Impact of MDM2 SNP309T>G polymorphism: Increased risk of developing non small cell lung cancer and poor prognosis in indian patients

Jamsheed Javid, Rashid Mir, M. Masroor, Shazia Farooq, Imtiyaz Ahamad, Prasant Yadav, Maryam Zubari, Pc Ray, Ajaz Ahmad Bhat, Pk Julka, Anant Mohan, Maqbool Lone, Ma Banday, Alpana Saxena

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Abstract

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.

Original languageEnglish
Pages (from-to)341-346
Number of pages6
JournalJournal of Cancer Science and Therapy
Volume4
Issue number10
DOIs
Publication statusPublished - 19 Nov 2012
Externally publishedYes

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Keywords

  • Allele specific oligonucleotide
  • Amplification refractory mutation system
  • MDM2
  • Non small cell lung cancer
  • SNP309T>G polymorphism
  • Tetra-primer ARMS-PCR and ASO-PCR

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Javid, J., Mir, R., Masroor, M., Farooq, S., Ahamad, I., Yadav, P., Zubari, M., Ray, P., Bhat, A. A., Julka, P., Mohan, A., Lone, M., Banday, M., & Saxena, A. (2012). Impact of MDM2 SNP309T>G polymorphism: Increased risk of developing non small cell lung cancer and poor prognosis in indian patients. Journal of Cancer Science and Therapy, 4(10), 341-346. https://doi.org/10.4172/1948-5956.1000165