Risk assessment of p53 genotypes and haplotypes in tobacco-associated leukoplakia and oral cancer patients from eastern India

Abstract

The role of 3 p53 polymorphisms (16 bp duplication at intron 3, codon 72 Arg/Pro and intron 6 NciI RFLP at np 13494) as potential markers for indicating cancer risk remains inconclusive. In our case-control study consisting of 197 leukoplakia and 310 oral squamous cell carcinoma (SCC) patients and 348 controls, genotype frequencies at these 3 p53 loci were determined by PCR-RFLP method and analyzed by multiple logistic regression to determine the risks of the diseases. The 2/2 genotype at codon 72 of p53 was at risk for developing leukoplakia (OR = 1.6, 95% CI 1.1–2.3), whereas the combination of 1/2 and 2/2 genotypes at intron 3 and 1/1 and 1/2 genotypes at intron 6 conferred a protective effect against leukoplakia and oral SCC development, respectively (OR = 0.5, 95% CI 0.4–0.8 and OR = 0.6, 95% CI 0.5–0.9, respectively). When subjects were stratified according to specific tobacco habit, the risk/protection estimates improved significantly in some cases. Specifically, the exclusive smokers with p53 codon 72 2/2 genotype showed a higher risk of developing leukoplakia (OR = 2.7, 95% CI 1.2–6.3). Furthermore, a particular p53 haplotype 1-2-2 was at risk for both tobacco-associated leukoplakia and oral SCC (OR = 1.5, 95% CI 1.1–1.9 and OR = 1.3, 95% CI 1.1–1.7, respectively). Our results show that both specific p53 genotype and haplotype can indicate risk of tobacco-associated leukoplakia, but risk of development of tobacco-associated oral SCC can be predicted by specific p53 haplotype only.