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Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India
BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506276/ https://www.ncbi.nlm.nih.gov/pubmed/37718447 http://dx.doi.org/10.1186/s12885-023-11387-z |
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author | Bhat, Gh. Rasool Jamwal, Rajeshwer Singh Sethi, Itty Bhat, Amrita Shah, Ruchi Verma, Sonali Sharma, Minerva Sadida, Hana Q. Al-Marzooqi, Sara K. Masoodi, Tariq Mirza, Sameer Haris, Mohammad Macha, Muzafar A. Akil, Ammira S. Alshabeeb Bhat, Ajaz A. Kumar, Rakesh |
author_facet | Bhat, Gh. Rasool Jamwal, Rajeshwer Singh Sethi, Itty Bhat, Amrita Shah, Ruchi Verma, Sonali Sharma, Minerva Sadida, Hana Q. Al-Marzooqi, Sara K. Masoodi, Tariq Mirza, Sameer Haris, Mohammad Macha, Muzafar A. Akil, Ammira S. Alshabeeb Bhat, Ajaz A. Kumar, Rakesh |
author_sort | Bhat, Gh. Rasool |
collection | PubMed |
description | BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11387-z. |
format | Online Article Text |
id | pubmed-10506276 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-105062762023-09-19 Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India Bhat, Gh. Rasool Jamwal, Rajeshwer Singh Sethi, Itty Bhat, Amrita Shah, Ruchi Verma, Sonali Sharma, Minerva Sadida, Hana Q. Al-Marzooqi, Sara K. Masoodi, Tariq Mirza, Sameer Haris, Mohammad Macha, Muzafar A. Akil, Ammira S. Alshabeeb Bhat, Ajaz A. Kumar, Rakesh BMC Cancer Research BACKGROUND: Telomeres are repetitive DNA sequences located at the ends of chromosomes, playing a vital role in maintaining chromosomal integrity and stability. Dysregulation of telomeres has been implicated in the development of various cancers, including non-small cell lung cancer (NSCLC), which is the most common type of lung cancer. Genetic variations within telomere maintenance genes may influence the risk of developing NSCLC. The present study aimed to evaluate the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India, and to investigate the relationship between telomere length and NSCLC risk. METHODS: We employed the cost-effective and high-throughput MassARRAY MALDI-TOF platform to assess the genetic associations of select variants within telomere maintenance genes in a population from Jammu and Kashmir, North India. Additionally, we used TaqMan genotyping to validate our results. Furthermore, we investigated telomere length variation and its relation to NSCLC risk in the same population using dual-labeled fluorescence-based qPCR. RESULTS: Our findings revealed significant associations of TERT rs10069690 and POT1 rs10228682 with NSCLC risk (adjusted p-values = 0.019 and 0.002, respectively), while TERF2 rs251796 and rs2975843 showed no significant associations. The TaqMan genotyping validation further substantiated the associations of TERT rs10069690 and rs2242652 with NSCLC risk (adjusted p-values = 0.02 and 0.003, respectively). Our results also demonstrated significantly shorter telomere lengths in NSCLC patients compared to controls (p = 0.0004). CONCLUSION: This study highlights the crucial interplay between genetic variation in telomere maintenance genes, telomere attrition, and NSCLC risk in the Jammu and Kashmir population of North India. Our findings suggest that TERT and POT1 gene variants, along with telomere length, may serve as potential biomarkers and therapeutic targets for NSCLC in this population. Further research is warranted to elucidate the underlying mechanisms and to explore the potential clinical applications of these findings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-11387-z. BioMed Central 2023-09-18 /pmc/articles/PMC10506276/ /pubmed/37718447 http://dx.doi.org/10.1186/s12885-023-11387-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Bhat, Gh. Rasool Jamwal, Rajeshwer Singh Sethi, Itty Bhat, Amrita Shah, Ruchi Verma, Sonali Sharma, Minerva Sadida, Hana Q. Al-Marzooqi, Sara K. Masoodi, Tariq Mirza, Sameer Haris, Mohammad Macha, Muzafar A. Akil, Ammira S. Alshabeeb Bhat, Ajaz A. Kumar, Rakesh Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India |
title | Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India |
title_full | Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India |
title_fullStr | Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India |
title_full_unstemmed | Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India |
title_short | Associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the Jammu and Kashmir population of North India |
title_sort | associations between telomere attrition, genetic variants in telomere maintenance genes, and non-small cell lung cancer risk in the jammu and kashmir population of north india |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10506276/ https://www.ncbi.nlm.nih.gov/pubmed/37718447 http://dx.doi.org/10.1186/s12885-023-11387-z |
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