Risk Factors for the Incidence of Second Cancers in Survivors of Retinoblastoma With a Family History

Abstract

TO THE EDITOR: Kleinerman et al recently published an article concerning variations in second cancer risk by family history of retinoblastoma among long-term survivors of retinoblastoma. They concluded that retinoblastoma survivors with bilateral disease and an inherited germline mutation are at slightly higher risk of a second cancer (in particular, melanoma) compared with those with a de novo germline mutation, perhaps because of shared genetic alterations. As Kleinerman et al stated in the Patients and Methods section of their article, genetic testing data were not available for all of the survivors in their study; therefore, they used laterality and family history as asurrogateforthepresenceofaninheritedordenovogermlinemutation. It is possible that between 6% and 10% of survivors of retinoblastoma with a de novo mutation are in fact mosaic for the mutation. Kaye and Harbour reported that in survivors of sporadic hereditary retinoblastoma with the mosaic form, the risk of a second cancer may be elevated to a lesser extent, given that not all cells carry the RB1 mutation and thus not all tissues are at risk for a second cancer. This could explain the difference in risk of second cancers between sporadic and familial retinoblastoma as reported by Kleinerman et al, because for the patients with familial retinoblastoma, mosaicism is excluded and all tissues are at risk for second cancers. Kleinerman et al are to be complimented for their interesting study. However, we believe that the slightly higher risk of a second cancer in survivors of bilateral retinoblastoma and an inherited germline mutation (47%) compared with those with a de novo germline mutation (38%) could also be explained by mosaicism.