Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L'Hospitalet de Llobregat, Barcelona 08908, Spain.
Cancer Risk Factor Branch, ISPO-Cancer Prevention and Research Institute, Florence 50131, Italy.
Carcinogenesis. 2014 Sep;35(9):2047-54. doi: 10.1093/carcin/bgu098. Epub 2014 Apr 29.
In this case-cohort study, we examined the association between bulky DNA adducts and the risk of lung cancer within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort with an average 7-year follow-up, including 98 cases of primary lung cancer and 296 subjects randomly selected from the cohort. Aromatic adducts were measured using (32)P-postlabeling in leukocyte DNA from blood samples collected at enrollment. The association between DNA adducts and the risk of lung cancer was estimated using a Cox proportional hazards model with a modified partial likelihood. There was an overall significant increased risk for developing lung cancer when DNA adduct concentrations were doubled, with relative risk (RR) adjusting for all relevant confounders of 1.36 with 95% confidence interval (CI) 1.18-157. There was a significant increased risk for developing lung cancer when DNA adduct concentrations were doubled for current smokers and among subjects exposed to PAH at work; there was also a slightly higher increase among males than females. However, no statistically significant differences were observed for the effect of adduct levels across smoking status, sex or occupational exposure to PAH. A meta-analysis combined four prospective studies, including this study, resulting in a significant association among current smokers, with an overall estimate of 34% increase in the risk of lung cancer when doubling the level of aromatic DNA adducts in leukocytes.
在这项病例-队列研究中，我们研究了在欧洲癌症前瞻性调查和营养研究（EPIC）西班牙队列中，平均 7 年随访期间，大块 DNA 加合物与肺癌风险之间的关联，该队列包括 98 例原发性肺癌病例和 296 名随机选自该队列的受试者。在入组时采集的血液样本中，使用（32）P-后标记法测量芳香族加合物。使用 Cox 比例风险模型和改良部分似然法估计 DNA 加合物与肺癌风险之间的关联。当 DNA 加合物浓度增加一倍时，总体上肺癌发病风险显著增加，调整所有相关混杂因素后的相对风险（RR）为 1.36，95%置信区间（CI）为 1.18-157。对于当前吸烟者和工作中接触多环芳烃的受试者，当 DNA 加合物浓度增加一倍时，肺癌发病风险显著增加；男性的风险略高于女性。然而，在吸烟状况、性别或职业性多环芳烃暴露等方面，加合物水平的影响无统计学差异。一项荟萃分析综合了四项前瞻性研究，包括本研究，结果表明，在当前吸烟者中存在显著关联，当白细胞中芳香族 DNA 加合物水平增加一倍时，肺癌风险总体增加 34%。
