BARD1 Gene Polymorphisms Confer Nephroblastoma Susceptibility.
BRCA1-associated RING domain protein 1 (BARD1) is a tumor suppressor, which forms a heterodimer with BRCA1. Three BARD1 gene polymorphisms (rs7585356 G>A, rs6435862 T>G and rs3768716 A>G) were initially identified as high-risk neuroblastoma susceptibility loci by a previous GWAS. Because of the general tumor-suppressing function of BARD1, we hypothesized that these BARD1 gene polymorphisms might modify the susceptibility to nephroblastoma. We genotyped these polymorphisms in 145 cases and 531 controls using Taqman methods. Out of three polymorphisms, only the rs7585356 G>A polymorphism was significantly associated with increased susceptibility to nephroblastoma [AA vs. GG: adjusted odds ratio (OR)=1.78, 95% confidence interval (CI)=1.01-3.12]. Combined analysis of three polymorphisms indicated that subjects with 3 risk genotypes exhibited significantly elevated nephroblastoma risk, when compared with subjects with 0-2 risk genotypes (adjusted OR=1.72, 95% CI=1.02-2.89). Stratified analysis revealed that in term of clinical stage, rs7585356 AA carriers were associated with increased risk of developing clinical stage I+II nephroblastoma. The presence of three risk genotypes was significantly associated with nephroblastoma risk in females and clinical stage I+II nephroblastoma. Our results suggested that BARD1 rs7585356 G>A may be associated with nephroblastoma risk.
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Wen
W
Fu
Molecular Epidemiology Laboratory and Department of Laboratory Medicine, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
Jinhong
J
Zhu
Department of Urology, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou 510180, Guangdong, China.
Si-Wei
SW
Xiong
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Wei
W
Jia
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Zhang
Z
Zhao
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Shi-Bo
SB
Zhu
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Jin-Hua
JH
Hu
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Feng-Hua
FH
Wang
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
Huimin
H
Xia
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China. Electronic address: hejing198374@gmail.com.
Jing
J
He
Department of Pediatric Urology, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China. Electronic address: starbless2003@126.com.
Guo-Chang
GC
Liu
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D009396:Wilms Tumor / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
D025521:Tumor Suppressor Proteins; C102449:BARD1 protein, human; D044767:Ubiquitin-Protein Ligases
BARD1; Nephroblastoma; Polymorphisms; Susceptibility