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; age at diagnosis; mir-34b/c; rs4938723.