Base Excision Repair Gene Polymorphisms and Wilms Tumor Susceptibility

Autor: Guochang Liu, Jinhong Zhu, Wen Fu, Wei Jia, Caixia Wu, Huimin Xia, Jing He
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Oncology
XRCC1
x-ray repair cross-complementing group 1
DNA Repair
lcsh:Medicine
LIG3
ligase III
XRCC1
0302 clinical medicine
Medicine
PARP1
poly ADP-ribose polymerase 1
BER
base excision repair
lcsh:R5-920
hOGG1
human 8-oxoguanine DNA glycosylase
HWE
Hardy-Weinberg equilibrium
GTEx
Genotype-Tissue Expression
General Medicine
SNP
single nucleotide polymorphism
WT1
Wilms tumor gene 1
UTR
untranslated region
030220 oncology & carcinogenesis
eQTL
expression quantitative trait loci
TP53
tumor protein 53
lcsh:Medicine (General)
Research Paper
Premature aging
medicine.medical_specialty
LD
linkage disequilibrium
Single-nucleotide polymorphism
Quantitative trait locus
Polymorphism
Single Nucleotide
Wilms Tumor
General Biochemistry
Genetics and Molecular Biology
APEX1
apyrimidinic endonuclease 1
03 medical and health sciences
Internal medicine
Humans
Genetic Predisposition to Disease
Base excision repair
business.industry
lcsh:R
Case-control study
FEN1
Flap endonuclease 1
CDS
coding sequence
Wilms' tumor
Odds ratio
medicine.disease
APEX1
OR
odds ratio
CI
confidence interval
030104 developmental biology
Haplotypes
Susceptibility
business
Polymorphisms
Zdroj: EBioMedicine
EBioMedicine, Vol 33, Iss, Pp 88-93 (2018)
ISSN: 2352-3964
Popis: Base excision repair (BER) is the main mechanism to repair endogenous DNA lesions caused by reactive oxygen species. BER deficiency is linked with cancer susceptibility and premature aging. Single nucleotide polymorphisms (SNPs) within BER genes have been implicated in various human malignancies. Nevertheless, a comprehensive investigation of their association with Wilms tumor susceptibility is lacking. In this study, 145 cases and 531 sex and age-matched healthy controls were recruited. We systematically genotyped 18 potentially functional SNPs in six core BER pathway genes, using a candidate SNP approach. Logistic regression was employed to evaluate odds ratio (OR) and 95% confidence interval (CI) adjusted for age and gender. Several SNPs showed protective effects against Wilms tumor. Significant associations with Wilms tumor susceptibility were shown for hOGG1 rs1052133 (dominant: adjusted OR = 0.66, 95% CI = 0.45–0.96, P = .030), FEN1 rs174538 (dominant: adjusted OR = 0.66, 95% CI = 0.45–0.95, P = .027; recessive: adjusted OR = 0.54, 95% CI = 0.32–0.93 P = .027), and FEN1 rs4246215 (dominant: adjusted OR = 0.55, 95% CI = 0.38–0.80, P = .002) polymorphisms. Stratified analysis was performed by age, gender, and clinical stage. Moreover, there was evidence of functional implication of these significant SNPs suggested by online expression quantitative trait locus (eQTL) analysis. Our findings indicate that common SNPs in BER genes modify susceptibility to Wilms tumor.
Highlights • Numerous studies demonstrated association between BER gene SNPs and cancer susceptibility. However, the linkage between BER SNPs and Wilms tumor susceptibility has not been reported. We investigated 18 BER gene SNPs in 145 Wilms tumor cases and 531 healthy controls. Significant associations with decreased Wilms tumor susceptibility were observed for the hOGG1 rs1052133, FEN1 rs174538, and rs4246215 polymorphisms. eQTL analysis suggested potential functional implications for the significant polymorphisms. This is the most comprehensive investigations on the association between the BER polymorphisms and Wilms tumor susceptibility. Our findings support the potential protective role of these SNPs in Wilms tumor.
Databáze: OpenAIRE
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