Hsu Wan-Lun, Chen Jen-Yang, Chien Yin-Chu, Liu Mei-Ying, You San-Lin, Hsu Mow-Ming, Yang Czau-Siung, Chen Chien-Jen
Genomics Research Center, Academia Sinica, Taipei 115, Taiwan.
Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1218-26. doi: 10.1158/1055-9965.EPI-08-1175. Epub 2009 Mar 31.
This study aimed to assess independent effects of EBV and cigarette smoking on nasopharyngeal carcinoma, which have never been assessed in long-term follow-up studies. A cohort of 9,622 men was enrolled from 1984 to 1986. Blood samples collected at study entry were tested for antibodies against EBV antigens (anti-EBV) viral capsid antigen immunoglobulin A and DNase. The cigarette smoking habit was inquired through questionnaire interview. Newly developed nasopharyngeal carcinoma cases were ascertained through computerized linkage with national cancer registry profile. Cox's proportional hazard regression analysis was used to estimate multivariate-adjusted hazard ratio with its 95% confidence interval (95% CI). During the follow-up of 173,706 person-years, 32 pathologically confirmed nasopharyngeal carcinoma cases were identified >1 year after recruitment. Increasing serum levels of anti-EBV viral capsid antigen immunoglobulin A and DNase were significantly associated with nasopharyngeal carcinoma risk in a dose-response relationship. The multivariate-adjusted hazard ratio (95% CI) of developing nasopharyngeal carcinoma for low and high antibody levels compared with seronegatives was 9.5 (2.2-40.1) and 21.4 (2.8-161.7), respectively, for anti-EBV viral capsid antigen immunoglobulin A (P < 0.001 for trend), and 1.6 (0.5-4.6) and 16.0 (5.4-47.1), respectively, for anti-EBV DNase (P < 0.001 for trend). The shorter the time interval between study entry and nasopharyngeal carcinoma diagnosis, the higher was the proportion of anti-EBV viral capsid antigen immunoglobulin A among nasopharyngeal carcinoma patients. The multivariate-adjusted hazard ratio (95% CI) was 3.0 (1.3-7.2) for > or =30 pack-years of cumulative cigarette smoking compared with <30 pack-years as the reference. The longer and heavier the cigarette smoking habit, the higher was the nasopharyngeal carcinoma risk. Anti-EBV viral capsid antigen immunoglobulin A, anti-EBV DNase, and long-term heavy cigarette smoking are independent nasopharyngeal carcinoma risk predictors.
本研究旨在评估EB病毒（EBV）和吸烟对鼻咽癌的独立影响，长期随访研究中从未对此进行过评估。1984年至1986年招募了9622名男性队列。在研究开始时采集的血样检测了针对EBV抗原（抗EBV）的病毒衣壳抗原免疫球蛋白A和脱氧核糖核酸酶的抗体。通过问卷调查询问吸烟习惯。通过与国家癌症登记档案的计算机链接确定新发生的鼻咽癌病例。采用Cox比例风险回归分析来估计多变量调整后的风险比及其95%置信区间（95%CI）。在173706人年的随访期间，招募后1年以上确定了32例经病理证实的鼻咽癌病例。抗EBV病毒衣壳抗原免疫球蛋白A和脱氧核糖核酸酶血清水平升高与鼻咽癌风险呈显著剂量反应关系。与血清阴性相比，抗EBV病毒衣壳抗原免疫球蛋白A低抗体水平和高抗体水平发生鼻咽癌的多变量调整风险比（95%CI）分别为9.5（2.2 - 40.1）和21.4（2.8 - 161.7）（趋势P < 0.001），抗EBV脱氧核糖核酸酶分别为1.6（0.5 - 4.6）和16.0（5.4 - 47.1）（趋势P < 0.001）。从研究开始到鼻咽癌诊断的时间间隔越短，鼻咽癌患者中抗EBV病毒衣壳抗原免疫球蛋白A的比例越高。与<30包年作为参考相比，累积吸烟≥30包年的多变量调整风险比（95%CI）为3.0（1.3 - 7.2）。吸烟习惯时间越长、量越大，鼻咽癌风险越高。抗EBV病毒衣壳抗原免疫球蛋白A、抗EBV脱氧核糖核酸酶和长期大量吸烟是鼻咽癌的独立风险预测因素。
