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

doi:10.3390/jcm8010033

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.

Highlights

Oral squamous cell carcinoma (OSCC) is the leading cause of cancer morbidity and mortality, especially among men in Taiwan [1]
Most participants were under 50 years (51.41%) old, of Taiwanese descent, had normal body mass index (BMI) (49.22%), had smoked cigarettes, drank alcohol (69.28%), and chewed betel nut (86.21%)
Our findings suggest that the XPC rs2228000 TT genotype was marginally significantly associated with increased risk of death, whereas the ERCC5 rs17655 CC and ERCC1 rs735482 CC genotypes were significantly associated with the increased risk of relapse

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the leading cause of cancer morbidity and mortality, especially among men in Taiwan [1]. While relapse of OSCC remains a major clinical challenge, the incidence of relapse among patients varies, even for those with a similar stage of disease at diagnosis or those who undergo the same treatment [3]. This implies that other factors, such as genetic variations, may play an important role in disease prognosis. Most patients with OSCC are diagnosed at an advanced stage of the disease [4] For these patients, the treatment options are limited to mainly systemic therapy, often as concurrent chemoradiotherapy (CCRT) with platinum-based DNA damaging agents as either primary treatment or adjuvant postoperative therapy [5,6,7]. Genetic variations in DNA repair genes affect susceptibility to the efficacy and survival outcome of a certain treatment [11,12]

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Discussion

Conclusion