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生活方式、环境和遗传因素对前瞻性丹麦队列研究人群中大量 DNA 加合物的预测作用。

Lifestyle, environmental, and genetic predictors of bulky DNA adducts in a study population nested within a prospective Danish cohort.

机构信息

Danish Cancer Society, Institute of Cancer Epidemiology, Copenhagen, Denmark.

出版信息

J Toxicol Environ Health A. 2010;73(9):583-95. doi: 10.1080/15287390903566633.

Abstract

Bulky DNA adducts are considered a potential biomarker of cancer risk. In this study, the association between various lifestyle, environmental, and genetic factors and the levels of bulky DNA adducts in peripheral leukocytes was examined in a study group nested within a population-based prospective Danish cohort. At enrollment, blood samples were collected and information on lifestyle, including dietary and smoking habits, obtained. Previously, bulky DNA adducts were measured in 245 individuals who developed lung cancer and 255 control members of the cohort. Of these 500 individuals, data on 375 individuals were included in this study, excluding 125 cases, which developed lung cancer within the first 3 yr after blood sampling. Bulky DNA adduct levels were measured by 32P-postlabeling technique and polymorphisms in carcinogen metabolism and DNA repair genes were determined. Potential predictors of bulky DNA adduct levels were analyzed by univariate and multivariate regression analyses. Women tended to have higher adduct levels than men. Living in central Copenhagen and surface darkness of fried meat and fish were associated with quantitative higher adduct levels. No significant associations were found between dietary factors or smoking and DNA adduct levels. Further, the results showed no prominent associations between any of 12 genetic polymorphisms and adduct levels. Overall, our study showed only few associations between dietary, environmental, and genetic factors and levels of bulky DNA adducts measured in peripheral leukocytes in a general Danish population.

摘要

大量 DNA 加合物被认为是癌症风险的一个潜在生物标志物。在这项研究中,在一个基于人群的前瞻性丹麦队列中嵌套的研究组中,研究了各种生活方式、环境和遗传因素与外周白细胞中大量 DNA 加合物水平之间的关联。在入组时采集了血样,并获得了生活方式信息,包括饮食和吸烟习惯。此前,在 245 名患有肺癌的个体和队列的 255 名对照成员中测量了大量 DNA 加合物。在这 500 名个体中,本研究纳入了其中 375 名个体的数据,排除了 125 名在采血后 3 年内发生肺癌的病例。大量 DNA 加合物水平通过 32P-后标记技术测量,并确定了致癌物质代谢和 DNA 修复基因的多态性。通过单变量和多变量回归分析分析了大量 DNA 加合物水平的潜在预测因子。女性的加合物水平往往高于男性。居住在哥本哈根市中心和油炸肉和鱼的表面黑暗度与定量更高的加合物水平有关。饮食因素或吸烟与 DNA 加合物水平之间没有显著关联。此外,结果显示,12 种遗传多态性与加合物水平之间没有明显的关联。总的来说,我们的研究仅显示了在一般丹麦人群中,饮食、环境和遗传因素与外周白细胞中大量 DNA 加合物水平之间存在少数关联。

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