Base Excision Repair Gene Polymorphisms and Wilms Tumor Susceptibility
Jinhong Zhu,
Wei Jia,
Caixia Wu,
Wen Fu,
Huimin Xia,
Guochang Liu,
Jing He
Affiliations
Jinhong Zhu
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Clinical Laboratory, Molecular Epidemiology Laboratory, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China
Wei Jia
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
Caixia Wu
Department of Oncology, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China
Wen Fu
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
Huimin Xia
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China
Guochang Liu
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Correspondence to: Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Jing He
Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Correspondence to: Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, 9 Jinsui Road, Guangzhou 510623, Guangdong, China.
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. Keywords: Base excision repair, DNA repair, Polymorphisms, Wilms tumor, Susceptibility
