Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892, USA.
Carcinogenesis. 2011 Jan;32(1):69-73. doi: 10.1093/carcin/bgq204. Epub 2010 Oct 7.
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 (OR(adjusted)) 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, P(trend) = 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 (P(trend) = 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.
近三十年来，诱变挑战和 DNA 修复测定已被用于病例对照研究，以评估人类癌症风险。由于癌症诊断后才抽取血液，因此这些结果可能存在偏差，这种偏差称为“反向因果关系”，这一发现仍存在争议。因此，我们使用前瞻性采集的外周血样本建立的 Epstein-Barr 病毒转化的淋巴母细胞系，评估了与三种 DNA 修复测定相关的肺癌风险：碱性彗星试验、诱变苯并[a]芘二醇环氧化物的宿主细胞活化（HCR）测定和博来霉素致突变敏感性测定。病例（n = 117）在采血后 0.3 至 6 年内被诊断为肺癌，对照组（n = 117）按日历年份和采血时年龄、性别和吸烟史进行频数匹配，包括所有种族。实验室研究人员对病例和对照状态不知情。在非条件逻辑回归分析中，博来霉素致突变敏感性的四分位组与最低四分位组相比，肺癌的比值比（OR（调整））呈统计学显著增加[相对比，OR = 1.2，95%置信区间（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]。与之前肺癌研究报道的结果相比，博来霉素试验与肺癌风险之间的关联强度适中，但当我们仅纳入采血 1 年以上诊断的新发病例时，关联强度增强（P（趋势）= 0.02），支持该测定可能是癌症易感性的一种衡量指标。彗星和 HCR 测定与肺癌风险无关。
