Epstein-Barr virus (
EBV) nuclear antigen 1 (EBNA1) is the only
viral protein consistently expressed in all EBV-associated
malignancies, and play a critical role in the onset, progression, and/or maintenance of these
tumors. Based on the signature changes at
amino acid residue 487, EBNA1 is classified into five distinct subtypes: P-ala, P-thr,
V-leu, V-val and V-pro. In the present study, the sequence variations of EBNA1 in EBV-associated gastric
carcinoma (EBVaGC) and throat washing (TW) samples of healthy EBV carriers in Guangzhou, southern China, where
nasopharyngeal carcinoma (NPC) is endemic, were analyzed by PCR and
DNA sequencing. V-val subtype was the most predominant (53.6%, 15/28) in EBVaGC, followed by P-ala (42.9%, 12/28) and
V-leu (32.1%, 9/28) subtypes. In TWs of healthy EBV carriers, V-val subtype was also predominant (85.7%, 18/21). The sequence variations of EBNA1 in EBVaGC were similar to those in TW of healthy EBV carriers (p>0.05), suggesting that the EBV strains in EBVaGC might originate from the viral strains prevalent within the background population. The predominance of V-val subtype in EBVaGC in Guangzhou was similar to that in EBVaGC in northern China and Japan, but was different from that in EBVaGC in America, suggesting that the variations of EBNA1 in EBVaGC represent geographic-associated polymorphisms rather than
tumor-specific mutations. In addition, the EBNA1 variations in EBVaGC in gastric remnant
carcinoma were also determined.
V-leu subtype was detected in all 4 (100%) cases, although 2 cases occurred as
mixed infection with P-ala subtype. This is different from the predominant V-val subtype in EBVaGC in conventional gastric
carcinoma, suggesting that
V-leu might be a subtype that adapts particularly well to the microenvironment within the gastric stump and enters the remnant gastric mucosa epithelia easily. This, to our best knowledge, is the first investigation of EBNA1 polymorphisms in EBVaGC from endemic area of NPC.