Polymorphisms at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer.
Polymorphisms at loci controlling cellular processes such as cell cycle, DNA repair, and apoptosis may modulate 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 (OR = 1.6, 95% CI = 1.1-2.3) and oral cancer (OR = 2.4, 95% CI = 1.7-3.3) 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 not modified 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 (OR = 3.0, 95% CI = 1.3-7.0) 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.
Misra
Chaitali
C
Molecular & Human Genetics Division, Indian Institute of Chemical Biology, Kolkata 700 032, India.
Majumder
Mousumi
M
Bajaj
Swati
S
Ghosh
Saurabh
S
Roy
Bidyut
B
Roychoudhury
Susanta
S
D000328:Adult; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007971:Leukoplakia / Q000209:etiology / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000209:etiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014030:Tobacco, Smokeless / Q000009:adverse effects; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2