The impacts of single nucleotide polymorphisms in genes of cell cycle and NF-kB pathways on the efficacy and acute toxicities of radiotherapy in patients with nasopharyngeal carcinoma.

Chengxian Guo,Lijuan Liu,Min Huang,Chunling Jiang,Lihua Huang,Yuling Huang,Yulu Liao,Jingjing Yu,Jingao Li,Guoping Yang,Xiaochang Gong

doi:10.18632/oncotarget.15835

Chengxian Guo, Lijuan Liu + Show 9 more

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https://doi.org/10.18632/oncotarget.15835

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Abstract

Radiotherapy is one of the primary choices for the treatment of nasopharyngeal carcinoma (NPC) and may result in severe radiotoxicities on normal tissues. Single nucleotide polymorphisms (SNPs) in genes of cell cycle and NF-κB pathways have been linked with the prognoses of various cancers. The aim of this study was to explore whether SNPs of genes involved in cell cycle and NF-κB pathways are associated with responses to radiotherapy in NPC patients. We selected 3 SNPs in cell cycle pathway and 5 SNPs in NF-κB pathway and genotyped them in 154 NPC patients treated with radiotherapy. Multivariate logistic regression was used to determine the association of these 8 SNPs with the responses to radiotherapy. We observed that cyclin-dependent kinase inhibitor gene CDKN2A rs3088440 was significantly related with a poorer treatment efficacy on the primary tumor and cervical lymph node after radiotherapy, and also with a decreased risk of grade 3–4 acute radiation-induced myelosuppression. In some subgroups, cyclin D1 gene CCND1 rs9344 and inhibitor of κB kinase gene IKBKB rs12676482 were related with the grade 3–4 acute radiation-induced myelosuppression, and CCND1 rs9344 was also associated with grade 3–4 acute radiation-induced oral mucositis. The current results reveal that SNPs in genes of cell cycle pathwayand NF-κB pathway have the potential to predict the clinical responses to radiotherapy for NPC patients.

Highlights

Nasopharyngeal carcinoma (NPC) is one of the common head and neck cancers originating from the epithelial lining of the nasopharynx [1]
The aim of this study was to explore whether single nucleotide polymorphism (SNP) of genes involved in cell cycle and nuclear factor-kappa B (NF-κB) pathways are associated with responses to radiotherapy in nasopharyngeal carcinoma (NPC) patients
We selected 3 SNPs in cell cycle pathway and 5 SNPs in NF-κB pathway and genotyped them in 154 NPC patients treated with radiotherapy

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is one of the common head and neck cancers originating from the epithelial lining of the nasopharynx [1]. With a notably ethnically and geographically distributed imbalance, the incidence of NPC is much higher in southern China than Western countries [2]. Radiotherapy is one of the primary choices for the treatment of NPC due to the deep-rooted histological location and relative radiosensitivity of the carcinoma [3]. Since radiation may effect on normal tissues, patients treated with radiotherapy often suffer some complications like dermatitis, oral mucositis, dysphagia and hoarseness, which severely reduce www.impactjournals.com/oncotarget the patients’ life quality and even reduce the treatment efficacy due to frequent dose adjustment and delays of radiotherapy [4, 5]. The clinical outcome and the incidence of complications are heterogeneous among patients, which can be attributed to demographic and environmental factors, and genetic factors [6]

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