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Polymorphisms at p53, p73, and MDM2 Loci Modulate the Risk of Tobacco Associated Leukoplakia and Oral Cancer

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Title Polymorphisms at p53, p73, and MDM2 Loci
Modulate the Risk of Tobacco Associated
Leukoplakia and Oral Cancer
 
Creator Misra, Chaitali
Majumder, Mousumi
Bajaj, Swati
Ghosh, Saurabh
Roy, Bidyut
Roychoudhury, Susanta
 
Subject Molecular & Human Genetics
 
Description Polymorphisms at loci controlling cellular processes such as cell cycle, DNA repair, and apoptosismaymodulate the risk
of cancer. We examined the association of two linked polymorphisms (G4C14–A4T14) at p73 and one polymorphism
(309G>T) at MDM2 promoter with the risk of leukoplakia and oral cancer. The p73 and MDM2 genotypes were
determined in 197 leukoplakia patients, 310 oral cancer patients and in 348 healthy control subjects. The p73 GC/AT
genotype increased the risk of leukoplakia (OR¼1.6, 95% CI¼1.1–2.3) and oral cancer (OR¼2.4, 95% CI¼1.7–3.3)
but the 309G>T MDM2 polymorphism independently could not modify the risk of any of the diseases. Stratification of
the study population into subgroups with different tobacco habits showed that the risk of the oral cancer is notmodified
further for the individuals carrying p73 risk genotype. However, leukoplakia patients with smokeless tobacco habit
showed increased risk with combined GC/AT and AT/AT (OR¼3.0, 95%CI¼1.3–7.0) genotypes. A combined analysis
was done with our previous published data on p53 codon 72 pro/arg polymorphism. Analysis of pair wise genotype
combinations revealed increase in risk for specific p73-MDM2 and p73-p53 genotype combinations. Finally, the
combined three loci analyses revealed that the presence of at least one risk allele at all three loci increases the risk
of both leukoplakia and oral cancer. � 2009 Wiley-Liss, Inc.
 
Publisher John Wiley & Sons
 
Date 2009
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/246/1/MOLECULAR_CARCINOGENESIS%2C48(9)%2C790%2D800%2C2009[26].pdf
Misra, Chaitali and Majumder, Mousumi and Bajaj, Swati and Ghosh, Saurabh and Roy, Bidyut and Roychoudhury, Susanta (2009) Polymorphisms at p53, p73, and MDM2 Loci Modulate the Risk of Tobacco Associated Leukoplakia and Oral Cancer. Molecular Carcinogenesis, 48 (9). pp. 790-800. ISSN 0899-1987
 
Relation http://dx.doi.org/10.1002/mc.20523
http://www.eprints.iicb.res.in/246/