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

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.

Keywords: NF-κB pathway; cell cycle; clinical responses; nasopharyngeal carcinoma (NPC); single nucleotide polymorphism (SNP).