Li Donghui, Wang Li-E, Chang Ping, El-Naggar Adel K, Sturgis Erich M, Wei Qingyi
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Res. 2007 Jun 15;67(12):5628-34. doi: 10.1158/0008-5472.CAN-07-0983.
In this large confirmatory study of 803 patients with squamous cell carcinoma of head and neck (SCCHN) and 839 controls frequency matched by age, sex, and ethnicity, we further examined potential predictors of benzo[a]pyrene diol epoxide (BPDE)-induced adduct levels and their associations with SCCHN risk. BPDE-DNA adduct levels were determined by the (32)P-postlabeling method in peripheral lymphocytes after in vitro challenged by BPDE. We also genotyped for GSTM1 null, GSTT1 null, GSTP1 Ile(105)Val, and GSTP1 Ala(114)Val. Potential predictors of BPDE-DNA adducts were evaluated by stratification and multivariate linear regression analyses and the association between adduct levels and SCCHN risk by multivariate logistic regression analyses. We found that mean BPDE-DNA adduct levels (the relative adduct labeling x 10(7) +/- SD) were significantly higher in cases (77.6 +/- 111.8) than in controls (57.3 +/- 98.3; P < 0.001). Using the median control value (29.22) as a cutoff, 63% of the cases were distributed above this level (adjusted odds ratio, 1.71; 95% confidence interval, 1.39-2.10). A significant dose-response relationship was observed between adduct quartiles and SCCHN risk (P(trend) < 0.001). Multivariate linear regression analysis revealed that ethnicity and smoking were significant predictors of BPDE-DNA adduct levels in controls. In conclusion, we confirmed the previously reported association between in vitro BPDE-induced DNA adduct levels and SCCHN risk, and the assay may help identify individuals at high risk of developing smoking-related cancers.
在这项针对803例头颈部鳞状细胞癌（SCCHN）患者及839例按年龄、性别和种族进行频率匹配的对照者的大型验证性研究中，我们进一步检测了苯并[a]芘二醇环氧化物（BPDE）诱导的加合物水平的潜在预测因素及其与SCCHN风险的关联。通过在体外经BPDE刺激后，采用³²P后标记法测定外周淋巴细胞中的BPDE-DNA加合物水平。我们还对谷胱甘肽S-转移酶M1（GSTM1）缺失、谷胱甘肽S-转移酶T1（GSTT1）缺失、谷胱甘肽S-转移酶P1（GSTP1）异亮氨酸（Ile）105缬氨酸（Val）及谷胱甘肽S-转移酶P1丙氨酸（Ala）114缬氨酸进行基因分型。通过分层和多变量线性回归分析评估BPDE-DNA加合物的潜在预测因素，并通过多变量逻辑回归分析评估加合物水平与SCCHN风险之间的关联。我们发现，病例组的平均BPDE-DNA加合物水平（相对加合物标记×10⁷±标准差）（77.6±111.8）显著高于对照组（57.3±98.3；P<0.001）。以对照组的中位数（29.22）作为临界值，63%的病例分布在此水平之上（校正比值比，1.71；95%置信区间，1.39 - 2.10）。在加合物四分位数与SCCHN风险之间观察到显著的剂量反应关系（P趋势<0.001）。多变量线性回归分析显示，种族和吸烟是对照组中BPDE-DNA加合物水平的显著预测因素。总之，我们证实了先前报道的体外BPDE诱导的DNA加合物水平与SCCHN风险之间的关联，并且该检测方法可能有助于识别患吸烟相关癌症风险较高的个体。
