Impact of types of lymphocyte chromosomal aberrations on human cancer risk:: Results from Nordic and Italian cohorts
Impact of types of lymphocyte chromosomal aberrations on human cancer risk:: Results from Nordic and Italian cohorts
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DOI：
10.1158/0008-5472.can-03-3360
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发表时间：
2004-03-15
期刊：
影响因子：
11.2
通讯作者：
Norppa, H
中科院分区：
文献类型：
--
作者：
Hagmar, L;Strömberg, U;Norppa, H
外周血淋巴细胞中具有结构性染色体畸变（CAs）的细胞频率是首个已显示与癌症风险相关的遗传毒性生物标志物。CAs通常分为染色体型（CSAs）和染色单体型畸变（CTAs），它们具有不同的形成机制。从机制的角度来看，阐明CAs对癌症的预测性在CSAs和CTAs方面是否不同是很有意义的。我们在此报告了经过细胞遗传学检测的健康受试者的癌症风险，涉及外周血淋巴细胞中CAs、CSAs和CTAs的频率，使用了北欧（1981名有CA数据的受试者，1871名有CSA/CTA数据的受试者）和意大利（1573名有CA数据的受试者，877名有CTA/CSA数据的受试者）队列，中位随访时间为17年。检测时CAs水平高显然与北欧队列中总癌症发病率增加以及意大利队列中总癌症死亡率增加相关。在北欧队列中，检测时CSAs和CTAs均高的受试者癌症风险显著升高，并且这些变量显示出同样强的癌症预测性。意大利队列的结果未表明CSA和CTA生物标志物在癌症预测性方面有任何明显差异。检测时的年龄、性别、国家或检测后的时间对结果没有显著的影响修饰作用。结果表明，导致CSAs和CTAs的DNA双链断裂以及其他初始DNA损伤都与癌症风险相关。
The frequency of cells with structural chromosomal aberrations (CAs) in peripheral blood lymphocytes is the first genotoxicity biomarker that has shown an association with cancer risk. CAs are usually divided into chromosome-type (CSAs) and chromatid-type aberrations (CTAs), with different mechanisms of formation. From a mechanistic point of view, it is of interest to clarify whether the cancer predictivity of CAs is different with respect to CSAs and CTAs. We report here cancer risk for cytogenetically tested, healthy subjects with respect to frequency of CAs, CSAs, and CTAs in peripheral blood lymphocytes, using Nordic (1981 subjects with CA data, 1871 subjects with CSA/CTA data) and Italian (1573 subjects with CA data, 877 subjects with CTA/CSA data) cohorts, with a median follow-up of 17 years. High levels of CAs at test were clearly associated with increased total cancer incidence in the Nordic cohorts and increased total cancer mortality in the Italian cohort. In the Nordic cohorts, significantly elevated cancer risks were observed for subjects with both high CSAs and high CTAs at test, and these variables showed equally strong cancer predictivity. The results of the Italian cohort did not indicate any clear-cut difference in cancer predictivity between the CSA and CTA biomarkers. There was no significant effect modification by age at test, gender, country, or time since test. The results suggest that both DNA double-strand breaks and other initial DNA lesions responsible for CSAs and CTAs are associated with cancer risk.