Wu X, Gu J, Hong W K, Lee J J, Amos C I, Jiang H, Winn R J, Fu K K, Cooper J, Spitz M R
Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, and The University of Texas School of Public Health, Houston 77030, USA.
J Natl Cancer Inst. 1998 Sep 16;90(18):1393-9. doi: 10.1093/jnci/90.18.1393.
Tobacco smoking is an established risk factor for cancers of the upper aerodigestive tract, and measurement of chromosomal aberrations, i.e., chromatid breaks, induced in lymphocytes in vitro by bleomycin has been shown to be a predictor of risk for these cancers. In a case-control study, we recruited case subjects who were previously treated with surgery and/or radiotherapy for stage I or stage II squamous cell carcinoma of the head and neck to test the hypothesis that lymphocytic chromatid breaks induced by benzo[a]pyrene diol epoxide (BPDE), a tobacco mutagen, may also be associated with risk of developing cancers of the upper aerodigestive tract.
Case subjects were matched to control subjects on the basis of age, sex, ethnicity, and smoking status. Primary lymphocytes from 67 case subjects and 81 control subjects were treated with 2 microM BPDE for 24 hours, and the frequency of induced chromatid breaks was determined. All statistical tests were two-sided.
Lymphocytes from case subjects compared with lymphocytes from control subjects showed significantly more breaks per cell induced by BPDE (mean+/-standard deviation, 0.77+/-0.38 versus 0.49+/-0.25; P<.001). Lymphocytes from 64.2% of case subjects were sensitive to BPDE (using a cutoff value of > or =0.60 break per cell). Subjects in the highest quartile of chromatid breaks had an approximately 20-fold increased risk of cancer compared with those in the lowest quartile after adjustment for age, sex, ethnicity, and smoking status. The association between BPDE sensitivity and cancer risk was higher in former smokers than in current smokers and higher in younger patients than in older patients. Subjects with sensitivity to both BPDE and bleomycin were at a 19.2-fold increased risk of cancer compared with those who were not sensitive to either agent.
Mutagen sensitivity assays may aid in identifying individuals at risk of cancer, and use of parallel assays with two mutagens may improve risk predictability.
吸烟是上消化道癌症的既定风险因素，体外博来霉素诱导淋巴细胞产生的染色体畸变（即染色单体断裂）的测量已被证明是这些癌症风险的预测指标。在一项病例对照研究中，我们招募了曾接受手术和/或放疗治疗的I期或II期头颈部鳞状细胞癌患者作为病例组，以检验烟草诱变剂苯并[a]芘二醇环氧化物（BPDE）诱导的淋巴细胞染色单体断裂也可能与上消化道癌症发生风险相关这一假设。
根据年龄、性别、种族和吸烟状况将病例组与对照组进行匹配。对67例病例组和81例对照组的原代淋巴细胞用2微摩尔BPDE处理24小时，并确定诱导的染色单体断裂频率。所有统计检验均为双侧检验。
与对照组淋巴细胞相比，病例组淋巴细胞经BPDE诱导后每个细胞的断裂数显著更多（均值±标准差，0.77±0.38对0.49±0.25；P<0.001）。64.2%的病例组淋巴细胞对BPDE敏感（采用每个细胞≥0.60个断裂的临界值）。在调整年龄、性别、种族和吸烟状况后，染色单体断裂处于最高四分位数的受试者患癌风险比处于最低四分位数的受试者增加约20倍。BPDE敏感性与癌症风险之间的关联在既往吸烟者中高于当前吸烟者，在年轻患者中高于老年患者。对BPDE和博来霉素均敏感的受试者患癌风险比两种药物均不敏感的受试者增加19.2倍。
诱变剂敏感性检测可能有助于识别癌症风险个体，使用两种诱变剂的平行检测可能会提高风险预测能力。
