Association of PARP1-specific polymorphisms and haplotypes with non-small cell lung cancer subtypes.
Adult
Aged
Aged, 80 and over
Alleles
Carcinoma, Non-Small-Cell Lung
/ classification
Case-Control Studies
Female
Gene Frequency
/ genetics
Genetic Predisposition to Disease
/ genetics
Genotype
Haplotypes
/ genetics
Humans
Linkage Disequilibrium
/ genetics
Lung Neoplasms
/ genetics
Male
Middle Aged
Poly (ADP-Ribose) Polymerase-1
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Prognosis
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
04
2020
accepted:
20
11
2020
entrez:
7
12
2020
pubmed:
8
12
2020
medline:
29
1
2021
Statut:
epublish
Résumé
The carcinogenesis role of PARP1 in lung cancer is still not clear. Analysis at allelic levels cannot fully explain the function of PARP1 on lung cancer. Our study aims to further explore the relation between PARP1 haplotypes and lung cancer. DNA and RNA were extracted from non-small cell lung cancer (NSCLC) tumor and adjacent normal fresh frozen tissue. Five PARP1-SNPs were genotyped and PARP1-specific SNPs were imputed using IMPUTE and SHAPEIT software. The SNPs were subjected to allelic, haplotype and SNP-SNP interaction analyses. Correlation between SNPs and mRNA/protein expressions were performed. SNP imputation inferred the ungenotyped SNPs and increased the power for association analysis. Tumor tissue samples are more likely to carry rs1805414 (OR = 1.85; 95% CI: 1.12-3.06; P-value: 0.017) and rs1805404 (OR = 2.74; 95%CI 1.19-6.32; P-value: 0.015) compared to normal tissues. Our study is the first study to show that haplotypes comprising of 5 SNPs on PARP1 (rs1136410, rs3219073, rs1805414, rs1805404, rs1805415) is able to differentiate the NSCLC tumor from normal tissues. Interaction between rs3219073, rs1805415, and rs1805414 were significantly associated with the NSCLC tumor with OR ranging from 3.61-6.75; 95%CI from 1.82 to 19.9; P-value<0.001. PARP1 haplotypes may serve as a better predictor in lung cancer development and prognosis compared to single alleles.
Identifiants
pubmed: 33284833
doi: 10.1371/journal.pone.0243509
pii: PONE-D-20-11416
pmc: PMC7721167
doi:
Substances chimiques
PARP1 protein, human
EC 2.4.2.30
Poly (ADP-Ribose) Polymerase-1
EC 2.4.2.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0243509Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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