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

Niazi, Yasmeen; Thomsen, Hauke LU ; Smolkova, Bozena; Vodickova, Ludmila; Vodenkova, Sona; Kroupa, Michal; Vymetalkova, Veronika; Kazimirova, Alena; Barancokova, Magdalena and Volkovova, Katarina, et al. (2018) In Environmental and Molecular Mutagenesis
Abstract

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... (More)

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 10−5 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. 2018 Wiley Periodicals, Inc.

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keywords
chromatid-type aberrations, chromosome-type aberrations, GWAS, single-nucleotide polymorphism
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Environmental and Molecular Mutagenesis
publisher
John Wiley & Sons
external identifiers
  • scopus:85055711280
ISSN
0893-6692
DOI
10.1002/em.22236
language
English
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yes
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723100d3-ea0b-447e-bc57-e54adbe60afc
date added to LUP
2018-11-08 09:53:02
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2019-02-20 11:34:50
@article{723100d3-ea0b-447e-bc57-e54adbe60afc,
  abstract     = {<p>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<sup>−5</sup> 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. 2018 Wiley Periodicals, Inc.</p>},
  author       = {Niazi, Yasmeen and Thomsen, Hauke and Smolkova, Bozena and Vodickova, Ludmila and Vodenkova, Sona and Kroupa, Michal and Vymetalkova, Veronika and Kazimirova, Alena and Barancokova, Magdalena and Volkovova, Katarina and Staruchova, Marta and Hoffmann, Per and Nöthen, Markus M. and Dušinská, Maria and Musak, Ludovit and Vodicka, Pavel and Hemminki, Kari and Försti, Asta},
  issn         = {0893-6692},
  keyword      = {chromatid-type aberrations,chromosome-type aberrations,GWAS,single-nucleotide polymorphism},
  language     = {eng},
  month        = {10},
  publisher    = {John Wiley & Sons},
  series       = {Environmental and Molecular Mutagenesis},
  title        = {Genetic variation associated with chromosomal aberration frequency : A genome-wide association study},
  url          = {http://dx.doi.org/10.1002/em.22236},
  year         = {2018},
}