# Investigation of genetic and lifestyle risk factors associated with Epstein-Barr virus reactivation in the Thai population

## TL;DR

This study explores genetic and lifestyle factors linked to Epstein-Barr virus reactivation in the Thai population, identifying age, habits, and genetic markers like TNF-α mutations as key contributors.

## Contribution

The study provides novel insights into EBV reactivation risk factors specific to the Thai population, including age-specific trends and genetic associations.

## Key findings

- EBV reactivation was detected in 36% of samples using the EBNA-1 gene and 52% using LMP-1 gene.
- The TNF-α mutation rs1799964 was more common in EBV-positive individuals, particularly in those with mouth ulcers.
- Lifestyle factors like alcohol consumption, smoking, and age (21-30 years) were significantly associated with EBV reactivation.

## Abstract

Current data on the genetic and lifestyle factors associated with Epstein-Barr virus (EBV) reactivation in the oral cavity are limited for the Thai population. Furthermore, comprehensive data linking EBV reactivation to head and neck cancers in Thailand remains scarce. The present study aimed to detect EBV reactivation using quantitative PCR in normal oral buccal cells and to examine the associated risk factors. A total of 982 oral buccal cell samples collected across Thailand were analyzed. EBV was detected in 36% (350/974) of samples when targeting the Epstein-Barr nuclear antigen-1 gene, 52% (458/885) of samples when targeting latent membrane protein-1 (LMP-1) and 20% (196/981) of samples when both genes were investigated. The highest prevalence of LMP-1 and dual gene positivity was observed in individuals aged 11-20 years. Several SNPs in the TNF-α promoter region, including rs1452146766, rs1799964, rs1554283139, rs924800313, rs1799724 and rs1771099055, were more frequently observed in EBV-positive samples than in EBV-negative samples. Notably, the TNF-α mutation rs1799964 (-1031 TC and CC) was present in 17.3% vs. 9.3% of EBV-positive cases, respectively. Multivariate analysis identified sex, smoking, alcohol consumption, soft drink intake, age of 21-30 years and having four children as significant factors associated with EBV reactivation. In the 21-30-year-old age group, LMP-1 positivity was elevated, and higher rates of alcohol use, sexual activity and oral ulcers were observed. Furthermore, in individuals with mouth ulcers, the TNF-α mutation (TC; n=81) was more common than wild-type TNF-α (CC; n=16).