M E Kroll

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.

Patterns of care and survival for adolescents and young adults with acute leukaemia – a population-based study

SummaryWe report a population-based study of patterns of care and survival for people with acute leukaemia diagnosed at age 15–29 years during 1984–94 in regions of England and Wales covered by specialist leukaemia registries. There were 879 patients: 417 with acute lymphoblastic leukaemia (ALL) and 462 with acute myeloid leukaemia (AML). For ALL, actuarial survival rates were 43% at 5 years after diagnosis and 37% at 10 years. Survival improved significantly between 1984–88 and 1989–94 for those aged 15–19 at diagnosis. Patients entered in national clinical trials and those not entered had similar survival rates. Survival rates were similar at teaching and non-teaching hospitals and at hospitals treating different numbers of study patients per year. For AML, survival rates were 42% at 5 years after diagnosis and 39% at 10 years. Survival improved significantly between 1984–88 and 1989–94. Patients entered in the Medical Research Council AML10 trial had a higher survival rate than those who were in the earlier AML9 trial. Survival did not vary with category of hospital. We conclude that survival has improved for adolescents and young adults with acute leukaemia but that there is at present no evidence that centralized treatment results in a survival benefit for patients in this age group.

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.

Age at Menarche and Risks of Coronary Heart and Other Vascular Diseases in a Large UK Cohort

Background— Early menarche has been associated with increased risk of coronary heart disease (CHD), but most studies were relatively small and could not assess risk across a wide range of menarcheal ages; few have examined associations with other vascular diseases. We examined CHD, cerebrovascular disease, and hypertensive disease risks by age at menarche in a large prospective study of UK women. Methods and Results— In 1.2 million women (mean±SD age, 56±5 years) without previous heart disease, stroke, or cancer, menarcheal age was reported to be 13 years by 25%, ⩽10 years by 4%, and ≥17 years by 1%. After 11.6 years of follow-up, 73 378 women had first hospitalization for or death from CHD, 25 426 from cerebrovascular disease, and 249 426 from hypertensive disease. Using Cox regression, we calculated relative risks for each vascular outcome by single year of menarcheal age. The relationship was U-shaped for CHD. Compared with women with menarche at 13 years, the adjusted relative risk for CHD for menarche at ⩽10 years of age was 1.27 (95% confidence interval, 1.22–1.31; P<0.0001) and for menarche at ≥17 years of age was 1.23 (95% confidence interval, 1.16–1.30; P<0.0001). U-shaped relationships were also seen for cerebrovascular and hypertensive disease, although the magnitudes of these risks for early and late menarche were smaller than those for CHD. Conclusions— In this cohort, the relation of age at menarche to vascular disease risk was U shaped, with both early and late menarche being associated with increased risk. Associations were weaker for cerebrovascular and hypertensive disease than for CHD.

Population survival from childhood cancer in Britain during 1978–2005 by eras of entry to clinical trials

BACKGROUND Inclusion in clinical trials is generally viewed as best practice for most newly diagnosed childhood cancers, but the impact on population-based survival has rarely been examined. PATIENTS AND METHODS The population-based data were analysed for 25853 children (66% of all registered childhood cancers) diagnosed in Britain during 1978-2005 with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma, non-Hodgkin lymphoma, medulloblastoma, neuroblastoma, Wilms tumour, hepatoblastoma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and germ-cell tumours. The Kaplan-Meier survival curves were compared by log-rank tests. Time trends were analysed by Cox regression. Separate analyses were done for children with ALL, medulloblastoma and neuroblastoma according to clinically relevant age thresholds. RESULTS Survival increased significantly during 1978-2005 for every diagnostic category; the annual reduction in risk of death ranged from 2.7% (rhabdomyosarcoma) to 12.0% (gonadal germ-cell tumours). Survival increased steadily between trial eras for ALL (age 1-14years) and neuroblastoma (age 1-14years), but changed little since the mid-1980s for medulloblastoma (age 0-2years), osteosarcoma or Ewing sarcoma. CONCLUSIONS Changes in survival between trial eras parallel those reported by the relevant clinical trials. The increasing level of participation in trials, facilitated by the organisation of specialist care, has underpinned the substantial improvements in survival seen at the population level.BACKGROUND Inclusion in clinical trials is generally viewed as best practice for most newly diagnosed childhood cancers, but the impact on population-based survival has rarely been examined. PATIENTS AND METHODS The population-based data were analysed for 25 853 children (66% of all registered childhood cancers) diagnosed in Britain during 1978-2005 with acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), Hodgkin lymphoma, non-Hodgkin lymphoma, medulloblastoma, neuroblastoma, Wilms tumour, hepatoblastoma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma and germ-cell tumours. The Kaplan-Meier survival curves were compared by log-rank tests. Time trends were analysed by Cox regression. Separate analyses were done for children with ALL, medulloblastoma and neuroblastoma according to clinically relevant age thresholds. RESULTS Survival increased significantly during 1978-2005 for every diagnostic category; the annual reduction in risk of death ranged from 2.7% (rhabdomyosarcoma) to 12.0% (gonadal germ-cell tumours). Survival increased steadily between trial eras for ALL (age 1-14 years) and neuroblastoma (age 1-14 years), but changed little since the mid-1980s for medulloblastoma (age 0-2 years), osteosarcoma or Ewing sarcoma. CONCLUSIONS Changes in survival between trial eras parallel those reported by the relevant clinical trials. The increasing level of participation in trials, facilitated by the organisation of specialist care, has underpinned the substantial improvements in survival seen at the population level.

Retinoblastoma: Treatment and Survival in Great Britain 1963 to 2002

Aim: This paper describes the treatment and survival of 1576 children with retinoblastoma in Great Britain diagnosed 1963–2002. Methods: Survival rates were analysed according to period of diagnosis and tumour laterality. Results: Survival was calculated by calendar period of diagnosis, 1963–1982 and 1983–2002. For both unilateral and bilateral retinoblastoma, survival improved between the two periods. The survival curves for the two periods were significantly different: for unilateral retinoblastoma p<0.00001, for bilateral p<0.01. For unilateral cases, the estimated 5-year survival rates rose from 85% for those diagnosed in 1963–1967 to 97% for those diagnosed in 1998–2002. The equivalent rates for bilateral cases were 88% and 100%. Conclusion: Survival rates were already high at the start of the study period. They increased with changes in treatment regimens.

Retinoblastoma in Great Britain 1963–2002

Aim: This paper describes the epidemiology and family history status of 1601 children with retinoblastoma in Great Britain diagnosed 1963–2002 and summarises the practical consequences for diagnosis and counselling of developments in molecular genetics. Methods: Incidence rates were analysed according to year of diagnosis and tumour laterality. Cases were classified as heritable or non-heritable on the basis of laterality and family history of the disease. Results: There were 998 unilateral cases, 581 bilateral and 22 of unknown laterality. Bilateral cases tended to be diagnosed at a younger age than unilateral. All bilateral cases are regarded as heritable, and 35% had a family history of the disease. 7% of the unilateral cases had a family history and are therefore heritable. Thus, at least (41%) of our cases are heritable. This is an underestimate, since these data on family history are incomplete. For unilateral cases aged below 1 year, the reported incidence rate increased significantly (p<0.0001) by about 2.5% per year; for the age group 1–4 years, the average increase was about 0.5% per year (not significant).

Case-control studies of relation between childhood cancer and neonatal vitamin K administration

Abstract Objective: To investigate the possible link between neonatal administration of intramuscular vitamin K and childhood cancer. Design: Matched case-control study. Setting: Selected large maternity units in England and Wales. Subjects: Children with cancer born 1968-85, diagnosed 1969-86; controls matched for sex, month of birth, and hospital of birth. Main exposure measures: Neonatal administration of vitamin K, length of gestation, birth weight, type of delivery, admission to special care baby unit. Results: After exclusion of cases with missing notes or unknown hospital vitamin K policy, 597 cases and matched controls were studied. Written records on the use of vitamin K were available for only about 40% of these, and to avoid possible bias from selective recording it was assumed that the stated hospital policy was followed. The association between cancer generally and intramuscular vitamin K was of borderline significance (odds ratio 1.44, P=0.05); the association was strongest for leukaemia. There was, however, also an effect of abnormal delivery, which could explain some of the findings. Conclusions: The lack of consistency between the various studies so far published, including this one, and the low relative risks found in most of them suggest that the risk, if any, attributable to the use of vitamin K cannot be large, but the possibility that there is some risk cannot be excluded. A comparison of the predicted consequences of various policies shows that even a 10% increase would imply that prophylaxis using the commonly recommended 1 mg intramuscular dose should be restricted to babies at particularly high risk of vitamin K deficiency bleeding; alternatively a lower dose might be given to a larger proportion of those at risk. Key messages Intramuscular vitamin K given to babies is known to be effective in the prevention of vitamin K deficiency bleeding but it has been suggested that these preparations, or one of their constituents, may increase the risk of childhood cancer Most studies have not shown a significant association between childhood cancer and vitamin K but are unable to exclude the possibility that its use increases the risk of childhood cancer by up to 10% Intramuscular vitamin K has been given to “high risk” babies as part of all the various prophylaxis policies in the United Kingdom; this should continue As a small risk cannot at present be excluded it seems prudent to recommend a policy of giving intramuscular vitamin K only to those babies at particularly high risk and giving it orally to others It is essential that a record should be made of whether or not vitamin K is given and of the preparation, route of administration, and dose

Childhood cancer registration in Britain: capture-recapture estimates of completeness of ascertainment

Background:Completeness of ascertainment is a very important aspect of cancer registration. There is no recent published estimate for childhood cancer in Britain.Methods:We estimated completeness of ascertainment by the National Registry of Childhood Tumours for cancer diagnosed under age 15 years in residents of Britain during 2003–04. Stratified two-source capture-recapture was applied to notifications from general cancer registries (CRs) and specialist clinicians. Variation in notification patterns was assessed by logistic regression. Results were verified by cross-checking with Hospital Episode Statistics for leukaemia patients from England born in 1998 and diagnosed before 2005.Results:CRs notified 92–96% of registrations, and specialist clinicians 93%. Notification patterns varied slightly according to registry region, age at diagnosis, diagnostic group, socioeconomic status, and whether the patient had died. Irrespective of stratification by these factors, the overall completeness estimate was 99–100% (assuming independence of sources). Estimated completeness was at least 99% within all subgroups, except for one region (Thames 98–99%) and two small diagnostic groups (germ-cell and gonadal cancer 98–99%, melanoma and non-skin cancer 97–98%).Interpretation:The independence assumption cannot be fully justified, as both sources used records from treatment centres. With this caveat, ascertainment of recently diagnosed childhood cancer in Britain appears to be virtually complete.

Childhood leukaemia and socioeconomic status in England and Wales 1976–2005: evidence of higher incidence in relatively affluent communities persists over time

Background:Record-based studies have generally reported association of higher childhood leukaemia incidence with higher socioeconomic status (SES), but recent findings are less consistent.Methods:We examined records from the National Registry of Childhood Tumours for evidence of this association in England and Wales during 1976–2005. All eligible leukaemia registrations (N=11940) were grouped by year of diagnosis in decades centred on census years 1981, 1991 and 2001 (N=3748, 3922, 4270, respectively). Using data from the census appropriate to the decade, SES for each case was measured by the child-population-weighted quintile of the Carstairs deprivation index of the census ward containing the address at diagnosis.Results:In each decade, the age-standardised leukaemia rate in the poorest quintile was ∼90% of the rate in the most affluent. Using Poisson regression, the age-adjusted rate ratio per quintile decrease in SES was 0.96 (95% confidence interval 0.94–0.98; P<0.001 for trend) in 1976–1985, 0.97 (0.95–0.99; P=0.008) in 1986–1995 and 0.97 (0.95–0.99; P=0.009) in 1996–2005. Similar association was evident for lymphoid leukaemia, the major subgroup (N=9588 in total), but not for acute myeloid (N=1868) or other/unspecified leukaemia (N=484).Conclusion:Reported childhood leukaemia incidence in England and Wales continues to be higher in relatively affluent communities. Possible explanations include under-diagnosis of leukaemia in children from poorer communities, and/or association of higher SES with hypothesised risk factors, such as population mixing and delayed exposure to infection.