title: A polymorphism in mir-34b/c as a potential biomarker for early onset of hereditary retinoblastoma.
abstract: BACKGROUND
  Retinoblastoma (RB) is a malignant pediatric tumor and, mainly because of late diagnosis, most patients undergo enucleation. The tumor almost always initiates by two inactivation events at the RB1 gene. Single nucleotide polymorphisms (SNPs) in p53 pathway have been found to represent genetic modifiers of RB.
  
  
  OBJECTIVE
  To investigate whether a SNP (rs4938723T > C) in mir-34b/c gene, a key effector of p53, could influence RB risk and patients' age of onset.
  
  
  METHODS
  mir-34b/c rs4938723T > C was sequenced in 130 RB patients and in 105 control individuals. Statistical analysis consisted of χ 2 tests or Fisher's exact, odds ratios (ORs) and Mann-Whitney test.
  
  
  RESULTS
  The presence of the C allele did not change the risk for retinoblastoma. However, in hereditary RB patients, the mean age at diagnosis is much lower (1.4 ± 1.4 months) among CC carriers than when it is compared to TT genotype (13.8 ± 6.4, p = 0.001). Besides, hereditary RB patients with CC genotype are around 4 times more likely to present retinoblastoma under the age of 3 months (OR = 4.44; IC: 2.50-7.90; p = 0.002).
  
  
  CONCLUSIONS
  The C allele together with a germ-line RB1 gene mutation may speed retinoblastoma onset which suggests that mir-34b/c rs4938723T > C may represent a candidate biomarker for hereditary RB.
authors.affiliation: Genetics Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|Birth Defects Epidemiology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.
authors.forename: Ivna N S R
authors.initials: IN
authors.lastname: Carvalho
authors.affiliation: Genetics Division, Genetics Counseling Program, Instituto Nacional de Cancer, Rio de Janeiro, RJ, Brazil.
authors.forename: Adriana H O
authors.initials: AH
authors.lastname: Reis
authors.affiliation: Genetics Division, Genetics Counseling Program, Instituto Nacional de Cancer, Rio de Janeiro, RJ, Brazil.
authors.forename: Anna C E
authors.initials: AC
authors.lastname: Dos Santos
authors.affiliation: Genetics Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.|Birth Defects Epidemiology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil.|Genetics and Molecular Department, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Vargas
mesh_terms: D017668:Age of Onset; D000483:Alleles; D014408:Biomarkers, Tumor; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D016161:Genes, Retinoblastoma; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012175:Retinoblastoma / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs
keywords: Retinoblastoma; age at diagnosis; mir-34b/c; rs4938723