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

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Genetic variation associated with chromosomal aberration frequency : A genome-wide association study. / Niazi, Yasmeen; Thomsen, Hauke; Smolkova, Bozena; Vodickova, Ludmila; Vodenkova, Sona; Kroupa, Michal; Vymetalkova, Veronika; Kazimirova, Alena; Barancokova, Magdalena; Volkovova, Katarina; Staruchova, Marta; Hoffmann, Per; Nöthen, Markus M.; Dušinská, Maria; Musak, Ludovit; Vodicka, Pavel; Hemminki, Kari; Försti, Asta.

In: Environmental and Molecular Mutagenesis, 03.10.2018.

Research output: Contribution to journalArticle

Harvard

Niazi, Y, Thomsen, H, Smolkova, B, Vodickova, L, Vodenkova, S, Kroupa, M, Vymetalkova, V, Kazimirova, A, Barancokova, M, Volkovova, K, Staruchova, M, Hoffmann, P, Nöthen, MM, Dušinská, M, Musak, L, Vodicka, P, Hemminki, K & Försti, A 2018, 'Genetic variation associated with chromosomal aberration frequency: A genome-wide association study', Environmental and Molecular Mutagenesis. https://doi.org/10.1002/em.22236

APA

CBE

Niazi Y, Thomsen H, Smolkova B, Vodickova L, Vodenkova S, Kroupa M, Vymetalkova V, Kazimirova A, Barancokova M, Volkovova K, Staruchova M, Hoffmann P, Nöthen MM, Dušinská M, Musak L, Vodicka P, Hemminki K, Försti A. 2018. Genetic variation associated with chromosomal aberration frequency: A genome-wide association study. Environmental and Molecular Mutagenesis. https://doi.org/10.1002/em.22236

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Niazi, Yasmeen ; Thomsen, Hauke ; Smolkova, Bozena ; Vodickova, Ludmila ; Vodenkova, Sona ; Kroupa, Michal ; Vymetalkova, Veronika ; Kazimirova, Alena ; Barancokova, Magdalena ; Volkovova, Katarina ; Staruchova, Marta ; Hoffmann, Per ; Nöthen, Markus M. ; Dušinská, Maria ; Musak, Ludovit ; Vodicka, Pavel ; Hemminki, Kari ; Försti, Asta. / Genetic variation associated with chromosomal aberration frequency : A genome-wide association study. In: Environmental and Molecular Mutagenesis. 2018.

RIS

TY - JOUR

T1 - Genetic variation associated with chromosomal aberration frequency

T2 - Environmental and Molecular Mutagenesis

AU - Niazi, Yasmeen

AU - Thomsen, Hauke

AU - Smolkova, Bozena

AU - Vodickova, Ludmila

AU - Vodenkova, Sona

AU - Kroupa, Michal

AU - Vymetalkova, Veronika

AU - Kazimirova, Alena

AU - Barancokova, Magdalena

AU - Volkovova, Katarina

AU - Staruchova, Marta

AU - Hoffmann, Per

AU - Nöthen, Markus M.

AU - Dušinská, Maria

AU - Musak, Ludovit

AU - Vodicka, Pavel

AU - Hemminki, Kari

AU - Försti, Asta

PY - 2018/10/3

Y1 - 2018/10/3

N2 - 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.

AB - 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.

KW - chromatid-type aberrations

KW - chromosome-type aberrations

KW - GWAS

KW - single-nucleotide polymorphism

UR - http://www.scopus.com/inward/record.url?scp=85055711280&partnerID=8YFLogxK

U2 - 10.1002/em.22236

DO - 10.1002/em.22236

M3 - Article

JO - Environmental and Molecular Mutagenesis

JF - Environmental and Molecular Mutagenesis

SN - 1098-2280

ER -