© 2004 by Oxford University Press
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
© 2004 Oxford University Press
ARTICLE |
Lifetime Risks of Common Cancers Among Retinoblastoma Survivors
Affiliations of authors: Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK (OF, JP); Cancer Research UK Genetic Epidemiology Unit, Department of Public Health, University of Cambridge, Cambridge, UK (DE); Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, MN (KA); Cancer Research UK Epidemiology and Genetics Unit, The Institute of Cancer Research, Surrey, UK (CG, JP); Institute of Ophthalmology, London (MJ).
Correspondence to: Professor Julian Peto, Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, Keppel St., London, WC13 7HT, UK (e-mail: julian.peto{at}icr.ac.uk)
Background: Compared with the general population, carriers of germline mutations in RB1 who survive retinoblastoma (i.e., hereditary retinoblastoma survivors) are at increased risk of early-onset second cancers, particularly sarcomas, brain tumors, and melanoma. However, their risks for the epithelial cancers that commonly occur after age 50 years are not known. Methods: We used hospital records to identify British retinoblastoma survivors born between 1873 and 1950, a period when few British retinoblastoma patients received high-dose radiotherapy. Cancers and deaths were identified by linkage with national registration records. All statistical tests were two-sided. Results: We could trace the cancer histories of 144 survivors of hereditary retinoblastoma. From age 25 to age 84, there were 58 subsequent cancers, for a cumulative cancer incidence of 68.8% (95% confidence interval [CI] = 48.0% to 87.4%) and a cumulative cancer mortality of 56.3% (95% CI = 40.5% to 73.3%). Only eight of the 58 cancers were of bone or soft tissue, in marked contrast to findings from contemporary studies of American patients treated with external beam radiotherapy, among whom most second tumors are sarcomas. Compared with the general population, hereditary retinoblastoma survivors had higher mortality from lung cancer (standardized mortality ratio [SMR] = 7.01, 95% CI = 3.83 to 11.76), bladder cancer (SMR = 26.31, 95% CI = 8.54 to 61.41), and all other epithelial cancers combined (SMR = 3.29, 95% CI = 1.64 to 5.89). The overall standardized mortality ratio for epithelial cancer was inversely proportional to the approximate square of age (exponent of age = -2.1, 95% CI = -3.6 to -0.7), declining from 11.32 (95% CI = 4.15 to 24.64) at age 25–44 to 2.83 (95% CI = 1.04 to 6.16) at age 65–84. Conclusions: Survivors of hereditary retinoblastoma who are not exposed to high-dose radiotherapy have a high lifetime risk of developing a late-onset epithelial cancer. Most of the excess cancer risks in hereditary retinoblastoma survivors might be preventable by limiting exposures to DNA damaging agents (radiotherapy, tobacco, and UV light).
CiteULike 
Connotea 
Del.icio.us What's this?
Editorial about this Article
- For Whom the Bell Tolls: Susceptibility to Common Adult Cancers in Retinoblastoma Survivors
- Frederic J. Kaye and J. William Harbour
J Natl Cancer Inst 2004 96: 342-343.[Extract] [Full Text] [PDF]
This article has been cited by other articles:
|
|
 |
|
  S. Gratias, H. Rieder, R. Ullmann, L. Klein-Hitpass, S. Schneider, R. Boloni, M. Kappler, and D. R. Lohmann Allelic Loss in a Minimal Region on Chromosome 16q24 Is Associated with Vitreous Seeding of Retinoblastoma Cancer Res., January 1, 2007; 67(1): 408 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Chin, L. A. Garraway, and D. E. Fisher Malignant melanoma: genetics and therapeutics in the genomic era. Genes & Dev., August 15, 2006; 20(16): 2149 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. A. Kiemeney, R. P. Kuiper, R. Pfundt, S. van Reijmersdal, M. P. Schoenberg, K. K. Aben, M. F. Niermeijer, J. A. Witjes, and E. F.P.M. Schoenmakers No Evidence For Large-scale Germline Genomic Aberrations in Hereditary Bladder Cancer Patients with High-Resolution Array-Based Comparative Genomic Hybridization Cancer Epidemiol. Biomarkers Prev., January 1, 2006; 15(1): 180 - 183. [Full Text] [PDF]
|
|
|
|
 |
|
 D. H. Abramson Retinoblastoma in the 20th Century: Past Success and Future Challenges The Weisenfeld Lecture Invest. Ophthalmol. Vis. Sci., August 1, 2005; 46(8): 2684 - 2691. [Full Text] [PDF]
|
|
|
|
 |
|
 R. A. Kleinerman, M. A. Tucker, R. E. Tarone, D. H. Abramson, J. M. Seddon, M. Stovall, F. P. Li, and J. F. Fraumeni Jr Risk of New Cancers After Radiotherapy in Long-Term Survivors of Retinoblastoma: An Extended Follow-Up J. Clin. Oncol., April 1, 2005; 23(10): 2272 - 2279. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. E. Bosco and E. S. Knudsen Differential role of RB in response to UV and IR damage Nucleic Acids Res., March 14, 2005; 33(5): 1581 - 1592. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Garber and K. Offit Hereditary Cancer Predisposition Syndromes J. Clin. Oncol., January 10, 2005; 23(2): 276 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. J. Kaye and J. W. Harbour For Whom the Bell Tolls: Susceptibility to Common Adult Cancers in Retinoblastoma Survivors J Natl Cancer Inst, March 3, 2004; 96(5): 342 - 343. [Full Text] [PDF]
|
|