Fluctuations of epstein-barr virus serological antibodies and risk for nasopharyngeal carcinoma: a prospective screening study with a 20-year follow-up.

BACKGROUND: The impact of variation of Epstein-Barr virus (EBV) antibody titers before the development of nasopharyngeal carcinoma (NPC) is still unclear. We analyzed the fluctuations of antibodies against EBV before histopathological diagnosis to assess the risk of NPC and aimed to provide a reliable basis for screening in high risk populations. METHODS: This study was based on a population-based screening program in Sihui County in Guangdong Province of China. A total of 18,986 subjects were recruited in 1987 and 1992, respectively. Baseline and repeated serological tests were performed for IgA antibodies against EBV capsid antigen (VCA/IgA) and early antigen (EA/IgA). Follow-up until the end of 2007 was accomplished through linkage with population and health registers. Cox proportional hazards regression model was used to estimate the relative risk of NPC in association with EBV antibodies. Time-dependent receiver operating characteristic curve (ROC) analysis was used to further evaluate the predictive ability. RESULTS: A total of 125 NPCs occurred during an average of 16.9 years of follow-up. Using baseline information alone or together with repeated measurements, serological levels of VCA/IgA and EA/IgA were significantly associated with increased risks for NPC, with a striking dose-response relationship and most prominent during the first 5 years of follow-up. Considering the fluctuant types of serological titers observed during the first three tests, relative risk was highest among participants with ascending titers of EBV VCA/IgA antibodies with an adjusted hazard ratio (HR) of 21.3 (95% confidence interval [CI] 7.1 to 64.1), and lowest for those with decreasing titers (HR = 1.5, 95% CI 0.2 to 11.4), during the first 5 years of follow-up. Time-dependent ROC analysis showed that VCA/IgA had better predictive performance for NPC incidence than EA/IgA. CONCLUSION: Our study documents that elevated EBV antibodies, particularly with ascending titers, are strongly associated with an increased risk for NPC.

[Long-term efficacy of radiotherapy on children with nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Nasopharyngeal carcinoma (NPC) in children is a particular type of NPC with poor prognosis. This study was to analyze long-term treatment efficacy, and relevant factors influencing prognosis of NPC in children. METHODS: From Jan. 1975 to Dec. 1995, 47 children,7-14 years old, with NPC diagnosed by pathology received radiotherapy in our hospital. Radiation doses were 52-74 Gy/6-13 weeks [(64.68+/-5.68) Gy] in nasopharynx, and 46-73 Gy/5-13 weeks [(57.77+/-5.86) Gy] in neck; 21 received 1-3 cycles of chemotherapy (cisplatin, bleomycin, 5-fluoroucil, vincristine, and cyclophosphamide) before radiotherapy. Survival rate was calculated by Kaplan-Meier method, and analyzed by log-rank test with SPSS 10.0 software. RESULTS: The 1, 3, 5-year survival rates of 47 patients were 72.3%, 53.2%, and 40.4%, respectively. Clinical stage (P=0.046), mode of biopsy (P=0.024), radiation dose in nasopharynx (P=0.049), and short-term efficacy (P=0.005) correlated with prognosis of these patients. The average height of 15 male children with NPC who survived for more than 5 years was (161.5+/-1.23) cm. Among 3 female children with NPC who survived for more than 5 years, 2 had menstruation disturbance. CONCLUSIONS: Clinical stage, mode of biopsy, radiation dose in nasopharynx, short-term efficacy may influence prognosis of NPC in children. Radiation-induced long-term sequelae of NPC in children should not be overlooked.

Genome-wide scan for familial nasopharyngeal carcinoma reveals evidence of linkage to chromosome 4.

Nasopharyngeal carcinoma (NPC) occurs with high frequency in Asian populations, especially among people of Cantonese ancestry. In areas with high incidence, NPC clusters in families, which suggests that both geography and genetics may influence disease risk. Although the HLA-Bw46 locus is associated with increased risk of NPC, no predisposing genes have been identified so far. Here we report the results of a genome-wide search carried out in families at high risk of NPC from Guangdong Province, China. Parametric analyses provide evidence of linkage to the D4S405 marker on chromosome 4 with a logarithm of odds for linkage (lod) score of 3.06 and a heterogeneity-adjusted lod (hlod) score of 3.21. Fine mapping with additional markers flanking D4S405 resulted in a lod score of 3.54 and hlod score of 3.67 for the region 4p15.1-q12. Multipoint nonparametric linkage analysis gives lod scores of 3.54 at D4S405 (P = 5.4 x 10(-5)) and 4.2 at D4S3002 (P = 1.1 x 10(-5)), which is positioned 4.5 cM away from D4S405. When Epstein Barr virus antibody titer was included as a covariate, the lod scores reached 4.70 (P = 2.0 x 10(-5)) and 5.36 (P = 4.36 x 10(-6)) for D4S405 and D4S3002, respectively. Our findings provide evidence of a major susceptibility locus for NPC on chromosome 4 in a subset of families.