Parental age and retinoblastoma-a retrospective study of demographic data and genetic analysis

To determine the association between the parental age gap and the absolute parental age with the risk of retinoblastoma (RB) development in an offspring.

RB individuals diagnosed between March 2013 and December 2019 in a single tertiary eye care centre were included. We recorded the demographic data, parental age and RB1 gene mutation status in the patient's tumour, blood and the parental blood. We categorised RB1 mutation inheritance as sporadic RB with somatic mutations (only present in tumour), heritable RB with de novo (present in patient's blood) and familial (present in patient and parents' blood) germline mutations. The statistical significance was confirmed by Fisher's exact/Chi-square test.

Out of 259 RB patients, 247 were included in our study. Heritable RB with de novo germline mutations was significantly less common (p value: 0.0387; 95% CI: 0.2676-0.9329) and sporadic RB with somatic mutations was more common (p value: 0.0545; 95% CI: 1.025-3.39), if the parental age gap was <10 years. There were increased odds of a heritable RB with de novo germline mutation with an increase in paternal age and this was more intensified when combined with parental age gap of more than ≥10 years. The heritable RB with de novo germline mutations significantly increased as maternal age progressed, only when it was adjusted to ≥10 years parental age gap (p value: 0.0262; 95% CI: 1.26-17.91).

An increased parental age gap and increased paternal age are independent risk factors for the development of heritable RB with de novo germline mutation.