC and interaction between MDM2 SNP309 T>G and TP53 72 Arg>Pro polymorphism. Materials and Methods: Eighty EOC cases and eighty age matched healthy controls were included in study. MDM2 SNP309 T>G polymorphism was detected by ASO-PCR technique and serum estrogen levels were detected by chemiluminescence immunoassay. Result: MDM2 SNP309 GG genotype was associated with significantly increased risk (OR: 2.86, 95%, CI: 1.07-7.66; P=0.03) and early age onset (P=0.001) of EOC. Serum Estrogen was significantly (P<0>G and TP53 72Arg>Pro gene polymorphism act additively in developing ovarian cancer. Conclusion: This study provides evidence that MDM2 SNP309 T>G promoter polymorphism in association with the higher serum estrogen levels is associated with genetic susceptibility and early age onset of ovarian cancer.