Lifetime risks of common cancers among retinoblastoma survivors.
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).
Department of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
Olivia
O
Fletcher
Douglas
D
Easton
Kristin
K
Anderson
Clare
C
Gilham
Marcelle
M
Jay
Julian
J
Peto
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000453:epidemiology / Q000235:genetics; D005260:Female; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D016012:Poisson Distribution; D019572:Retinal Neoplasms / Q000235:genetics* / Q000532:radiotherapy; D012175:Retinoblastoma / Q000235:genetics* / Q000532:radiotherapy; D018570:Risk Assessment; D012509:Sarcoma / Q000453:epidemiology / Q000235:genetics; D017741:Survivors / Q000706:statistics & numerical data; D006113:United Kingdom / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics