title: Polymorphisms of insulin receptor substrate 2 are putative biomarkers for pediatric medulloblastoma: considering the genetic susceptibility and pathological diagnoses.
abstract: Molecular profiling subgrouped medulloblastoma (MB) into four subtypes featured by distinct footprints. However, germline studies on genetic susceptibility in Chinese population have not been reported. To investigate the correlation of polymorphisms involved in the AKT signaling pathway with clinicopathological parameters in pediatric MB, and their contribution to the clinical outcome, we performed a case-controlled cohort consisting of 48 patients with pediatric MB and 190 healthy controls from Han population. Significant association in rs7987237 of insulin receptor substrate 2 (IRS2) was identified as risk allele/genotype between MB patients and control group (P<0.05). The allele "C" of rs7987237 in IRS2 gene was associated with an increased risk of MB (P=0.025; OR=2.95, 95%CI 1.43-6.11) after Bonferroni correction. Among 48 patients, various genotypes of rs7987237 show significant association with pathological diagnosis and metastases risk (P<0.05). Furthermore, the survival curve of patients with genotype "CC" of rs7987237 was confirmed with better outcome (P<0.001). Combined with previous results, our study suggests that polymorphisms of IRS2 putatively participated in the development of pediatric MB development. Therefore, it may benefit the early diagnosis and indicate the prognosis of patients with MB in Han population.
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Baocheng
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Meng
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yipeng
authors.initials: Y
authors.lastname: Han
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiajia
authors.initials: J
authors.lastname: Wang
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Feili
authors.initials: F
authors.lastname: Liu
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Shengying
authors.initials: S
authors.lastname: Qin
authors.affiliation: 1Department of Pediatric Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
mesh_terms: D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007223:Infant; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics*; D008297:Male; D008527:Medulloblastoma / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D055815:Young Adult
chemical_list: C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; C491754:AKT3 protein, human; D051057:Proto-Oncogene Proteins c-akt
keywords: medulloblastoma; pathology; pediatric; prognosis; susceptibility