Molecular epidemiology study on carcinogenic mechanism of Epstein-Barr-associated nasopharyngeal carcinoma and modification by environmental factors in southern China

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Epstein-Barr virus-infected nasopharyngeal carcinoma (NPC) is an important health problem in southern China. We obtained serum and biopsy specimens of nasopharyngeal tissues from NPC patients in southern China. We performed double immunofluorescent staining to examine the formation of nitrative and oxidative DNA lesions (8-nitroguanine, and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG)) in these specimens. DNA lesions were observed in cancer cells and inflammatory cells of NPC patients. Intensive immunoreactivity of iNOS was detected in the cytoplasm of cancer cells. Nuclear accumulation of EGFR and STAT3 activation by IL-6 may play the key role in iNOS expression and resultant DNA damage, leading to EBV-mediated NPC. The serum level of 8-oxodG in the NPC patients was significantly higher than that in the control. Promoter hypermethylation of Ras-related associated with diabetes (RRAD) was detected in all six NPC cell lines and most of primary NPC tissues. These findings may provide a strategy for preventing the development of NPC.