致突变剂敏感性与头颈肿瘤患者放化疗后第二原发肿瘤发生风险的研究  

Study of Mutagen Sensitivity and the Risk of Developing Secondary Primary Tumors after Radiotherapy and/or Chemotherapy in Patients with Head and Neck Cancers

作　　者：秦俭[1] 王仁生[2] 莫耀喜 滕家安[4] 杨慧华[5] 李婷婷[6] 

机构地区：[1]广西壮族自治区人民医院临床肿瘤中心放疗病区,广西南宁530021 [2]广西医科大学第一附属医院放疗科 [3]广西壮族自治区人民医院生殖中心实验室 [4]广西壮族自治区人民医院内分泌代谢干部病区 [5]北海市人民医院血液科 [6]柳州市工人医院妇产科

出　　处：《中国辐射卫生》2014年第4期299-302,共4页Chinese Journal of Radiological Health

基　　金：广西自然科学基金青年基金项目(2010GXNSFB013081007)

摘　　要：目的探讨基因稳定性与头颈肿瘤患者放化疗后发生第二原发肿瘤（secondary primary tumor,SPT）的关系。方法SPT组和无SPT组入组病例分别为67、47例,正常对照组40例。以博莱霉素作为致突变剂,分析既往有头颈肿瘤放疗±化疗史、发生和未发生SPT者,分析外周血淋巴细胞平均染色单体断裂数。结果从初诊头颈肿瘤的年龄开始,SPT组至发生SPT的时间、无SPT组至最后随访时间分别为16.73±6.31（95%CI,15.19~18.27）和18.51±8.51（95%CI,16.01~21.01）年（F=1.643,P=0.203）。发生SPT的部位主要是头颈部,病理类型以鳞癌居多。SPT组、无SPT组和对照组外周血淋巴细胞平均染色单体断裂数分别为0.88±0.29（95%CI,0.81~0.95）、0.56±0.19（95%CI,0.50~0.61）和0.52±0.18（95%CI,0.46~0.58）个,差异有统计学意义（F=6.519,P=0.002）。以≥0.5个断裂数/细胞作为博莱霉素敏感性高低的分界点,3组对博莱霉素敏感的百分比分别为85.07%、65.96%、52.50%,差异有统计学意义（χ2=13.611,P=0.000）。将SPT组设置为病例组,余为对照组,外周血淋巴细胞平均染色单体断裂数的ROC曲线下面积为0.829,标准误是0.037（P=0.000）,该值为0.69时特异性和敏感性均较高。结论头颈肿瘤患者潜在的基因不稳定性与SPT密切相关;发生SPT的潜伏期较长,超过10年;外周血淋巴细胞平均染色单体断裂数判断该患者人群发生SPT的风险有价值,≥0.69可以作为高危SPT的最佳阈值,但需要进一步验证。Objective To discuss the relationship between genetic stability and secondary prinmry tumor （SPT） ＇after rahotherapy and/or chemotherapy in patients with head - and - neck cancers. Methods Compared bleomycin - induced chronratid breaks in peripheral blood lymphocyte cultures （as an indicator of latent genetic instability） between 67 cases （patients with SPT） and 47 controis （ head - and - neck cancer patients without SPT）. Results The time from the age of new diagnosis of head - and - neck cancer to SPT in SPT group was 16. 73± 6.31 （95% CI, 15.19 - 18.27） years, and to the last follow - up time in no - SPT group wag 18.51 ± 8.51 （95% CI, 16. 01 -21.01 ） years, respectively. The major tumor site and pathologic type eft SPT was head -and -neck squamous carcinoma. The mean number of chromatid breaks per cell was significantly higher in SPT group 0.88 ±0. 29（95% CI, 0.81-0.95） than in no -SPT 0.56 ±0. 19（95% CI, 0.50 -0.61 ） and the controls 0.52 ±0. 18（95%CI, 0.46 -0.58） （F =6. 519, P =0. 002）. Low and high bleomycin sensitivity was determined by using 0. 5 breaka/cell as a cutoff point. The high sensitivity ratio in SPY, no - SPT and control group were 85.07%, 65.96% and 52.50%, respectively （x^2 = 13.611 ,P =0. 000）. SPT as cases and others as controls, the area under ROC curve of the mean number of chromatid breaks per cell was 0. 829, the standard emir was 0.037 （P = 0. 000） . The best cutoff point was 0.69. Conclusion The latent genetic instability is closely related with SPT in patients with head and neck cancers after radiotherapy and/or chemotherapy. The incubation period of SPT is as hmg as more than a decade. The mean number of chromatid breaks per cell is worth to estimate high risk of developing SPT in these patients. The optimal threshold value is 0.69, further verifications need be proceeding.

关 键 词：头颈肿瘤 第二原发肿瘤 博莱霉素 基因稳定性 

分 类 号：R815.6[医药卫生—放射医学]