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

ABSTRACT

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 of hTERT T/G (rs2736100) and hTERT G/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). In hTERT rs2736100, the GG genotype significantly presented more in higher grades and GBM (p < 0.0001). Furthermore, the GG variant of hTERT rs2736100 had a poor probability with respect to the overall survival of patients compared to TG and TT genotypes (log rank p = 0.03). Interestingly, two haplotypes of hTERT rs2736100/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 that hTERT rs2736098 and rs2736100 variants play an important role in conferring a strong risk of developing glioma. Furthermore, hTERT rs2736100 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.