The Advances of Genetic Susceptibility to Nasopharyngeal Carcinoma

WANG Tongmin¹, JIA Wenhui², JIA Weihua^1,2*

（¹State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510060, China; ²School of Public Health, Sun Yat-sen University, Guangzhou 510080, China)

Abstract:

NPC (nasopharyngeal carcinoma) is a malignancy originating from the epithelial cells of nasopharyngeal mucosa and is closely associated with EBV (Epstein-Barr virus) infection. It is predominantly prevalent in regions such as South China and Southeast Asia. Numerous studies have shown that genetic factor plays an important role in NPC development. Candidate gene studies and GWAS (genome-wide association studies) have identified many common variants associated with NPC risk, while recent advancements in high-throughput sequencing have facilitated the identification of rare variants involved in NPC carcinogenesis. Additionally, integration of GWAS data and other omics data such as epigenomics and transcriptomics has accelerated the discovery offunctional variants, expanding the spectrum of susceptibility genes for NPC. Moreover, important findings have also emerged regarding the interactions between susceptibility genes and EBV and its role in NPC development. This article summarizes the common and rare variants of the NPC susceptibility genes by their biological functions, focusing on immune-related genes in the HLA (human leukocyte antigen) region and non-HLA regions, and other genes involved in DNA repair pathways and tumorigenesis-related pathways, thereby presenting a comprehensive molecular landscape of genetic susceptibility to NPC and suggesting future research direction such as risk prediction, genetic consultation, and discovery of novel therapeutic target.

CSTR: 32200.14.cjcb.2025.03.0001