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 5 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 5 0.5, 95% CI 0.4-0.8 and OR 5 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 5 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 5 1.5, 95% CI 1.1-1.9 and OR 5 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. ' 2005 Wiley-Liss, Inc.

Association between p53 Gene Variants and Oral Cancer Susceptibility in Population from Gujarat, West India

“…Odds ratios (ORs) and 95% Confidence Intervals (CIs) were calculated for the risk estimation of oral cancer development. The highest proportion of a homozygous genotype at any particular p53 locus in the control group was considered as referent genotype to estimate risk associated with these polymorphisms (Mitra et al, 2005). Linkage disequilibrium analysis was performed for the study groups.…”

“…Among them, most of reports are on Arg72Pro polymorphism of p53 gene. There is only one study from eastern region of India, explored the role of these three polymorphisms in oral cancer (Mitra et al, 2005). They have observed that the Proline allele was more frequent in control population and no association was found between oral cancer risk and Arg72Pro polymorphism.…”

“…The results of intron 3 and intron 6 polymorphisms are also inconsistent and ranges from no association to increased risk in different population (Wang-Gohrke et al, 1999;Wu et al, 2002;Sprague et al, 2007;Gallì et al, 2009;Hrstka et al, 2009;Hu et al, 2010). From India, only one study from east region has analyzed the association between intron 3 and intron 6 polymorphisms in oral cancer risk, suggested no association between intron 3 polymorphism and oral cancer risk, however, A allele at intron 6 was protective for oral cancer development (Mitra et al, 2005). This is the first study from this region which has analyzed association of these intronic polymorphisms and oral cancer risk.…”

“…It was also found that tobacco users who were carriers of Pro allele at exon 4 locus may be protected from oral cancer development. However, the only study from India failed to observe any association between Arg72Pro polymorphism and oral cancer development in tobacco users (Mitra et al, 2005). They have suggested that combination of A/A and A/G genotypes at intron 6 locus showed protective effect towards oral cancer development but at a low smoking dose.…”

“…This fact is very crucial for country like, India where wide variations in ethnicity and life style exist. There is a single study from east region of India, analyzed association between these three polymorphisms and oral cancer till date (Mitra et al, 2005). It has also been reported that the frequencies of the polymorphisms tend to differ among Indians and this is mainly due to differences in ethnicity (Mitra et al, 2003).…”