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 investigate the relationship between gene stability and secondary primary tumor (SPT) after radiotherapy and chemotherapy in patients with head and neck cancer. Methods The cases of SPT group and no SPT group were 67,47 cases and 40 cases of normal control group respectively. Bleomycin was used as a mutagen to analyze the history of radiotherapy-chemotherapy of head and neck tumors, with or without SPT, and to analyze the mean number of chromatid breaks in peripheral blood lymphocytes. Results From the age of newly diagnosed head and neck cancer, the time from the SPT group to the occurrence of SPT and the time from the no SPT group to the last follow-up were 16.73 ± 6.31 (95% CI, 15.19-18.27) and 18.51 ± 8.51 (95% CI, 16.01-21.01 ) Years (F = 1.643, P = 0.203). The site of occurrence of SPT is mainly head and neck, the majority of squamous cell carcinoma pathological type. The number of cleaved chondrocytes in SPT group, SPT group and control group were 0.88 ± 0.29 (95% CI, 0.81-0.95), 0.56 ± 0.19 (95% CI, 0.50-0.61) and 0.52 ± 0.18 (95% CI, 0.46 ~ 0.58), the difference was statistically significant (F = 6.519, P = 0.002). The percentage of bleomycin sensitive to bleomycin was 85.07%, 65.96% and 52.50%, respectively (χ2 = 13.611), with ≥ 0.5 breakage / cell as the cut-off point of bleomycin sensitivity , P = 0.000). The SPT group was set as the case group and the remainder was the control group. The area under the ROC curve of mean number of chromatid cleavage in peripheral blood lymphocytes was 0.829, the standard error was 0.037 (P = 0.000), the specificity and sensitivity was 0.69 Sex is higher. Conclusion The potential genomic instability of head and neck cancer patients is closely related to SPT. The incubation period of SPT is longer than 10 years. The average number of chromatid of peripheral blood lymphocytes is of great value to determine the risk of SPT in this population. As the best threshold for high-risk SPT, but needs further verification.