Impact of MDM2 SNP309T>G Polymorphism: Increased Risk of Developing Non Small Cell Lung Cancer and Poor Prognosis in Indian Patients
- *Corresponding Author:
- Alpana Saxena
Director, Professor and Head
Department of Biochemistry
Maulana Azad Medical College and Associated Hospitals
New Delhi 110002, India
E-mail: [email protected],
Received date: August 16, 2012; Accepted date: September 22, 2012; Published date: September 24, 2012
Citation: Javid J, Rashid Mir AB, Ahamad I, Farooq S, Yadav P, et al. (2012) Impact of MDM2 SNP309T>G Polymorphism: Increased Risk of Developing Non Small Cell Lung Cancer and Poor Prognosis in Indian Patients. J Cancer Sci Ther 4: 341-346. doi: 10.4172/1948-5956.1000165
Copyright: © 2012 Javid J, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Background: MDM2 is an important negative regulator of the TP53 pathway, over expressed in many cancers as oncoprotein. Polymorphisms in the promoter region of the MDM2 gene have been shown to alter protein expression and may, thus play an important role in carcinogenesis.
Aim and methods: To test our hypothesis that the MDM2 promoter polymorphisms are associated with risk of non small cell lung cancer, we conducted a hospital-based, case–control study of 136 Indian patients diagnosed with NSCLC and 136 cancer-free controls and investigated the association between genetic variation in the promoter region of MDM2 (c.–51309G4T, rs2279744:g.G4T) and the risk of developing NSCLC by tetra-primer ARMS-PCR and ASO-PCR.
Results: Compared with the MDM2-2580TT genotype, we found that the MDM2-309G variant genotypes were associated with an increased risk of NSCLC in Indian patients [OR 3.88 (1.82-8.27) RR 1.94 (1.27-2.96) RD 32.6 (15.7-49.6) p 0.0004 for GG and OR 2.60 (1.49-4.57) RR 1.52 (1.20-1.93) RD 23.16 (10.3-36.0) p 0.0009 for GT genotype]. GG genotype was found to be associated with poor survival outcome of NSCLC patients and in addition significant association was observed with stage (p 0.01) and metastasis status (p 0.002) of NSCLC patients.
Conclusion: Genetic polymorphism in cell cycle regulatory genes MDM2 contribute to the risk of developing NSCLC in Indian Patients. In addition G allele was associated with an increased risk and poor survival outcome than T allele.