Nonspecific structural chromosomal aberrations (CAs) are found in around 1% of circulating lymphocytes from healthy individuals but the frequency may be higher after exposure to carcinogenic chemicals or radiation. CAs have been used in the monitoring of persons exposed to genotoxic agents and radiation. Previous studies on occupationally exposed individuals have shown associations between the frequency of CAs in peripheral blood lymphocytes and subsequent cancer risk. The cause for CA formation are believed to be unrepaired or insufficiently repaired DNA double-strand breaks or other DNA damage, and additionally telomere shortening. CAs include chromosome (CSAs) and chromatid type aberrations (CTAs). In the present review, we first describe the types of CAs, the conventional techniques used for their detection and some aspects of interpreting the results. We then focus on germline genetic variation in the frequency and type of CAs measured in a genome-wide association study (GWAS) in healthy individuals in relation to occupational and smoking-related exposure compared to non-exposed referents. The associations (at p<10-5) on 1473 healthy individuals were broadly classified in candidate genes from functional pathways related to DNA damage response/repair, including PSMA1, UBR5, RRM2B, PMS2P4, STAG3L4, BOD1, COPRS and FTO; another group included genes related to apoptosis, cell proliferation, angiogenesis and tumorigenesis, COPB1, NR2C1, COPRS, RHOT1, ITGB3, SYK, and SEMA6A; a third small group mapped to genes KLF7, SEMA5A and ITGB3 which were related to autistic traits, known to manifest frequent CAs. Dedicated studies on 153 DNA repair genes showed associations for some 30 genes, expression of which could be modified by the implicated variants. We finally point out that monitoring of CAs is so far the only method of assessing cancer risk in healthy human populations, and the use of the technology should be made more attractive by developing automated performance steps and incorporating artificial intelligence methods into the scoring.

中文翻译：

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非特异性染色体畸变的遗传和环境关联

健康个体约 1% 的循环淋巴细胞中发现非特异性染色体结构畸变 (CA)，但在接触致癌化学物质或辐射后，出现频率可能会更高。CA 已用于监测暴露于基因毒剂和辐射的人员。先前对职业暴露个体的研究表明，外周血淋巴细胞中 CA 的频率与随后的癌症风险之间存在关联。CA 形成的原因被认为是未修复或修复不充分的 DNA 双链断裂或其他 DNA 损伤，以及端粒缩短。CA 包括染色体 (CSA) 和染色单体类型畸变 (CTA)。在本综述中，我们首先描述 CA 的类型、用于检测它们的传统技术以及解释结果的一些方面。然后，我们将重点放在全基因组关联研究 (GWAS) 中测量的健康个体中 CA 频率和类型的种系遗传变异，与职业和吸烟相关暴露相比，与非暴露参考对象相比。1473 名健康个体的关联（p<10-5）被广泛分类为来自与 DNA 损伤反应/修复相关的功能途径的候选基因，包括 PSMA1、UBR5、RRM2B、PMS2P4、STAG3L4、BOD1、COPRS 和 FTO；另一组包括与细胞凋亡、细胞增殖、血管生成和肿瘤发生相关的基因，COPB1、NR2C1、COPRS、RHOT1、ITGB3、SYK和SEMA6A；第三小组映射到基因 KLF7、SEMA5A 和 ITGB3，这些基因与自闭症特征相关，已知会表现出频繁的 CA。对 153 个 DNA 修复基因的专门研究表明，大约 30 个基因之间存在关联，这些基因的表达可以通过所涉及的变异来改变。我们最后指出，迄今为止，监测 CA 是评估健康人群癌症风险的唯一方法，并且应该通过开发自动化执行步骤并将人工智能方法纳入评分来使该技术的使用更具吸引力。