Studies on Etiological Factors of Nasopharyngeal Carcinoma

Abstract

A case-control study of nasopharyngeal carcinoma (NPC) was performed in Guangzhou, southern China in 1987 to 1989. We investigated 205 cases and an equal number of matched controls. Epstein-Barr virus (EBV) infection with positive IgA against viral capsid antigen (VCA-IgA) was shown to be the most important predictor in NPC. Consumption of salted fish was also strongly associated with NPC but not to the same extent as EBV. In order to investigate the possible carcinogenic effect of salted fish, Sprague-Dawley rats were given a diet containing salted fish for 2 years. Three rats with nasal and 3 with nasopharyngeal tumors were found in the experimental groups of 122 rats but none in the control group. Nitrosodimethylamine (NDMA) was found in kidney and liver but not in urine in the rats fed with salted fish. In a non-tumorigenic human keratinocyte line, RHEK-1, transfection of EBV latent membrane protein (EBV-LMP, originated from NPC cell line) induced alterations of morphology and immunophenotype. The LMP expressing sublines showed higher proliferative capacity and lower differentiation in vitro and some of the sublines produced tumors in SCID mice. When cultured in media containing salted fish extract in vitro parental RHEK-1 cells died after 12 weeks. In contrast, LMP expressing sublines survived indicating that exposure to some chemical compounds in salted fish and expression of EBV-gene may be of importance for the transformation of epithelial cells and thus for the pathogenesis of NPC.

Key Words:

• NPC
• EBV
• salted fish
• LMP
• nitrosamine