LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam

Abstract

Nasopharyngeal carcinoma (NPC) is the most common cancer among head and neck cancers in Vietnam. We aimed to identify the rate of a 30 bp deletion mutation of the LMP1-EBV gene in nasopharyngeal biopsy tissue samples, the HLA genotypes of NPC patients, and the relationship between these two targets. Patients with NPC at Can Tho Oncology Hospital from September 2014 to December 2018 were selected. A length of 30 bp of the del-LMP1-EBV gene was analyzed using a PCR technique, and the HLA genotypes in patients’ blood samples were analyzed with PCR-SSO technology. HLA-B*15 gene carriers had the highest risk of 30 bp LMP1-EBV gene deletion mutation, which was found in 51 out of 70 patients (72.9%). Carriers of the HLA-B*15 allele had a 4.6-fold increased risk of a 30 bp del-LMP1-EBV gene compared with non-carriers of this allele. The initial identification of NPC was related to the 30 bp del-LMP1-EBV gene and high frequencies of the -A*02, -B*15, -DRB1*12, -DQB1*03, and -DQA1*01 HLA alleles. Our study results suggest an association of the 30 bp del-LMP1-EBV gene and the HLA-B*15 allele with NPC susceptibility.

Large-Scale Whole-Exome Sequencing Association Study Implicates Genetic Effects on Viral Oncogenesis and Tumor Microenvironment in Nasopharyngeal Carcinoma

“…Furthermore, we observed that endothelial cells expressing SELE, particularly those with the S149R mutation, significantly render stronger migration and tumorigenesis to malignant NPC cells. This supports the crucial role of E-selectin in interacting with cancer cells and modulating metastasis across various cancers 36,51–53 . Therefore, these findings suggest that the SELE- S149R may enhance the adhesion function of E-Selectin in endothelial cells, reshaping the key TME component to favor the progression of cancer cells 53 , consequently altering individual susceptibility to NPC.…”

“…Stepwise conditional analysis localized three independently associated variants, including HLA-DQB1*03:01:01 , HLA-A: A_62_Q , and rs1050462 at HLA-B ( Tables 1, Table S1 ). Except for the two known associations at HLA-A: A_62_Q and HLA-DQB1*03:01:01 18,29 , the association of rs1050462 with NPC was a novel discovery whose signal is not attributed to previously reported HLA variants 8,10,11 (see Methods; P ≤ 3.23 × 10 -5 ; Table S3 ), according to an additional conditional analysis using an extended GD-SYSUCC cohort consisting of 1,583 cases and 3,049 controls with GWAS array data 17 .…”

“…Our study has highlighted SELE as a novel NPC-associated gene. This association is likely attributed to the rare germline mutation rs5361 in SELE , which encodes an adhesion protein E-Selectin, known for its interactions with various cells, including leukocytes and malignant epithelial cells 36,50 . A previous study has demonstrated that the deleterious S149R encoded by rs5361 enhances the functionality of E-Selectin in endothelial cells, promoting their rolling and adhesion capabilities 37 .…”

Correction: Trinh et al. LMP1-EBV Gene Deletion Mutations and HLA Genotypes of Nasopharyngeal Cancer Patients in Vietnam. Pathophysiology 2023, 30, 1–12

“…The authors would like to make the following corrections to the paper published [ 1 ] in Pathophysiology journal.…”

“…Regrettably, following publication, concerns were brought to the attention of the publisher regarding a possible overlap between the article [ 1 ] and two earlier articles [ 2 , 3 ] originating from the same authorship group and published in another language.…”