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Biomedical Research↗
Biomedical subjects
Clare Gilham
Publications and source records attributed to Clare Gilham.
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).
Adult↗
The cervical cancer epidemic that screening has prevented in the UK.
BACKGROUND: Recent reports suggest that the reduction in mortality achieved by the UK national cervical screening programme is too small to justify its financial and psychosocial costs, except perhaps in a few high-risk women. METHODS: We analysed trends in mortality before 1988, when the British national screening programme was launched, to estimate what future trends in cervical cancer mortality would have been without any screening. FINDINGS: Cervical cancer mortality in England and Wales in women younger than 35 years rose three-fold from 1967 to 1987. By 1988, incidence in this age-range was among the highest in the world despite substantial opportunistic screening. Since national screening was started in 1988, this rising trend has been reversed. INTERPRETATION: Cervical screening has prevented an epidemic that would have killed about one in 65 of all British women born since 1950 and culminated in about 6000 deaths per year in this country. However, these estimates are subject to substantial uncertainty, particularly in relation to the effects of oral contraceptives and changes in sexual behaviour. 80% or more of these deaths (up to 5000 deaths per year) are likely to be prevented by screening, which means that about 100000 (one in 80) of the 8 million British women born between 1951 and 1970 will be saved from premature death by the cervical screening programme at a cost per life saved of about pound 36000. The birth cohort trends also provide strong evidence that the death rate throughout life is substantially lower in women who were first screened when they were younger.
Adult↗