Hagmar L, Bonassi S, Strömberg U, Mikoczy Z, Lando C, Hansteen I L, Montagud A H, Knudsen L, Norppa H, Reuterwall C, Tinnerberg H, Brogger A, Forni A, Högstedt B, Lambert B, Mitelman F, Nordenson I, Salomaa S, Skerfving S
Department of Occupational and Environmental Medicine, Lund University, S-221 85, Lund, Sweden.
Mutat Res. 1998 Sep 20;405(2):171-8. doi: 10.1016/s0027-5107(98)00134-1.
The cytogenetic endpoints in peripheral blood lymphocytes: chromosomal aberrations (CA), sister chromatid exchange (SCE) and micronuclei (MN) are established biomarkers of exposure for mutagens or carcinogens in the work environment. However, it is not clear whether these biomarkers also may serve as biomarkers for genotoxic effects which will result in an enhanced cancer risk. In order to assess this problem, Nordic and Italian cohorts were established, and preliminary results from these two studies indicated a predictive value of CA frequency for cancer risk, whereas no such associations were observed for SCE or MN. A collaborative study between the Nordic and Italian research groups, will enable a more thorough evaluation of the cancer predictivity of the cytogenetic endpoints. We here report on the establishment of a joint data base comprising 5271 subjects, examined 1965-1988 for at least one cytogenetic biomarker. Totally, 3540 subjects had been examined for CA, 2702 for SCE and 1496 for MN. These cohorts have been followed-up with respect to subsequent cancer mortality or cancer incidence, and the expected values have been calculated from rates derived from the general populations in each country. Stratified cohort analyses will be performed with respect to the levels of the cytogenetic biomarkers. The importance of potential effect modifiers such as gender, age at test, and time since test, will be evaluated using Poisson regression models. The remaining two potential effect modifiers, occupational exposures and smoking, will be assessed in a case-referent study within the study base.
染色体畸变(CA)、姐妹染色单体交换(SCE)和微核(MN)是工作环境中诱变剂或致癌物暴露的既定生物标志物。然而,尚不清楚这些生物标志物是否也可作为遗传毒性效应的生物标志物,而这种效应会导致癌症风险增加。为了评估这一问题,建立了北欧和意大利队列,这两项研究的初步结果表明CA频率对癌症风险具有预测价值,而未观察到SCE或MN有此类关联。北欧和意大利研究小组之间的合作研究将能够更全面地评估细胞遗传学终点的癌症预测性。我们在此报告建立了一个包含5271名受试者的联合数据库,这些受试者在1965 - 1988年期间至少接受了一种细胞遗传学生物标志物的检测。总共有3540名受试者接受了CA检测,2702名接受了SCE检测,1496名接受了MN检测。对这些队列进行了后续癌症死亡率或癌症发病率的随访,并根据每个国家一般人群的发病率计算了预期值。将根据细胞遗传学生物标志物的水平进行分层队列分析。将使用泊松回归模型评估潜在效应修饰因素(如性别、检测时年龄和检测后的时间)的重要性。其余两个潜在效应修饰因素,即职业暴露和吸烟,将在研究库中的病例对照研究中进行评估。