Distinct pathways associated with chromosomal aberration frequency in a cohort exposed to genotoxic compounds compared to general population

• DOI: 10.1093/mutage/gez024
• Publication Date: 2019-08-20T19:16:39Z
• Authors: Yasmeen Niazi; Hauke Thomsen; Bozena Smolkova; Ludmila Vodickova; Soňa Vodenkova; Michal Kroupa; Veronika Vymetalkova; Alena Kazimirova; Magdalena Baranco...; Katarina Volkovova; Marta Staruchova; Per Hoffmann; Markus M Nöthen; Maria Dusinska; Ludovit Musak; Pavel Vodicka; Kari Hemminki; Asta Försti
• Keywords: Chromosome aberration; Genome-wide Association Study; Genetic Association; Chromosome instability

Abstract Non-specific structural chromosomal aberrations (CAs) observed in peripheral blood lymphocytes of healthy individuals can be either chromosome-type (CSAs) or chromatid-type (CTAs) depending on the stage cell division they are induced and mechanism formation. It is important to study genetic basis instability as it a marker genotoxic exposure predictor cancer risk. For that purpose, we conducted two genome-wide association studies (GWASs) presence absence apparent from Czech Republic Slovakia. The pre-GWAS cytogenetic analysis reported frequencies CSA, CTA total CA (CAtot). We performed both linear binary logistic regression with an arbitrary cut-off point 2% for CAtot 1% CSA CTA. Using statistical threshold 1.0 × 10−5, identified five loci silico predicted functionality reference group four exposed group, no overlap between associated regions. A meta-analysis GWASs further moderate associations each studies. From mainly within genes related DNA damage response/repair were identified. Other groups found involved segregation chromosomes chromatin modification. Some discovered regions implicated tumourigenesis autism.