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.

Telomere length and TERT polymorphisms as biomarkers in asbestos-related diseases

“… 46 Similarly, an Indian study reported that rs2736100 contributes to a poorer prognosis of glioma patients. 47 On the other hand, a Chinese study did not seem to validate the relationship between this polymorphism and a poor prognosis in papillary thyroid carcinoma. 48 It is essential to consider that the mentioned studies did not focus on MM and were not conducted on Caucasians, thus caution should be applied when interpreting the data.…”

Relationship between IDH1/2 and TERT promoter mutation and the prognosis of human glioma patients

“…TERT occurs widely in a variety of malignant tumors, is related to the prognosis of patients, 7 and is highly expressed in glioma tissues. 8 In this study, the gene mutation of IDH1/2 and TERT promoter region was sequenced, and the postoperative follow-up was carried out. The relationship between the gene mutation and the occurrence, development and prognosis of glioma, was examined to provide a theoretical basis, and possible therapeutic target, for the treatment of glioma.…”