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

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 Confirme...

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Published in:The journal of gene medicine 2020-11, Vol.22 (11), p.e3260-n/a
Main Authors: Pandith, Arshad A., Wani, Zahoor A., Qasim, Iqbal, Afroze, Dil, Manzoor, Usma, Amin, Ina, Baba, Shahid M., Koul, Aabid, Anwar, Iqra, Mohammad, Fozia, Bhat, Abdul R., Shah, Parveen
Format: Article
Language:English
Subjects:
allele
Alleles
Brain cancer
Gene polymorphism
Gene therapy
Genetic diversity
genotype
Genotype & phenotype
Genotyping
germ line
glioblastoma
Glioma
Haplotypes
hTERT
Medical prognosis
Polymerase chain reaction
Restriction fragment length polymorphism
RNA-directed DNA polymerase
Survival
Telomerase
Telomerase reverse transcriptase
variant
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Summary: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. Germline variants of hTERT gene are known to confer risk to develop various malignancies, including glioma. hTERT rs2736100 ‘GG' significantly differed in cases versus controls (39.6% 17.2%; p < 0.0001/G allele (0.5 versus 0.2 in controls, p < 0.0001). GG significantly presented more in higher grades/GBM (p < 0.0001). hTERT variant rs2736098 ‘AA’ genotype (35.8% versus 23.8%) and allele ‘A’ (0.49 versus 0.34) showed significant difference in cases and controls (p < 0.05). GG variant of hTERT rs2736100 had poor probability in overall survival of patients (log rank p = 0.03). Haplotypes GG and GA conferred a > 3‐ and 5‐fold risk to glioma patients
ISSN:1099-498X
1521-2254
DOI:10.1002/jgm.3260