title: Single nucleotide polymorphism rs11669203 in TGFBR3L is associated with the risk of neuroblastoma in a Chinese population.
abstract: With a primary mortality, neuroblastoma (NB) is the most common extracranial solid tumor in childhood. Amplification of the MYCN (v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog) oncogene is observed in 20-30 % of NB cases, a feature which also characterizes a highly aggressive subtype of the disease. However, the systematic study of association between single nucleotide polymorphisms (SNPs) in MYCN-regulated genes and the risk of NB has not been investigated. In the current study, we scanned a set of 16 SNPs located within known or predicted MYCN binding sites in a cohort of 247 patients of Chinese origin with neuroblastic family tumors, including neuroblastoma (NB), ganglioneuroma (GN), and ganglioneuroblastoma (GNB), and in 290 cancer-free controls to determine whether any of the tested SNPs are associated with neuroblastic family tumors. We found that the rs11669203 G>C polymorphism, located in TGFBR3L promoter, is significantly associated with the risk of NB. Further, we found that this association is site specific to adrenal NB compared to non-adrenal NB. In addition, transcriptome analysis indicated that increased expression of TGFBR3L is strongly correlated with poor survival. The SNP rs11669203 located at the MYCN binding site of TGFBR3L is significantly associated with elevated risk of NB, and abnormal MYCN-regulated TGFBR3L expression may contribute to NB oncogenesis.
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Yaqiong
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Huanmin
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Surgical Oncology, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lu
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chu
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Shujing
authors.initials: S
authors.lastname: Han
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China.|Department of Head and Neck Surgery, Beijing Children's Hospital, Capital Medical University, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ni
authors.affiliation: National Center for Toxicological Research, US Food and Drug Administration, Jefferson, USA.
authors.forename: Baitang
authors.initials: B
authors.lastname: Ning
authors.affiliation: National Center for Toxicological Research, US Food and Drug Administration, Jefferson, USA. Dianke.Yu@fda.hhs.gov.
authors.forename: Dianke
authors.initials: D
authors.lastname: Yu
authors.affiliation: Beijing Key Laboratory for Pediatric Diseases of Otolaryngology, Head and Neck Surgery, Beijing Pediatric Research Institute, Beijing Children's Hospital, Capital Medical University, Beijing, China. guoyongli@bch.com.cn.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Guo
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D002681:China; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D009447:Neuroblastoma / Q000208:ethnology / Q000235:genetics*; D015513:Oncogene Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors
chemical_list: D015513:Oncogene Proteins; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C000614135:TGFBR3L protein, human
keywords: MYCN; Neuroblastoma; Single nucleotide polymorphisms; TGFBR3L