Genomic instability is a characteristic of a majority of human malignancies. Chromosomal instability is a common form of genomic instability that can be caused by defects in mitotic checkpoint genes. Chromosomal aberrations in peripheral blood are also indicative of genotoxic exposure and potential cancer risk. We evaluated associations between inherited genetic variants in 33 mitotic checkpoint genes and the frequency of chromosomal aberrations (CAs) in the presence and absence of environmental genotoxic exposure. Associations with both chromosome and chromatid type of aberrations were evaluated in two cohorts of healthy individuals, namely an exposed and a reference group consisting of 607 and 866 individuals, respectively. Binary logistic and linear regression analyses were performed for the association studies. Bonferroni-corrected significant p-value was 5 × 10^-4 for 99 tests based on the number of analyzed genes and phenotypes. In the reference group the most prominent associations were found with variants in CCNB1, a master regulator of mitosis, and in genes involved in kinetochore function, including CENPH and TEX14, whereas in the exposed group the main association was found with variants in TTK, also an important gene in kinetochore function. How the identified variants may affect the fidelity of mitotic checkpoint remains to be investigated, however, the present study suggests that genetic variation may partly explain interindividual variation in the formation of CAs.

基因组不稳定性是大多数人类恶性肿瘤的特征。染色体不稳定性是基因组不稳定性的一种常见形式，可由有丝分裂检查点基因的缺陷引起。外周血中的染色体畸变也预示着遗传毒性暴露和潜在的癌症风险。我们评估了 33 个有丝分裂检查点基因中遗传变异与染色体畸变 (CA) 频率之间的关联，在存在和不存在环境遗传毒性暴露的情况下。在两组健康个体中评估了与染色体和染色单体类型畸变的关联，即分别由 607 和 866 个人组成的暴露组和参考组。对关联研究进行二元逻辑和线性回归分析。^-4用于基于分析的基因和表型的数量的 99 次测试。在参照组中最显着的关联被发现与在变体CCNB1，有丝分裂的主调节器，并在参与着丝粒功能，包括基因CENPH和TEX14，而暴露的组中的主要关联用在变体中发现TTK，也动粒功能中的一个重要基因。鉴定的变异如何影响有丝分裂检查点的保真度仍有待研究，然而，本研究表明遗传变异可能部分解释了 CA 形成中的个体间变异。