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

Thomas Senghore, Huei-Tzu Chien, Wen-Chang Wang, You-Xin Chen, Chi-Kuang Young, Shiang-Fu Huang, Chih-Ching Yeh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)33
JournalJournal of Clinical Medicine
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 1 2019

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Adjuvant Chemoradiotherapy
Chemoradiotherapy
DNA Repair
Squamous Cell Carcinoma
Genotype
Confidence Intervals
Survival
Proportional Hazards Models
Recurrence
Genes
Single Nucleotide Polymorphism
Critical Pathways
Disease-Free Survival

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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. / Senghore, Thomas; Chien, Huei-Tzu; Wang, Wen-Chang; Chen, You-Xin; Young, Chi-Kuang; Huang, Shiang-Fu; Yeh, Chih-Ching.

In: Journal of Clinical Medicine, Vol. 8, No. 1, 01.01.2019, p. 33.

Research output: Contribution to journalArticle

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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",
abstract = "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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AU - Chien, Huei-Tzu

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AU - Young, Chi-Kuang

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AB - 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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JO - Journal of Clinical Medicine

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