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PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer
About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair an...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795517/ https://www.ncbi.nlm.nih.gov/pubmed/36590386 http://dx.doi.org/10.3389/pore.2022.1610751 |
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author | Wang, Hetong Xie, Haitao Wang, Shuying Zhao, Jiaying Gao, Ya Chen, Jun Zhao, Yuxia Guo, Genyan |
author_facet | Wang, Hetong Xie, Haitao Wang, Shuying Zhao, Jiaying Gao, Ya Chen, Jun Zhao, Yuxia Guo, Genyan |
author_sort | Wang, Hetong |
collection | PubMed |
description | About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40 Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for C/C, 44.7% for C/G and 41.1% for G/G. The average tumor regression rate after 40 Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of C/C genotype was 44.6% ± 0.170, which was higher than that of genotype C/G and G/G (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F = 3.169 p = 0.045). The higher tumor regression rate in patients with C/C genotype suggested that G allele was a protective factor against radiation therapy. Using the median tumor regression rate of 34%, we divided the entire cohort into two groups, and found that the frequency distribution of PARP-1 gene rs3219073 had significant difference between these two groups (p < 0.05). These results showed that PARP-1 gene polymorphism may affect patient radiation sensitivity and predict the efficacy of radiotherapy. It therefore presents an opportunity for developing new therapeutic targets to improve radiotherapy outcome. |
format | Online Article Text |
id | pubmed-9795517 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97955172022-12-29 PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer Wang, Hetong Xie, Haitao Wang, Shuying Zhao, Jiaying Gao, Ya Chen, Jun Zhao, Yuxia Guo, Genyan Pathol Oncol Res Pathology and Oncology Archive About 70% of non-small cell lung cancer (NSCLC) patients require radiotherapy. However, due to the difference in radiation sensitivity, the treatment outcome may differ for the same pathology and choice of treatment. Poly (ADP-ribose) polymerase 1 (PARP-1) is a key gene responsible for DNA repair and is involved in base excision repair as well as repair of single strand break induced by ionizing radiation and oxidative damage. In order to investigate the relationship between PARP-1 gene polymorphism and radiation sensitivity in NSCLC, we collected 141 primary NSCLC patients undergoing three-dimensional conformal radiotherapy. For each case, the gross tumor volumes (GTV) before radiation and that after 40 Gy radiation were measured to calculate the tumor regression rate. TaqMan real-time polymerase chain reaction was performed to genotype the single-nucleotide polymorphisms (SNPs). Genotype frequencies for PARP-1 genotypes were 14.2% for C/C, 44.7% for C/G and 41.1% for G/G. The average tumor regression rate after 40 Gy radiation therapy was 35.1% ± 0.192. Tumor regression rate of mid-term RT of C/C genotype was 44.6% ± 0.170, which was higher than that of genotype C/G and G/G (32.4% ± 0.196 and 34.8% ± 0.188, respectively) with statistical significance (F = 3.169 p = 0.045). The higher tumor regression rate in patients with C/C genotype suggested that G allele was a protective factor against radiation therapy. Using the median tumor regression rate of 34%, we divided the entire cohort into two groups, and found that the frequency distribution of PARP-1 gene rs3219073 had significant difference between these two groups (p < 0.05). These results showed that PARP-1 gene polymorphism may affect patient radiation sensitivity and predict the efficacy of radiotherapy. It therefore presents an opportunity for developing new therapeutic targets to improve radiotherapy outcome. Frontiers Media S.A. 2022-12-14 /pmc/articles/PMC9795517/ /pubmed/36590386 http://dx.doi.org/10.3389/pore.2022.1610751 Text en Copyright © 2022 Wang, Xie, Wang, Zhao, Gao, Chen, Zhao and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pathology and Oncology Archive Wang, Hetong Xie, Haitao Wang, Shuying Zhao, Jiaying Gao, Ya Chen, Jun Zhao, Yuxia Guo, Genyan PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
title | PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
title_full | PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
title_fullStr | PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
title_full_unstemmed | PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
title_short | PARP-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
title_sort | parp-1 genetic polymorphism associated with radiation sensitivity of non-small cell lung cancer |
topic | Pathology and Oncology Archive |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9795517/ https://www.ncbi.nlm.nih.gov/pubmed/36590386 http://dx.doi.org/10.3389/pore.2022.1610751 |
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