Association of strong risk ofhTERTgene polymorphic variants to malignant glioma and its prognostic implications with respect to different histological types and survival of glioma cases

Background Germline genetic variants of human telomerase reverse transcriptase (hTERT) are known to predispose for various malignancies, including glioma. The present study investigated genetic variation ofhTERTT/G (rs2736100) andhTERTG/A (rs2736098) with respect to glioma risk. Methods Confirmed cases (n= 106) were tested against 210 cancer-free healthy controls by the polymerase chain reaction-restriction fragment length polymorphism technique for genotyping. Results Homozygous variant 'GG' genotype of rs2736100 frequency was > 4-fold significantly different in cases versus controls (39.6% 17.2%;p< 0.0001). Furthermore, variant 'G' allele was found to be significantly associated with cases (0.5 versus 0.2 in controls;p< 0.0001). Homozygous variant rs2736098 'AA' genotype (35.8% versus 23.8%) and allele 'A' (0.49 versus 0.34) showed a marked significant difference in cases and controls, respectively (p< 0.05). InhTERTrs2736100, the GG genotype significantly presented more in higher grades and GBM (p< 0.0001). Furthermore, the GG variant ofhTERTrs2736100 had a poor probability with respect to the overall survival of patients compared to TG and TT genotypes (log rankp= 0.03). Interestingly, two haplotypes ofhTERTrs2736100/rs2736098 were identified as GG and GA that conferred a > 3- and 5-fold risk to glioma patients respectively, where variant G/A haplotype was observed to have the highest impact with respect to glioma risk (p< 0.0001). Conclusions The results of the present study indicate thathTERTrs2736098 and rs2736100 variants play an important role in conferring a strong risk of developing glioma. Furthermore,hTERTrs2736100 GG variant appears to play a role in the bad prognosis of glioma patients. Haplotypes GG and GA could prove to be vital tools for monitoring risk in glioma patients.