北方地区汉族人核苷酸剪切修复基因mRNA的表达与头颈鳞癌发病风险的初步研究

目的:探讨我国北方汉族人核苷酸剪切修复(Nucleotide excision repair,NER)基因mRNA的表达水平与头颈鳞癌发病风险的相关性,为头颈鳞癌的诊断提供新的生物学标志物。方法:收集205例头颈鳞癌患者和176例健康对照,均为我国北方地区汉族人。通过实时定量聚合酶链反应实验检测研究对象外周血淋巴细胞中的5个核心核苷酸剪切修复基因mRNA的相对表达情况。对病例和对照之间一般特征的分布差异进行卡方检验,通过Wilcoxon秩和检验计算不同基因的mRNA表达水平的差异。采用logistic回归计算优势比(OR值)及95%置信区间(95%CI)。此外,通过ROC曲线评价NER基因模型的诊断价值。结果:病例组DDB1的mRNA表达低于对照组(P=0.075)。在logistic回归分析中,矫正年龄、性别、吸烟状况和饮酒因素后,DDB1的mRNA相对表达水平与SCCHN患病风险关系的ORs,在第二、第三和第四四分位数水平中分别为1.90(95%CI,1.02-3.54)、1.54(95%CI,0.82-2.87)和1.88(95%CI,1.00-3.52),分布与其mRNA的高表达水平相比。此外,DDB1(Ptrend=0.036)的蛋白表达水平降低与SCCHN风险增加之间也存在剂量反应关系)。ROC曲线提示DDB1表达水平与性别结合的效应模型中AUC显著改善(P=0.046)。结论:我国北方汉族DDB1的mRNA相对表达的降低与SCCHN患病风险的增加显著相关。

A Preliminary Study on the mRNA Expression of Nucleotide Excision Repair Genes in the Lymphocytes and the Risk of Head and Neck Squamous Cell Carcinoma in the Northern Chinese Population

ABSTRACT Objective: To investigate the association between mRNA expression levels of nucleotide excision repair(NER) genes and risk of the squamous cell carcinoma of head and neck (SCCHN) in northern Chinese population. Methods: 205 SCCHN patients and 176 cancer-free controls were recruited from northern part of China. The mRNA expression levels of five core NER genes were measured by quantitative real-time PCR. The Chi-square test was used to evaluate differences in demographic variables between cases and controls. Wilcoxon rank sum test were used to compare differences in the relative mRNA expression levels. The associations of NER genes mRNA expression levels with SCCHN risk were estimated by computing ORs and CIs from logistic regression analysis. To assess the improvement of SCCHN risk models, we compared the ROC curve among two risk models. Results: Compared with the controls, patients had lower expression levels of DDB1 (P=0.075). After dividing the subjects by controls'' quartiles of expression levels, we found an association between an increased risk of SCCHN and low DDB1 expression levels adjusted ORs and 95% CIs: 1.90 and 1.02-3.54, 1.54 and 0.82-2.87, 1.88 and 1.00-3.52 for the 2nd - 4th quartiles, respectively, compared with the 1st quartile; Ptrend = 0.036]. The sensitivity of the expanded model was significantly improved with the model including DDB1 expression levels and sex. Conclusion: Reduced DDB1 expression levels were associated with an increased risk of SCCHN in the northern Chinese population.