Modelling the bimodal distribution of indoor gamma-ray dose-rates in Great Britain.

Gamma radiation from naturally occurring sources (including directly ionizing cosmic-rays) is a major component of background radiation. An understanding of the magnitude and variation of doses from these sources is important, and the ability to predict them is required for epidemiological studies. In the present paper, indoor measurements of naturally occurring gamma-rays at representative locations in Great Britain are summarized. It is shown that, although the individual measurement data appear unimodal, the distribution of gamma-ray dose-rates when averaged over relatively small areas, which probably better represents the underlying distribution with inter-house variation reduced, appears bimodal. The dose-rate distributions predicted by three empirical and geostatistical models are also bimodal and compatible with the distributions of the areally averaged dose-rates. The distribution of indoor gamma-ray dose-rates in the UK is compared with those in other countries, which also tend to appear bimodal (or possibly multimodal). The variation of indoor gamma-ray dose-rates with geology, socio-economic status of the area, building type, and period of construction are explored. The factors affecting indoor dose-rates from background gamma radiation are complex and frequently intertwined, but geology, period of construction, and socio-economic status are influential; the first is potentially most influential, perhaps, because it can be used as a general proxy for local building materials. Various statistical models are tested for predicting indoor gamma-ray dose-rates at unmeasured locations. Significant improvements over previous modelling are reported. The dose-rate estimates generated by these models reflect the imputed underlying distribution of dose-rates and provide acceptable predictions at geographical locations without measurements.

Levels of naturally occurring gamma radiation measured in British homes and their prediction in particular residences.

Gamma radiation from natural sources (including directly ionising cosmic rays) is an important component of background radiation. In the present paper, indoor measurements of naturally occurring gamma rays that were undertaken as part of the UK Childhood Cancer Study are summarised, and it is shown that these are broadly compatible with an earlier UK National Survey. The distribution of indoor gamma-ray dose rates in Great Britain is approximately normal with mean 96 nGy/h and standard deviation 23 nGy/h. Directly ionising cosmic rays contribute about one-third of the total. The expanded dataset allows a more detailed description than previously of indoor gamma-ray exposures and in particular their geographical variation. Various strategies for predicting indoor natural background gamma-ray dose rates were explored. In the first of these, a geostatistical model was fitted, which assumes an underlying geologically determined spatial variation, superimposed on which is a Gaussian stochastic process with Matérn correlation structure that models the observed tendency of dose rates in neighbouring houses to correlate. In the second approach, a number of dose-rate interpolation measures were first derived, based on averages over geologically or administratively defined areas or using distance-weighted averages of measurements at nearest-neighbour points. Linear regression was then used to derive an optimal linear combination of these interpolation measures. The predictive performances of the two models were compared via cross-validation, using a randomly selected 70 % of the data to fit the models and the remaining 30 % to test them. The mean square error (MSE) of the linear-regression model was lower than that of the Gaussian-Matérn model (MSE 378 and 411, respectively). The predictive performance of the two candidate models was also evaluated via simulation; the OLS model performs significantly better than the Gaussian-Matérn model.

Epidemiological study of power lines and childhood cancer in the UK: further analyses.

We report further analyses from an epidemiological study of childhood cancer and residence at birth near high-voltage power lines in the UK. These results suggest that the elevated risks for childhood leukaemia that we previously found for overhead power lines may be higher for older age at diagnosis and for myeloid rather than lymphoid leukaemia. There are differences across regions of birth but not forming any obvious pattern. Our results suggest the decline in risk we previously reported from the 1960s to the 2000s is linked to calendar year of birth or of cancer occurrence rather than the age of the power lines concerned. Finally, we update our previous analysis of magnetic fields to include later subjects.

Magnetic fields and childhood cancer: an epidemiological investigation of the effects of high-voltage underground cables.

Epidemiological evidence of increased risks for childhood leukaemia from magnetic fields has implicated, as one source of such fields, high-voltage overhead lines. Magnetic fields are not the only factor that varies in their vicinity, complicating interpretation of any associations. Underground cables (UGCs), however, produce magnetic fields but have no other discernible effects in their vicinity. We report here the largest ever epidemiological study of high voltage UGCs, based on 52,525 cases occurring from 1962-2008, with matched birth controls. We calculated the distance of the mother's address at child's birth to the closest 275 or 400 kV ac or high-voltage dc UGC in England and Wales and the resulting magnetic fields. Few people are exposed to magnetic fields from UGCs limiting the statistical power. We found no indications of an association of risk with distance or of trend in risk with increasing magnetic field for leukaemia, and no convincing pattern of risks for any other cancer. Trend estimates for leukaemia as shown by the odds ratio (and 95% confidence interval) per unit increase in exposure were: reciprocal of distance 0.99 (0.95-1.03), magnetic field 1.01 (0.76-1.33). The absence of risk detected in relation to UGCs tends to add to the argument that any risks from overhead lines may not be caused by magnetic fields.

Residential mobility and associated factors in relation to the assessment of exposure to naturally occurring radiation in studies of childhood cancer.

Migration, that is the study subjects moving from one residential address to another, is a complication for epidemiological studies where exposures to the agent of interest depend on place of residence [corrected]. In this paper we explore migration in cases from a large British case-control study of childhood cancer and natural background radiation. We find that 44% of cases had not moved house between birth and diagnosis, and about two-thirds were living within 2 km of their residence at birth. The estimated dose at the diagnosis address was strongly correlated with that at the birth address, suggesting that use of just the birth address in this case-control study does not lead to serious bias in risk estimates. We also review other individual-based studies of naturally occurring radiation, with particular emphasis on those from Great Britain. Interview-based case-control and cohort studies can potentially establish full residential histories for study subjects and make direct measurements of radiation levels in the dwellings in question. However, in practice, because of study size and difficulties in obtaining adequate response rates, interview-based studies generally do not use full residential histories, and a substantial proportion of dose estimates often derive from models rather than direct measurements. More seriously, problems of incomplete response may lead to bias, not just to loss of power. Record-based case-control studies, which do not require direct contact with study subjects, avoid such problems, but at the expense of having only model-based exposure estimates that use databases of measurements.

Residential distance at birth from overhead high-voltage powerlines: childhood cancer risk in Britain 1962-2008.

BACKGROUND: We extend our previous study of childhood leukaemia and proximity to high-voltage powerlines by including more recent data and cases and controls from Scotland, by considering 132-kV powerlines as well as 275 and 400 kV and by looking at greater distances from the powerlines. METHODS: Case-control study using 53,515 children from the National Registry of Childhood Tumours 1962-2008, matched controls, and calculated distances of mother's address at child's birth to powerlines at 132, 275, and 400 kV in England, Wales and Scotland. RESULTS: Our previous finding of an excess risk for leukaemia at distances out to 600 m declines over time. Relative risk and 95% confidence interval for leukaemia, 0-199 m compared with>1000 m, all voltages: 1960s 4.50 (0.97-20.83), 2000s 0.71 (0.49-1.03), aggregate over whole period 1.12 (0.90-1.38). Increased risk, albeit less strong, may also be present for 132-kV lines. Increased risk does not extend beyond 600 m for lines of any voltage. CONCLUSIONS: A risk declining over time is unlikely to arise from any physical effect of the powerlines and is more likely to be the result of changing population characteristics among those living near powerlines.

Updated investigations of cancer excesses in individuals born or resident in the vicinity of Sellafield and Dounreay.

BACKGROUND: Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analyses relating to areas close to these nuclear installations by considering data from an additional 16 years of follow-up. METHODS: Cross-sectional analyses compared cancer incidence rates for 1963-2006 among those aged 0-24 years at diagnosis living in geographically specified areas around either Sellafield or Dounreay with general population rates. Cancer incidence for the period 1971-2006 among the cohort of Cumbrian births between 1950 and 2006 was compared to national incidence for 1971-2006 using person-years analysis. Cancer among those born in the postcode sector closest to Dounreay was compared with that among those born in the three adjoining postcode sectors. Analyses considered both cancer overall and ICD-O-3 defined diagnostic subgroups including leukaemia, central nervous system tumours and other malignancies. RESULTS: Apart from previously reported raised risks, no new significantly increased risks for cancer overall or any diagnostic subgroup were found among children or teenagers and young adults living around either nuclear installation. Individuals born close to the installations from 1950 to 2006 were not shown to be at any increased risk of cancer during the period 1971 to date. CONCLUSIONS: Analysis of recent data suggests that children, teenagers and young adults currently living close to Sellafield and Dounreay are not at an increased risk of developing cancer. Equally, there is no evidence of any increased cancer risk later in life among those resident in these areas at birth.

Relative accuracy of grid references derived from postcode and address in UK epidemiological studies of overhead power lines.

In the UK, the location of an address, necessary for calculating the distance to overhead power lines in epidemiological studies, is available from different sources. We assess the accuracy of each. The grid reference specific to each address, provided by the Ordnance Survey product Address-Point, is generally accurate to a few metres, which will usually be sufficient for calculating magnetic fields from the power lines. The grid reference derived from the postcode rather than the individual address is generally accurate to tens of metres, and may be acceptable for assessing effects that vary in the general proximity of the power line, but is probably not acceptable for assessing magnetic-field effects.

Childhood cancer and exposure to corona ions from power lines: an epidemiological test.

We previously reported an association between childhood leukaemia in Britain and proximity of the child's address at birth to high-voltage power lines that declines from the 1960s to the 2000s. We test here whether a 'corona-ion hypothesis' could explain these results. This hypothesis proposes that corona ions, atmospheric ions produced by power lines and blown away from them by the wind, increase the retention of airborne pollutants in the airways when breathed in and hence cause disease. We develop an improved model for calculating exposure to corona ions, using data on winds from meteorological stations and considering the whole length of power line within 600 m of each subject's address. Corona-ion exposure is highly correlated with proximity to power lines, and hence the results parallel the elevations in leukaemia risk seen with distance analyses. But our model explains the observed pattern of leukaemia rates around power lines less well than straightforward distance measurements, and ecological considerations also argue against the hypothesis. This does not disprove the corona-ion hypothesis as the explanation for our previous results, but nor does it provide support for it, or, by extension, any other hypothesis dependent on wind direction.

Second and subsequent tumours among 1927 retinoblastoma patients diagnosed in Britain 1951-2004.

BACKGROUND: Retinoblastoma is an eye tumour of childhood that occurs in heritable and non-heritable forms. In the heritable form, there is a predisposition to the development of non-ocular subsequent primary tumours (SPTs). METHODS: This study included 1927 retinoblastoma patients diagnosed in Britain from 1951 to 2004. Ascertainment was through the (UK) National Registry of Childhood Tumours; cases were followed-up for the occurrence of SPTs. Standardised incidence ratios (SIRs) were calculated. RESULTS: We identified 169 SPTs in 152 patients. The SIR analysis included 145 SPTs with cancer registrations from the years 1971 to 2009. These tumours occurred in 132 patients: 112 of the 781 heritable and 20 of the 1075 (presumed) non-heritable cases under surveillance at the start of this period developed at least one registered SPT. The SIRs for all tumours combined were 13.7 (95% confidence interval 11.3-16.5) in heritable cases and 1.5 (0.9-2.3) in non-heritable cases. The main types of SPT in the heritable cases were leiomyosarcoma, (31 cases; SIR 1018.7 (692.2-1446.0)), osteosarcoma (26 cases; SIR 444.6 (290.4-651.4)), and skin melanoma (12 cases; SIR 18.6 (9.6-32.4)). CONCLUSION: The risk of SPTs in heritable retinoblastoma is extremely high. This has important implications for the clinical follow-up and counselling of survivors and their families.

Case-control study of paternal occupation and social class with risk of childhood central nervous system tumours in Great Britain, 1962-2006.

BACKGROUND: Paternal occupational exposures have been proposed as a risk factor for childhood central nervous system (CNS) tumours. This study investigates possible associations between paternal occupational exposure and childhood CNS tumours in Great Britain. METHODS: The National Registry of Childhood Tumours provided all cases of childhood CNS tumours born and diagnosed in Great Britain from 1962 to 2006. Controls without cancer were matched on sex, period of birth and birth registration sub-district. Fathers' occupations were assigned to one or more of 33 exposure groups. A measure of social class was also derived from father's occupation at the time of the child's birth. RESULTS: Of 11 119 cases of CNS tumours, 5 722 (51%) were astrocytomas or other gliomas, 2 286 (21%) were embryonal and 985 (9%) were ependymomas. There was an increased risk for CNS tumours overall with exposure to animals, odds ratio (OR) 1.40 (95% confidence intervals (CIs) 1.01, 1.94) and, after adjustment for occupational social class (OSC), with exposure to lead, OR 1.18 (1.01, 1.39). Exposure to metal-working oil mists was associated with reduced risk of CNS tumours, both before and after adjustment for OSC, OR 0.87 (0.75, 0.99).Risk of ependymomas was raised for exposure to solvents, OR 1.73 (1.02,2.92). For astrocytomas and other gliomas, risk was raised with high social contact, although this was only statistically significant before adjustment for OSC, OR 1.15 (1.01,1.31). Exposure to paints and metals appeared to reduce the risk of astrocytomas and embryonal tumours, respectively. However, as these results were the result of a number of statistical tests, it is possible they were generated by chance.Higher social class was a risk factor for all CNS tumours, OR 0.97 (0.95, 0.99). This was driven by increased risk for higher social classes within the major subtype astrocytoma, OR 0.95 (0.91, 0.98). CONCLUSION: Our results provide little evidence that paternal occupation is a significant risk factor for childhood CNS tumours, either overall or for specific subtypes. However, these analyses suggest that OSC of the father may be associated with risk of some childhood CNS cancers.

Case-control study of paternal occupation and childhood leukaemia in Great Britain, 1962-2006.

BACKGROUND: Paternal occupational exposures have been proposed as a risk factor for childhood leukaemia. This study investigates possible associations between paternal occupational exposure and childhood leukaemia in Great Britain. METHODS: The National Registry of Childhood Tumours provided all cases of childhood leukaemia born and diagnosed in Great Britain between 1962 and 2006. Controls were matched on sex, period of birth and birth registration subdistrict. Fathers' occupations were assigned to 1 or more of 33 exposure groups. Social class was derived from father's occupation at the time of the child's birth. RESULTS: A total of 16 764 cases of childhood leukaemia were ascertained. One exposure group, paternal social contact, was associated with total childhood leukaemia (odds ratio 1.14, 1.05-1.23); this association remained significant when adjusted for social class. The subtypes lymphoid leukaemia (LL) and acute myeloid leukaemia showed increased risk with paternal exposure to social contact before adjustment for social class. Risk of other leukaemias was significantly increased by exposure to electromagnetic fields, persisting after adjustment for social class. For total leukaemia, the risks for exposure to lead and exhaust fumes were significantly <1. Occupationally derived social class was associated with risk of LL, with the risk being increased in the higher social classes. CONCLUSION: Our results showed some support for a positive association between childhood leukaemia risk and paternal occupation involving social contact. Additionally, LL risk increased with higher paternal occupational social class.

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 child's 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.

Paternal occupation and neuroblastoma: a case-control study based on cancer registry data for Great Britain 1962-1999.

BACKGROUND: Neuroblastoma is the most common malignancy of infancy but little is known about the aetiological factors associated with the development of this tumour. A number of epidemiological studies have previously examined the risk associated with paternal occupational exposures but most have involved small numbers of cases. Here we present results from a large, population-based, case-control study of subjects diagnosed over a period of more than 30 years and recorded in the national registry of childhood tumours in Great Britain. METHODS: A case-control study of paternal occupational data for 2920 cases of neuroblastoma, born and diagnosed in Great Britain between 1962 and 1999 and recorded in the National Registry of Childhood Tumours, and 2920 controls from the general population matched on sex, date of birth and birth registration district. Paternal occupations at birth, of the case or control child, were grouped by inferred exposure using an occupational exposure classification scheme. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CI), for each of the 32 paternal occupational exposure groups. RESULTS: Only paternal occupational exposure to leather was statistically significantly associated with neuroblastoma, OR=5.00 (95% CI 1.07-46.93). However, this association became non-significant on correction for multiple testing. CONCLUSION: Our findings do not support the hypothesis that paternal occupational exposure is an important aetiological factor for neuroblastoma.

Cancer in the offspring of female radiation workers: a record linkage study.

This study uses record linkage between the National Registry of Childhood Tumours (NRCT) and the National Registry for Radiation Workers to re-assess our earlier finding that the offspring of women radiation workers exposed to ionising radiation before the child's conception may be at an increased risk of childhood cancer. An additional 16,964 childhood cancer patients taken from the NRCT, together with the same number of matched controls, are included. Pooled analyses, based on the new and original datasets, include 52,612 cases and their matched controls. Relative risks (RRs) for maternal employment as a radiation worker, maternal exposure or not during the relevant pregnancy and pattern of employment relative to conception and diagnosis dates were calculated.The new data provide no evidence of an increased risk of childhood cancer associated with maternal preconception radiation work and thus do not support our earlier finding of a raised risk in the offspring of female radiation workers. Considering the pooled data, a weak association was found between maternal radiation work during pregnancy and childhood cancer in offspring although the evidence is limited by the small numbers of linked cases and controls.

Wilms tumour and paternal occupation: an analysis of data from the National Registry of Childhood Tumours.

BACKGROUND: Wilms tumour is an embryonal malignant tumour that accounts for 90% of childhood kidney cancers. Parental occupational exposure has been hypothesised to be a cause of childhood Wilms tumour, in particular exposure to pesticides. However, the findings are inconsistent. PROCEDURE: We have examined the association between paternal occupational exposures and Wilms tumour using birth registration data for cases (n = 2568) from the National Registry of Childhood Tumours (NRCT) and matched controls (n = 2,568) drawn from the general population of Great Britain. Paternal occupation, as recorded at the time of birth, was used to infer "occupational exposure" using a previously defined occupational exposure classification scheme. Odds ratios and 95% confidence intervals were generated using conditional logistic regression with exact methods to estimate the association between each paternal occupational exposure group and childhood Wilms tumour. RESULTS: All odds ratios were close to 1.00 and no statistically significant associations were observed. CONCLUSION: The results of this study failed to support any of the previously identified associations between paternal occupation and childhood Wilms tumour.

Paternal occupation and retinoblastoma: a case-control study based on data for Great Britain 1962-1999.

OBJECTIVES: To examine the association between paternal occupational exposures and retinoblastoma using birth registration data for cases from the National Registry of Childhood Tumours (NRCT) and controls from the general population of Great Britain. METHODS: A case-control study of paternal occupational data for 1318 cases of retinoblastoma, born and diagnosed in Great Britain between 1962 and 1999, and 1318 controls matched on sex, date of birth and birth registration sub-district. Paternal occupations at birth were grouped according to inferred exposure using an occupational exposure classification scheme. A conditional (matched) case-control analysis was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for each paternal occupational exposure group. RESULTS: For non-heritable retinoblastoma, a statistically significant increased risk was found with father's definite occupational exposure to oil mists in metal working (OR = 1.85 (95% CI 1.05 to 3.36)). Together with a (non-significant) risk (OR = 1.64 (0.73 to 3.83)) amongst the heritable cases, this occupational exposure was also associated with a significant increased risk when all retinoblastoma cases were considered together (OR = 1.77 (1.12 to 2.85)). No statistically significant associations were observed for other exposure groups. CONCLUSIONS: Our finding for exposure to oil mists in metal working (a subset of metal workers) is not directly comparable to those for metal working previously reported in the literature. Overall, our findings do not support the hypothesis that paternal occupational exposure is an important aetiological factor for retinoblastoma, however, the study has low power and other methodological limitations.

Childhood leukaemia near British nuclear installations: methodological issues and recent results.

In 2008, the German Childhood Cancer Registry published the results of the Kinderkrebs in der Umgebung von Kernkraftwerken (KiKK) study of childhood cancer and leukaemia around German nuclear power stations. The positive findings appeared to conflict with the results of a recent British analysis carried out by the Committee on Medical Aspects of Radiation in the Environment (COMARE), published in 2005. The present paper first describes the COMARE study, which was based on data from the National Registry of Children's Tumours (NRCT); in particular, the methodology used in this study is described. Although the results of the COMARE study were negative for childhood leukaemia, this apparent discrepancy could be accounted for by a number of differences in approach, especially those relating to the distances from the power stations and the ages of the children studied. The present study was designed to match the KiKK study as far as possible. The incidence observed (18 cases within 5 km against 14.58 expected, p = 0.21) was not significantly raised. The risk estimate for proximity in the regression fitted was actually negative, though the confidence intervals involved are so wide that the difference from that reported in the KiKK study is only marginally statistically significant (p = 0.063).

Controlling for socioeconomic confounding using regression methods.

STUDY OBJECTIVE: To describe the advantages of using Poisson regression methods as an alternative to standardisation when computing expected numbers of disease occurrences adjusted for possible confounding factors. The problem of assessing the adequacy of model fit when the expectations are small is addressed by analytical calculations and by simulation. The method is illustrated with data from the national register of childhood tumours. DESIGN: The tumour data are recorded in a national register. SETTING: England, Scotland, and Wales. SUBJECTS: The cases considered are all children registered with leukaemia or non-Hodgkin lymphoma under the age of 15 years between 1966-87. MAIN RESULTS: The methods show a significant variation of leukaemia incidence in relation to the Register General's standard region and a negative association with socioeconomic deprivation, as measured by the Townsend index. After allowing for these variables, the incidence seems to be reasonably homogeneous throughout the population, in the sense that the residual deviance does not seem to be much larger than would be expected by chance. CONCLUSIONS: The methods described have major advantages over standardisation in controlling for confounding, both in terms of flexibility of factor selection and assessment and also in the ability to determine whether there is residual variability of incidence after allowing for these factors.