Objective: Nasopharyngeal carcinoma (NPC) is a severe malignant disease. Despite its low frequency, NPC is very common in North African population. Radiotherapy is the standard therapeutic treatment of NPC. However, radioresistance hampers the success of treatment. At the molecular scale, radioresistance is due to genetic variations involved in DNA repair pathways in NPC patients. Several studies reported that single nucleotide polymorphisms (SNPs) in excision repair cross complementing group 1 (ERCC1) could be associated with radioresistance. In this optic, the present study aimed to evaluate the association between DNA repair gene polymorphisms ERCC1 C8092A and ERCC1 C118T and radiotherapy response of patients with NPC. Methods: A total of 95 patients with confirmed NPC were recruited at the Mohammed VI Center for Cancer Treatment, Casablanca -Morocco between 2016 and 2018. Two single nucleotide polymorphisms in ERCC1 gene were genotyped. Multiple analysis software was used to assess the correlation between these SNPs and radio-therapeutic response. Results: Sequencing of ERCC1 C8092A polymorphism revealed that CC and CA genotypes were found in 51.6% and 45.3% of cases, respectively, whereas the homozygote AA genotype was reported in only 3.1% of cases. For ERCC1 C118T polymorphism, the heterozygote CT genotype was identified in 49.5% of cases. Homozygotes genotypes CC and TT were detected in 17.9% and 32.6% respectively of NPC cases. Of note, no significant association was found between the ERCC1 C8092A polymorphism and response to radiation therapy (p=0.81). Similarly, there was no significant association between the response to radiotherapy and allelic distribution (p=0.56). Likewise, no correlation was observed neither with genotypes (p=0.07) nor with alleles (p=0.09) of ERCC1 C118T polymorphism and response to radiation therapy. Conclusion: Our results clearly showed that ERCC1 C8092A and ERCC1 C118T polymorphisms were not associated with response to radiotherapy in Moroccan NPC patients. Large studies are warranted to confirm the role of these SNPs in therapeutic response of NPC patients.

Nasopharyngeal cancer [NPC] is one of the most common head and neck cancers. NPC differs significantly from other cancers in its etiology, epidemiology, clinical behavior, and treatment. Being highly radiosensitive, the standard treatment for NPC is radiotherapy. However, radioresistance hampers the success of treatment and may cause local recurrence and distant metastases in NPC patients. In this review, we discuss the updated protocols for NPC diagnosis and treatment based on recent literature with an emphasis on the mechanisms of radioresistance at the molecular level with a special focus on genetic and epigenetic events, affecting genes involved in xenobiotic detoxification and DNA repair. We also highlight the importance of some cellular and Epstein Barr viral miRNAs targeting specific DNA repair factors and consequently promoting NPC radioresistance. These molecular markers may serve as promising tools for diagnosis, prognosis, and radioresistance prediction to guide theranostics of patients with NPC in the future.

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