Lando C, Hagmar L, Bonassi S
Med Lav. 1998 Mar-Apr;89(2):124-31.
Cytogenetic assays in peripheral blood lymphocytes (PBL) have been used extensively in the last decades to survey human exposure to genotoxic agents. The conceptual basis for this approach has been the hypothesis that the extent of genetic damage in PBL reflects critical events for carcinogenic processes in target tissues. The predictive value of these tests for subsequent cancer risk has been recently evaluated by two cohort studies of cancer mortality and incidence carried out in Italy and in five North European countries. In this paper we report the update of both cohorts. In the new follow-up, a total of 64 cancer deaths out of 2019 subjects in the Italian cohort and 127 new cases of cancer out of 3182 subjects in the Nordic cohort were observed. The cytogenetic endpoints studied were CA (chromosomal aberrations), SCE (sister chromatid exchanges) and MN (micronuclei). In order to take into account the interlaboratory variation of absolute values, the results were trichotomized within each laboratory into three strata: low (1-33 percentile), medium (34-66 percentile), or high (67-100 percentile). The association between chromosomal damage and cancer risk was evaluated through SMR (standardized mortality ratio) for Italy and SIR (standardized incidence ratio) for the Nordic countries. National mortality/incidence cancer rates (age, sex and calendar-year specific) were used as reference. A linear trend of SMRs and SIRs according to CA level was found in both cohorts for the "All Cancers" cause (p < 0.01). In the Italian cohort it was also possible to analyze some specific cancer sites: a significant increase of SMR among subjects with a high level of CA with respect to the general population was found for lung cancers and lymphatic and hematopoietic tissue cancers. Contrariwise, no association between cancer mortality/incidence and SCE or MN frequency was observed. Findings from this study support the existence of an association between CA frequency and cancer risk.
在过去几十年中,外周血淋巴细胞(PBL)的细胞遗传学检测被广泛用于调查人类对遗传毒性剂的暴露情况。这种方法的概念基础是这样一种假设,即PBL中的遗传损伤程度反映了靶组织致癌过程中的关键事件。最近,意大利和五个北欧国家进行的两项关于癌症死亡率和发病率的队列研究评估了这些检测对后续癌症风险的预测价值。在本文中,我们报告了这两个队列的最新情况。在新的随访中,意大利队列的2019名受试者中有64例癌症死亡,北欧队列的3182名受试者中有127例新癌症病例。所研究的细胞遗传学终点包括染色体畸变(CA)、姐妹染色单体交换(SCE)和微核(MN)。为了考虑实验室间绝对值的差异,每个实验室的结果被分为三个层次:低(第1 - 33百分位数)、中(第34 - 66百分位数)或高(第67 - 100百分位数)。通过意大利的标准化死亡率(SMR)和北欧国家的标准化发病率(SIR)评估染色体损伤与癌症风险之间的关联。以国家癌症死亡率/发病率(按年龄、性别和历年划分)作为参考。在两个队列中,“所有癌症”病因的SMR和SIR均呈现出随CA水平的线性趋势(p < 0.01)。在意大利队列中,还能够分析一些特定的癌症部位:在CA水平高的受试者中,肺癌以及淋巴和造血组织癌症的SMR相对于一般人群显著增加。相反,未观察到癌症死亡率/发病率与SCE或MN频率之间存在关联。本研究结果支持CA频率与癌症风险之间存在关联。