Genetic variation associated with chromosomal aberration frequency: A genome-wide association study.

Authors:
Hauke Thomsen, Dr.
Hauke Thomsen, Dr.
GeneWerk GmbH
Senior Bioinformatician
Bioinformatics, Biostatistics, Genetics
Heidelberg, Baden-Württemberg/Germany | Germany
Ludmila Vodickova
Ludmila Vodickova
Institute of Experimental Medicine
Czech Republic
Sona Vodenkova
Sona Vodenkova
Institute of Experimental Medicine
Prague | Czech Republic
Veronika Vymetalkova
Veronika Vymetalkova
Charles University
Czechia
Alena Kazimirova
Alena Kazimirova
Slovak Medical University

Environ Mol Mutagen 2019 01 3;60(1):17-28. Epub 2018 Oct 3.

Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120, Heidelberg, Germany.

Chromosomal aberrations (CAs) in human peripheral blood lymphocytes (PBL) measured with the conventional cytogenetic assay have been used for human biomonitoring of genotoxic exposure for decades. CA frequency in peripheral blood is a marker of cancer susceptibility. Previous studies have shown associations between genetic variants in metabolic pathway, DNA repair and major mitotic checkpoint genes and CAs. We conducted a genome-wide association study on 576 individuals from the Czech Republic and Slovakia followed by a replication in two different sample sets of 482 (replication 1) and 1288 (replication 2) samples. To have a broad look at the genetic susceptibility associated with CA frequency, the sample sets composed of individuals either differentially exposed to smoking, occupational/environmental hazards, or they were untreated cancer patients. Phenotypes were divided into chromosome- and chromatid-type aberrations (CSAs and CTAs, respectively) and total chromosomal aberrations (CAtot). The arbitrary cutoff point between individuals with high and low CA frequency was 2% for CAtot and 1% for CSA and CTA. The data were analyzed using age, sex, occupation/cancer and smoking history as covariates. Altogether 11 loci reached the P-value of 10 in the GWAS. Replication 1 supported the association of rs1383997 (8q13.3) and rs2824215 (21q21.1) in CAtot and rs983889 (5p15.1) in CTA analysis. These loci were found to be associated with genes involved in mitosis, response to environmental and chemical factors and genes involved in syndromes linked to chromosomal abnormalities. Identification of new genetic variants for the frequency of CAs offers prediction tools for cancer risk in future. Environ. Mol. Mutagen. 60:17-28, 2019. © 2018 Wiley Periodicals, Inc.

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http://doi.wiley.com/10.1002/em.22236
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January 2019
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References

(Supplied by CrossRef)
From DNA damage to chromosome aberrations: Joining the break
Durante et al.
Mutat. Res. Toxicol. Environ. Mutagen. 2013

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