鼻咽癌與FAS、FASL、NF-κB 和 TRAF3基因多形性之流行病學研究

Abstract

Background: Epstein-Barr virus (EBV) infection is an important risk factor for nasopharyngeal carcinoma (NPC). EBV causes the immortalization and transformation of infected cells. Tumor necrosis factor receptor-associated factor 3 (TRAF3) is required for EBV recognition and initiation of type I interferon production. It is also required for activation of B lymphocytes by EBV latent membrane protein 1 (LMP1). FAS (CD95, APO-1), FAS ligand (FASL) and nuclear factor-kappa B (NF-κB) also play important roles in the apoptosis. This case-control study aimed to examine the associations between NPC and polymorphisms of these genes. Methods: A total of 317 cases affected with histologically confirmed NPC and 268 healthy community controls matched with cases on gender, age and residence were enrolled. Blood samples were collected for the examination of IgA antibodies against EBV-specific viral capsid antigen (anti-EBV VCA IgA) and Epstein-Barr nuclear antigen 1 (anti-EBNA 1 IgA) and IgG antibodies against DNA binding protein (anti-EBV DBP IgG) and DNase (anti-EBV DNase IgG). The real-time PCR assay was used for genotyping of TRAF3 (codon 600), FAS (-1377 and –670), FASL (-844) and NF-κB (-94). Logistic regression analysis was used to estimate multivariate-adjusted odds ratio (ORadj) with its 95% confidence interval (CI) for each genotype after adjustment for age, gender, educational level, and ethnicity. Results: Genetic polymorphisms of FAS (-1377), FAS (-670), FASL (-844) and NF-kB (-94) were not significantly associated with the risk of NPC. The haplotype of FAS (-1377 and -670) was not significantly associated with NPC risk either. Individuals with the TRAF3 (codon 600) AA or AG genotype had an increased NPC risk compared with GG genotype as the referent group (ORadj, 1.85; 95% CI, 1.12-3.04). In NPC cases, family NPC history was not associated with TRAF3 (codon 600) genotype. The seropositivity of various antibodies against EBV was not significantly associated with TRAF3 (codon 600) genotype in either NPC cases or controls. TRAF3 (codon 600) genotype was associated with an increased risk of NPC in those who were seropositive on anti-EBV VCA IgA, anti-EBV DBP IgG, and anti-EBV DNase IgG. Highest NPC risk was observed for those who were anti-EBV-seropositive with AA/AG genotype of TRAF3 (codon 600). Conclusions: There is a significant association with NPC for TRAF3 genotype, but not for FAS, FASL and NF-κB genotypes. TRAF3 (codon 600) AA/AG genotype was associated with an increased risk of NPC compared with GG genotype, especially in those who were seropositive on antibodies against EBV proteins expressed in lytic infection.