Genetic variation associated with chromosomal aberration frequency: A genome-wide association study.
Adult
Autistic Disorder
/ genetics
Chromosome Aberrations
/ statistics & numerical data
Cytogenetic Analysis
Czech Republic
DNA Damage
/ genetics
DNA Repair
/ genetics
Down Syndrome
/ genetics
Female
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
Humans
Male
Middle Aged
Neoplasms
/ etiology
Polymorphism, Single Nucleotide
/ genetics
Promoter Regions, Genetic
/ genetics
Slovakia
GWAS
chromatid-type aberrations
chromosome-type aberrations
single-nucleotide polymorphism
Journal
Environmental and molecular mutagenesis
ISSN: 1098-2280
Titre abrégé: Environ Mol Mutagen
Pays: United States
ID NLM: 8800109
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
14
03
2018
revised:
18
05
2018
accepted:
03
07
2018
pubmed:
29
10
2018
medline:
15
2
2019
entrez:
29
10
2018
Statut:
ppublish
Résumé
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
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
17-28Informations de copyright
© 2018 Wiley Periodicals, Inc.