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工作场所中的染色体损伤与癌症风险:以克罗地亚的细胞遗传学监测为例。

Chromosome damage and cancer risk in the workplace: the example of cytogenetic surveillance in Croatia.

作者信息

Fucić Aleksandra, Znaor Ariana, Strnad Marija, van der Hel Olga, Aleksandrov Anastasija, Miskov Snjezana, Grah Josip, Sedlar Miljenko, Jazbec Ana Marija, Ceppi Marcello, Vermeulen Roel, Boffetta Paolo, Norppa Hannu, Bonassi Stefano

机构信息

Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia.

出版信息

Toxicol Lett. 2007 Jul 30;172(1-2):4-11. doi: 10.1016/j.toxlet.2007.05.015. Epub 2007 May 25.

Abstract

The use of cytogenetic assays in the surveillance of populations occupationally exposed to genotoxic carcinogens originates from the assumption that chromosomal alterations might be causally involved in early stages of carcinogenesis. Historical cohort studies have since 1990s consistently reported an association between the level of chromosomal aberrations (CA) in peripheral lymphocytes of healthy subjects and the risk of cancer. Only in few cases, have these results been transformed into a regulatory tool for improving occupational safety. The cytogenetic surveillance program adopted for more than two decades in the Republic of Croatia is one of these few examples. Croatian workers exposed to genotoxic agents were systematically screened for CA, to identify occupational settings needing a priority intervention. Significant increases of mean CA frequency were observed in groups exposed to ionizing radiation, chemical agents, and mixed exposures when compared with a group of unexposed referents. CA data on 736 men and 584 women, monitored between 1987 and 2000, have been associated with cancer incidence. Although the small size of the cohort did not allow for reaching statistical significance, the medium tertile of the CA frequency distribution was associated with a doubling of cancer incidence rate ratio (IRR=2.40; 95% CI 0.85-6.77) when compared with the lowest tertile. For chromosome-type CA, IRR was non-significantly increased for both the medium (IRR 1.53, 95% CI 0.58-3.99) and high categories (IRR 1.69; 95% CI 0.61-4.72). Recommendations for future strategies comprise the inclusion of predictive biomarkers in surveillance programs, the definition of a regulatory framework, and their possible use for the identification of individual risk profiles.

摘要

细胞遗传学检测用于职业性接触遗传毒性致癌物人群的监测,其依据是染色体改变可能在致癌作用的早期阶段存在因果关系。自20世纪90年代以来,历史队列研究一直报告健康受试者外周血淋巴细胞中染色体畸变(CA)水平与癌症风险之间存在关联。只有在少数情况下,这些结果才转化为改善职业安全的监管工具。克罗地亚共和国二十多年来采用的细胞遗传学监测计划就是这少数例子之一。对接触遗传毒性剂的克罗地亚工人系统性地筛查CA,以确定需要优先干预的职业环境。与未接触的对照组相比,在接触电离辐射、化学剂和混合暴露的组中观察到平均CA频率显著增加。1987年至2000年期间监测的736名男性和584名女性的CA数据与癌症发病率相关。尽管队列规模较小无法达到统计学显著性,但与最低三分位数相比,CA频率分布的中间三分位数与癌症发病率比值加倍相关(发病率比值比[IRR]=2.40;95%可信区间0.85 - 6.77)。对于染色体型CA,中间(IRR 1.53,95%可信区间0.58 - 3.99)和高类别(IRR 1.69;95%可信区间0.61 - 4.72)的IRR均无显著增加。未来策略的建议包括在监测计划中纳入预测生物标志物、定义监管框架以及它们可能用于识别个体风险概况。

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