Base Excision Repair Gene Polymorphisms and Wilms Tumor Susceptibility

Area of Science:

• Genetics
• Molecular Biology
• Oncology

Background:

• Base excision repair (BER) is crucial for repairing DNA damage from reactive oxygen species.
• BER deficiency is linked to cancer susceptibility and premature aging.
• Single nucleotide polymorphisms (SNPs) in BER genes are implicated in various cancers, but their role in Wilms tumor is understudied.

Purpose of the Study:

• To investigate the association between common functional SNPs in core BER genes and Wilms tumor susceptibility.
• To identify specific SNPs that may confer a protective effect against Wilms tumor development.

Main Methods:

• Genotyping of 18 potentially functional SNPs in six core BER pathway genes in 145 Wilms tumor cases and 531 controls.
• Logistic regression analysis to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI).
• Stratified analyses by age, gender, and clinical stage, alongside expression quantitative trait locus (eQTL) analysis.

Main Results:

• SNPs in hOGG1 (rs1052133) and FEN1 (rs174538, rs4246215) were significantly associated with reduced Wilms tumor susceptibility.
• Dominant and recessive models showed protective effects for FEN1 rs174538, and a dominant model for hOGG1 rs1052133 and FEN1 rs4246215.
• eQTL analysis provided evidence for the functional relevance of these associated SNPs.

Conclusions:

• Common SNPs in BER genes, specifically hOGG1 and FEN1, appear to modify susceptibility to Wilms tumor.
• These findings highlight the role of DNA repair genetic variations in pediatric cancer risk.
• Further research into BER pathway genetics could inform personalized cancer risk assessment.