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Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy

The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway a...

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Autores principales: Senghore, Thomas, Chien, Huei-Tzu, Wang, Wen-Chang, Chen, You-Xin, Young, Chi-Kuang, Huang, Shiang-Fu, Yeh, Chih-Ching
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351919/
https://www.ncbi.nlm.nih.gov/pubmed/30609649
http://dx.doi.org/10.3390/jcm8010033
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author Senghore, Thomas
Chien, Huei-Tzu
Wang, Wen-Chang
Chen, You-Xin
Young, Chi-Kuang
Huang, Shiang-Fu
Yeh, Chih-Ching
author_facet Senghore, Thomas
Chien, Huei-Tzu
Wang, Wen-Chang
Chen, You-Xin
Young, Chi-Kuang
Huang, Shiang-Fu
Yeh, Chih-Ching
author_sort Senghore, Thomas
collection PubMed
description The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and clinical outcomes in oral squamous cell carcinoma (OSCC) patients treated with concurrent chemoradiotherapy (CCRT). Thirteen SNPs in five key NER genes were genotyped in 319 male OSCC patients using iPLEX MassARRAY. Cox proportional hazards models and Kaplan–Meier survival curves were used to estimate the risk of death or recurrence. Carriers of the XPC rs2228000 TT genotype showed a borderline significant increased risk of poor overall survival under the recessive model (hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 0.99–3.29). The CC genotypes of ERCC5 rs17655 (HR = 1.54, 95% CI = 1.03–2.29) and ERCC1 rs735482 (HR = 1.65, 95% CI = 1.06–2.58) were associated with an increased risk of worse disease-free survival under the recessive model. In addition, participants carrying both the CC genotypes of ERCC5 rs17655 and ERCC1 rs735482 exhibited an enhanced susceptibility for recurrence (HR = 2.60, 95% CI = 1.11–6.09). However, no statistically significant interaction was observed between them. Our findings reveal that the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were associated with an increased risk of recurrence in male patients with OSCC treated with CCRT. Therefore, CCRT may not be beneficial, and alternative treatments are required for such patients.
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spelling pubmed-63519192019-02-01 Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy Senghore, Thomas Chien, Huei-Tzu Wang, Wen-Chang Chen, You-Xin Young, Chi-Kuang Huang, Shiang-Fu Yeh, Chih-Ching J Clin Med Article The nucleotide excision repair (NER) pathway plays a major role in the repair of DNA damaged by exogenous agents, such as chemotherapeutic and radiotherapeutic agents. Thus, we investigated the association between key potentially functional single nucleotide polymorphisms (SNPs) in the NER pathway and clinical outcomes in oral squamous cell carcinoma (OSCC) patients treated with concurrent chemoradiotherapy (CCRT). Thirteen SNPs in five key NER genes were genotyped in 319 male OSCC patients using iPLEX MassARRAY. Cox proportional hazards models and Kaplan–Meier survival curves were used to estimate the risk of death or recurrence. Carriers of the XPC rs2228000 TT genotype showed a borderline significant increased risk of poor overall survival under the recessive model (hazard ratio (HR) = 1.81, 95% confidence interval (CI) = 0.99–3.29). The CC genotypes of ERCC5 rs17655 (HR = 1.54, 95% CI = 1.03–2.29) and ERCC1 rs735482 (HR = 1.65, 95% CI = 1.06–2.58) were associated with an increased risk of worse disease-free survival under the recessive model. In addition, participants carrying both the CC genotypes of ERCC5 rs17655 and ERCC1 rs735482 exhibited an enhanced susceptibility for recurrence (HR = 2.60, 95% CI = 1.11–6.09). However, no statistically significant interaction was observed between them. Our findings reveal that the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were associated with an increased risk of recurrence in male patients with OSCC treated with CCRT. Therefore, CCRT may not be beneficial, and alternative treatments are required for such patients. MDPI 2019-01-01 /pmc/articles/PMC6351919/ /pubmed/30609649 http://dx.doi.org/10.3390/jcm8010033 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Senghore, Thomas
Chien, Huei-Tzu
Wang, Wen-Chang
Chen, You-Xin
Young, Chi-Kuang
Huang, Shiang-Fu
Yeh, Chih-Ching
Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
title Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
title_full Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
title_fullStr Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
title_full_unstemmed Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
title_short Polymorphisms in ERCC5 rs17655 and ERCC1 rs735482 Genes Associated with the Survival of Male Patients with Postoperative Oral Squamous Cell Carcinoma Treated with Adjuvant Concurrent Chemoradiotherapy
title_sort polymorphisms in ercc5 rs17655 and ercc1 rs735482 genes associated with the survival of male patients with postoperative oral squamous cell carcinoma treated with adjuvant concurrent chemoradiotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6351919/
https://www.ncbi.nlm.nih.gov/pubmed/30609649
http://dx.doi.org/10.3390/jcm8010033
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