G J Draper

Second primary neoplasms in patients with retinoblastoma.

In a series of 882 retinoblastoma patients, 384 known to have the genetic form of the disease and 498 others, 30 patients developed second primary neoplasms. The spectrum of these second neoplasms is discussed in relation to the forms of treatment used for the retinoblastoma. Cumulative incidence rates of second tumours in the whole series are 2.0% at 12 years after diagnosis and 4.2% after 18 years. For patients with the genetic form of retinoblastoma the cumulative incidence rate after 18 years is 8.4% for all second neoplasms and 6.0% for osteosarcomas alone. The inherent risk among survivors from genetic retinoblastoma of developing an osteosarcoma, excluding all possible effects of treatment, is estimated to be 2.2% after 18 years. Within the field of radiation treatment the cumulative incidence rate for all second neoplasms after 18 years is 6.6% and for osteosarcomas alone 3.7%. There is some evidence that patients with genetic retinoblastoma are particularly sensitive to the carcinogenic effects of radiation. The results also suggest that the use of cyclophosphamide may increase the risk of second primary neoplasms in patients with genetic retinoblastoma. The incidence rates of second primary neoplasms in retinoblastoma survivors reported here are lower than those quoted for previously published series. Evidence from this and other papers strongly suggests an association between retinoblastoma and malignant melanoma.

Childhood cancer in relation to distance from high voltage power lines in England and Wales: a case-control study

Abstract Objective To determine whether there is an association between distance of home address at birth from high voltage power lines and the incidence of leukaemia and other cancers in children in England and Wales. Design Case-control study. Setting Cancer registry and National Grid records. Subjects Records of 29 081 children with cancer, including 9700 with leukaemia. Children were aged 0-14 years and born in England and Wales, 1962-95. Controls were individually matched for sex, approximate date of birth, and birth registration district. No active participation was required. Main outcome measures Distance from home address at birth to the nearest high voltage overhead power line in existence at the time. Results Compared with those who lived > 600 m from a line at birth, children who lived within 200 m had a relative risk of leukaemia of 1.69 (95% confidence interval 1.13 to 2.53); those born between 200 and 600 m had a relative risk of 1.23 (1.02 to 1.49). There was a significant (P < 0.01) trend in risk in relation to the reciprocal of distance from the line. No excess risk in relation to proximity to lines was found for other childhood cancers. Conclusions There is an association between childhood leukaemia and proximity of home address at birth to high voltage power lines, and the apparent risk extends to a greater distance than would have been expected from previous studies. About 4% of children in England and Wales live within 600 m of high voltage lines at birth. If the association is causal, about 1% of childhood leukaemia in England and Wales would be attributable to these lines, though this estimate has considerable statistical uncertainty. There is no accepted biological mechanism to explain the epidemiological results; indeed, the relation may be due to chance or confounding.

Retinoblastoma in Great Britain 1969-80: incidence, treatment, and survival.

Patients with retinoblastoma diagnosed from 1969 to 1980 have been followed up for periods of up to 17 years. Data from a previous study of patients diagnosed from 1962 to 1968 have been included for analysis of incidence and second primary tumours, and for study of trends in treatment. The registration rate in Britain (which may be about 10% less than the true incidence) is about one in 23,000 live births, approximately 40% of cases being known to be genetic. There is no apparent trend in incidence during the period covered by these two studies. The three-year survival rate in 88%. Patients with bilateral tumours have a better survival rate than those with unilateral tumours for the first few years, but their long-term survival rate is worse because of later deaths from ectopic intracranial retinoblastoma or second primary neoplasms. Older children tend to have a worse prognosis, which is related to the fact that their tumours are diagnosed at a more advanced stage. There is a significantly higher survival rate for boys than for girls; this is partly accounted for by difference in age and stage at diagnosis between the sexes. Children referred to units specialising in the treatment of retinoblastoma have a higher three-year survival rate than those treated at other hospitals. Comparing methods of treatment between the periods 1962-8 and 1969-80, we find there has been a trend towards more conservative treatment. The use of chemotherapy is now usually reserved for recurrences and metastases and for palliative treatment in terminal retinoblastoma.

The inter-regional epidemiological study of childhood cancer (IRESCC): a case control study of aetiological factors in leukaemia and lymphoma

The inter-regional epidemiological study of childhood cancer analysed data on 234 children diagnosed with leukaemia or lymphoma and 468 controls matched for age and sex. A wide range of potential risk factors was examined, including prenatal exposure to x rays, maternal drug ingestion and smoking, childs medical history, and parental medical conditions and occupation. Calculations were completed for leukaemia or lymphoma and diagnostic subgroups, as defined by laboratory confirmed cell type. In utero exposure to narcotic analgesics was weakly associated with leukaemia or lymphoma but no other antenatal factors gave significant risks. New associations were identified for skin diseases in both parents and congenital abnormalities in the mothers of children with leukaemia. For past medical conditions in the child, viral disease occurring under 6 months of age increased the risk for acute lymphoblastic leukaemia. Fewer children in the leukaemia or lymphoma group had been immunised compared with the control groups. Case children diagnosed over the age of 9 years were more likely than controls to have had four or more previous episodes of illness. Overall, these results indicate that prenatal factors may be less important than postnatal or genetic influences in the development of leukaemia or lymphoma in children.

Occurrence of childhood cancers among sibs and estimation of familial risks.

An analysis which includes the majority of the cases of childhood cancer occurring in Britain over a period of about 20 years suggests that there is a small familial element in the aetiology of these diseases; aggregations within sibships were observed more frequently than would be expected by chance. Possible explanations of these findings are considered. Some, perhaps many, of the cases within such sibships may be due to associations between malignant disease and various genetically determined conditions at a suclinical level or in the heterozygous state. Alternatively, the observed familial aggregations may be attributable to the fact that sibs share a common environment. Childhood cancer in twins is discussed and findings compared with those from the United States. Attention is drawn to a number of interesting combinations of tumours in sibs, particularly brain tumours and bone cancers. The implications of the findings for genetic counselling are discussed; it is emphasized that, though there appears to be an increased risk that sibs of children with malignant disease will also be affected by such diseases, this amounts overall only to a doubling of the general population risk. Whether or not the explanation is a genetic one, the actual magnitude of the risk for such sibs is only about 1 in 300.

Retinoblastoma: A Study of Natural History and Prognosis of 268 Cases

The natural history and prognosis of retinoblastoma were analysed using data relating to the 268 cases registered during 1962-8 in England, Scotland, and Wales. The children were followed up for a minimum of four years; the proportion surviving for four years was 86%. The most important factors affecting survival rate were the stage of the tumour at diagnosis and the hospital of treatment. Of children surviving for three years after treatment only three died during the subsequent period of follow-up, which varied from one to seven years. Among children with retinoblastoma treated between 1949 and 1968 nine died between seven and 13 years later of other cancers: seven from osteosarcomas, one from angiosarcoma, and one from fibrosarcoma.

Distribution of childhood leukaemias and non-Hodgkin's lymphomas near nuclear installations in England and Wales

Abstract Objective : To examine the relation between the risk of childhood leukaemia and non-Hodgkins lymphoma and proximity of residence to nuclear installations in England and Wales. Design : Observed and expected numbers of cases were calculated and analysed by standard methods based on ratios of observed to expected counts and by a new statistical test, the linear risk score test, based on ranks and designed to be sensitive to excess incidence in close proximity to a putative source of risk. Setting : Electoral wards within 25 km of 23 nuclear installations and six control sites that had been investigated for suitability for generating stations but never used. Subjects : Children below age 15 in England and Wales, 1966-87. Main outcome measure - Registration of any leukaemia or non-Hodgkins lymphoma. Results : In none of the 25 km circles around the installations was the incidence ratio significantly greater than 1.0. The only significant results for the linear risk score test were for Sellafield (P=0.00002) and Burghfield (P=0.031). The circles for Aldermaston and Burghfield overlap; the incidence ratio was 1.10 in each. One of the control sites gave a significant linear risk score test result (P=0.020). All the tests carried out were one sided with P values estimated by simulation. Conclusion : There is no evidence of a general increase of childhood leukaemia or non-Hodgkins lymphoma around nuclear installations. Apart from Sellafield, the evidence for distance related risk is very weak.

Cancer in Cumbria and in the vicinity of the Sellafield nuclear installation, 1963-90.

OBJECTIVE--To reappraise the epidemiological findings reported by the Black Advisory Group concerning a possible excess of malignant disease, particularly of childhood acute lymphoid leukaemia and non-Hodgkin lymphomas, in the vicinity of the Sellafield nuclear installation, and to determine whether any excess of malignant disease had occurred among people aged 0-24 years in the area in the years after the Black report--that is, from 1984 to 1990. DESIGN--Calculation of incidence of cancer using data from population based cancer registries and special surveys. SETTING--England and Wales; county of Cumbria; county districts Allerdale and Copeland within Cumbria; Seascale ward within Copeland. SUBJECTS--All residents under the age of 75 years in the above areas, but with particular reference to those aged 0-24 years. MAIN OUTCOME MEASURES--Numbers of cases and incidence particularly of lymphoid leukaemia and non-Hodgkin lymphomas in those aged 0-24 years, but including other cancers and age groups. RESULTS--Previous reports of an increased incidence of cancer, especially of leukaemia, among those aged 0-24 years in Seascale during the period up to and including 1983 are confirmed. During 1984-90 there was an excess of total cancer among those aged 0-24 years. This was based on four cases including two cases of non-Hodgkin lymphoma but none of leukaemia. There was an increased, but nonsignificant, incidence of other cancers, based on two cases (one pinealoma and one Hodgkins disease) occurring among those aged 15-24 years during 1984-90. This was not observed in the younger age group or in previous years. For the immediately surrounding area--that is, the county districts of Allerdale and Copeland excluding Seascale and in the remainder of Cumbria--there was no evidence of an increased incidence of cancer among those aged 0-24 years in either period. CONCLUSIONS--During 1963-83 and 1984-90 the incidence of malignant disease, particularly lymphoid leukaemia and non-Hodgkin lymphomas, in young people aged 0-24 in Seascale was higher than would be expected on the basis of either national rates or those for the surrounding areas. Although this increased risk is unlikely to be due to chance, the reasons for it are still unknown.

Childhood cancer and magnetic fields from high-voltage power lines in England and Wales: a case–control study

Background:Epidemiological evidence suggests that chronic low-intensity extremely-low-frequency magnetic-field exposure is associated with increased risk of childhood leukaemia; it is not certain the association is causal.Methods:We report a national case–control study relating childhood cancer risk to the average magnetic field from high-voltage overhead power lines at the childs home address at birth during the year of birth, estimated using National Grid records. From the National Registry of Childhood Tumours, we obtained records of 28 968 children born in England and Wales during 1962–1995 and diagnosed in Britain under age 15. We selected controls from birth registers, matching individually by sex, period of birth, and birth registration district. No participation by cases or controls was required.Results:The estimated relative risk for each 0.2 μT increase in magnetic field was 1.14 (95% confidence interval 0.57 to 2.32) for leukaemia, 0.80 (0.43–1.51) for CNS/brain tumours, and 1.34 (0.84–2.15) for other cancers.Conclusion:Although not statistically significant, the estimate for childhood leukaemia resembles results of comparable studies. Assuming causality, the estimated attributable risk is below one case per year. Magnetic-field exposure during the year of birth is unlikely to be the whole cause of the association with distance from overhead power lines that we previously reported.

Cancer incidence in children conceived with assisted reproduction technology

lacrimal gland; and -defensin-2 message in cornea and conjunctiva but not lacrimal gland. -defensins 5 and 6 were absent. Purified or recombinant defensins may be useful treatments for eye infections because defensins have a broad spectrum of activity, are chemotactic for monocytes, accelerate wound healing, and may be non-antigenic, whereas most antibiotics have a comparatively limited spectrum of activity, interfere with healing due to ocular surface toxicity, and may produce allergic reactions. Defensins may be effective in the treatment of established ocular-surface infections or prevention of keratitis in eyes at particular risk, such as dry-eye states, contact-lens wearers, critically ill or comatose patients, or after ophthalmic surgery. Factors that control the production of defensins are unknown and it is likely that some of the risk factors mentioned above are associated with down-regulation of production.