For whom the bell tolls: Susceptibility to common adult cancers in retinoblastoma survivors

In summary, the RB1 gene has been the classic paradigm for the concept of a tumor suppressor gene pathway and has provided many insights that apply broadly to the entire field of cancer biology. For many years, the intuitive notion has been that a subset of tobacco users exhibits a genetic susceptibility to developing lung cancer, but there was never evidence to directly link a specific genetic locus to this elevated risk. The RB1 gene may now serve as yet another paradigm for the concept of a genetic susceptibility locus for lung and bladder cancer among tobacco users. Accordingly, Fletcher et al. (16) conclude with the frequently stated advice that hereditary retinoblastoma survivors should avoid tobacco and chronic exposure to all other known carcinogens. However, for the large segment of the population who are not carriers of a germline RB1 mutation, it is worth remembering that many of us, similarly, will carry other genetic loci that are poised to jump-start unintended clonal proliferation in the presence of chronic carcinogen exposures. Tobacco users, therefore, should not idly wonder for whom the bell tolls.