TP53 polymorphisms in gliomas from Indian patients: Study of codon 72 genotype, rs1642785, rs1800370 and 16 base pair insertion in intron-3

Several single nucleotide polymorphisms of the TP53 gene have been reported, amongst which polymorphism in codon 72 (rs1042522) has received significant attention and shown to be associated with disease susceptibility in different cancer types. However, there are variable reports on this polymorphism in gliomas from worldwide with inconsistent results. In addition, the implications of other polymorphic loci are not much explored in gliomas. Hence, in the present study the TP53 sequence was analyzed for all polymorphism and mutations in a total of 84 gliomas of different types and grades from patients of Indian origin. The complete sequence of all coding exons (2 to 11) and introns 2, 3, 5 and 8 of TP53 gene were studied while for introns 1, 4, 6, 7, 9 and 10, only exon flanking regions could be studied. The polymorphic loci were compared with control population. In addition to the well known codon 72 polymorphism (rs1042522), three other polymorphisms rs1642785, rs1800370 and a 16 base pair insertion in intron-3 were found. At codon 72, our study showed higher Arg/Arg genotype in gliomas compared to normal population (38% versus 13%). The Arg allele frequency in glioma patients was comparatively higher than controls (0.55 versus 0.45; P=0.037). The Arg allele frequency was also high in adult glioblastomas compared to paediatric counterparts (0.55 versus 0.36). However, there was no significant association of TP53 mutations with any genotype of codon 72. At rs1642785, the G allele frequency was significantly higher in gliomas than in control population (0.55 versus 0.36, P=0.005). The genotype at a 16 base pair insertion in intron-3 was almost similar in case and control. However, the polymorphism at rs1800370 was exclusive to gliomas. This is the first report of TP53 gene polymorphism in glioma patients from India. Our study also delineates the frequency of four polymorphisms in gliomas for the first time. The codon 72 variant (rs1042522) and rs1642785 polymorphisms possibly poses risk to glioma development in Indian population. However, the functional significance of these polymorphism needs further elucidation.