Affiliations: [a] Genetics Department, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil | [b] Birth Defects Epidemiology Laboratory, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil | [c] Genetics Division, Genetics Counseling Program, Instituto Nacional de Cancer, Rio de Janeiro, RJ, Brazil | [d] Genetics and Molecular Department, Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Correspondence:
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Corresponding author: Fernando R. Vargas, Birth Defects Epidemiology Laboratory, IOC, Fiocruz, Av Brasil 4365, 21040-360 Rio de Janeiro, RJ, Brazil. Tel./Fax: +55 21 38658141; E-mail:fernando.vargas@ioc.fiocruz.br
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.
Keywords: Retinoblastoma, mir-34b/c, rs4938723, age at diagnosis
