Non-Ocular Cancers in Parents of Patients Diagnosed with Retinoblastoma in Britain 1949 to 1987

Background: Mutations in the retinoblastoma gene (RB1) are associated with risks of both retinoblastoma and other cancers. Parents of children with retinoblastoma can be categorised according to their likelihood of carrying a germline RB1 mutation. Some categories of such parents may have an increased risk of cancer. Methods: A cohort of 1180 parents of children with retinoblastoma were categorised according to the likelihood that they carried an RB1 mutation and followed up for cancer through national records. We calculated Standardised Incidence Ratios (SIRs) for all non-ocular cancers combined and for individual diagnostic groups, with expected numbers derived from national cancer registration rates. Finally, we pooled the all-cancers results from the present study with those from an earlier study of largely the same cohort with non-overlapping follow-up. Results: In total, 183 non-ocular cancers were identified among the parents. Parents who themselves had retinoblastoma had a significantly higher risk of non-ocular cancer than the general population: for fathers, the SIR was 3.56 (95% confidence interval (CI) 1.84–6.22); for mothers, it was 3.25 (1.49–6.18). For the very small group of parents known to be carrying a germline RB1 mutation but not affected by retinoblastoma, there was a lower and non-significant increase in risk (SIR = 1.9). Parents categorised as either possible carriers or probable non-carriers had similar observed risks to the general population. When the all-cancers results were pooled with those from an earlier study of very largely the same cohort with non-overlapping follow-up, the estimated lifetime SIR for non-ocular cancer among mutation-carrier parents after the birth of their affected child was 4.32 (95% CI 3.06–5.93). Conclusions: Our results confirm that parents who themselves had retinoblastoma have an increased risk of subsequent cancers, and parents who are not mutation carriers have a risk similar to the general population.