Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
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对前列腺癌、肺癌、结直肠癌和卵巢癌 (PLCO) 癌症筛查试验中肺癌风险的 DNA 损伤和修复标志物进行前瞻性分析。
DOI：
10.1093/carcin/bgq204
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发表时间：
2011
期刊：
影响因子：
4.7
通讯作者：
Caporaso,NeilE
中科院分区：
文献类型：
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作者：
Sigurdson,AliceJ;Jones,IreneM;Wei,Qingyi;Wu,Xifeng;Spitz,MargaretR;Stram,DouglasA;Gross,MyronD;Huang,Wen-Yi;Wang,Li-E;Gu,Jian;Thomas,CynthiaB;Reding,DouglasJ;Hayes,RichardB;Caporaso,NeilE
诱变剂挑战和DNA修复试验已用于病例对照研究近30年，以评估人类癌症风险。这一发现仍然引起了争议，因为血液是在癌症诊断后提取的，所以结果可能是有偏见的，一种被称为“反向因果关系”的类型。因此，我们使用从前瞻性收集的外周血液样本建立的Epstein-Barr病毒转化的淋巴母细胞系来评估与三种DNA修复试验有关的肺癌风险：碱性彗星试验、用苯并[a]芘二醇环氧化物诱变的宿主细胞再激活(HCR)试验和博莱霉素诱变剂敏感性试验。病例(n=117)在采血后0.3~6年被诊断为肺癌，对照组(n=117)在采血时的历年和年龄、性别和吸烟史上进行频率匹配，包括所有种族。实验室调查人员不知道病例和对照状态。在非条件Logistic回归分析中，以每细胞染色单体断裂的四分位数表示的博莱霉素诱变剂敏感性显著增加[相对于最低四分位，OR=1.2，95%可信区间(CI)：0.5~2.5；OR=1.4，95%CI：0.7~3.1；OR=2.1，95%CI：1.0~4.4，P趋势=0.04]。与以前的肺癌研究报告相比，博莱霉素检测与肺癌风险之间的关联程度并不大，但当我们只包括采集血液后一年以上确诊的偶发病例时，这种关联得到了加强(P趋势=0.02)，支持了该检测可能是癌症易感性的衡量标准的观点。彗星和HCR检测与肺癌风险无关。
Mutagen challenge and DNA repair assays have been used in case–control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called ‘reverse causation’. We therefore used Epstein–Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n= 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n= 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (ORadjusted) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5–2.5; OR = 1.4, 95% CI: 0.7–3.1; OR = 2.1, 95% CI: 1.0–4.4, respectively,Ptrend= 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (Ptrend= 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.