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Background: The aetiology of neuroblastic tumours is likely to involve both genetic and environmental factors. A number of possible environmental risk factors have been suggested, including infection. If an irregular temporal pattern in incidence is found, this might suggest that a transient agent, such as an infection, is implicated. Previous work has found evidence for temporal clustering in children and young adults living in northern England., Methods: We examined data from a second population-based registry from Ontario, Canada to determine whether there was evidence of temporal clustering of neuroblastic tumours. Cases diagnosed in children and young adults aged 0-19 years between 1985 and 2016 were extracted from the population-based Pediatric Oncology Group of Ontario Networked Information System (POGONIS). A modified version of the Potthoff-Whittinghill method was used to test for temporal clustering. Estimates of extra-Poisson variation (EPV) and standard errors (SE) were obtained., Results: Eight hundred seventy-six cases of neuroblastic tumours were diagnosed during the study period. Overall, no evidence of temporal clustering was found between fortnights, between months or between quarters within years. However, significant EPV was found between years within the full study period (EPV = 1.05, SE = 0.25; P = 0.005)., Conclusions: The findings are consistent with the possibility that a transient agent, such as an infection that is characterised by 'peaks and troughs' in its occurrence, might be implicated in the aetiology of neuroblastic tumours. However, this pattern may also reflect a long-term increase in the numbers of cases, rather than peaks and troughs., (© 2022. The Author(s).)

Previously excesses in incident cases of leukaemia and non-Hodgkin lymphoma have been observed amongst young people born or resident in Seascale, Cumbria. These excesses have not been seen more recently. It is postulated that the former apparent increased risk was related to 'unusual population mixing', which is not present in recent years. This study investigated changes in measures of population mixing from 1951-2001. Comparisons were made between three specified areas. Area-based measures were calculated (migration, commuting, deprivation, population density). All areas have become more affluent, although Seascale was consistently the most affluent. Seascale has become less densely populated, with less migration into the ward and less diversity with respect to migrants' origin. There have been marked changes in patterns of population mixing throughout Cumbria. Lesser population mixing has been observed in Seascale in recent decades. Changes in pattern and nature of population mixing may explain the lack of recent excesses., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Previously, we identified space-time clustering in certain childhood cancers. This study aimed to determine whether there was cross-space-time clustering between different diagnostic groups. A total of 32,295 cases were diagnosed during 1969-1993. Cross-space-time clustering was analyzed by a second-order procedure based on Diggle's method. Locations were birth and diagnosis addresses. The following space-time combinations were examined: address and date of birth; address at birth and date of diagnosis; address and date of diagnosis. Cross-space-time clustering analyses considered clustering pairs of cases from two different diagnostic groups. Formal statistical significance was taken as p < 0.00067 and marginal significance 0.01 > p ≥ 0.00067. Based on address at birth and date of diagnosis, there was statistically significant cross-clustering between cases of HL and intracranial and intraspinal embryonal tumors (IIET), both aged 0-14 years (p < 0.0001). Based on address and date of birth, there was marginally significant cross-clustering between cases of lymphoid leukemia (LL) aged 5-14 years and Hodgkin lymphoma (HL) aged 0-14 years (p = 0.0019). Based on address and date of diagnosis there was marginally significant cross-clustering between cases of LL aged 1-4 years and soft tissue sarcoma (STS) aged 0-14 years (p = 0.0041). Findings from this study are consistent with possible common aetiological factors between different diagnostic groups. They suggest a common aetiology for the following pairs of diagnostic groups: HL and IIET; older cases of LL and HL; younger cases of LL and STS. The possibility of common infectious mechanisms should be explored., (© 2013 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.)

The aim of this study was to investigate seasonal variation in the incidence of cancer in children aged 0-14 years. Details of 2959 primary malignant cases (1659 males, 1300 females), diagnosed during the period 1968-2005, were extracted from a specialist registry (the Northern Region Young Persons' Malignant Disease Registry). Seasonal variation was analysed with respect to month of birth and diagnosis. The chi-squared heterogeneity test was used to test for non-uniform variation. Poisson regression analysis was used to fit sinusoidal (harmonic) models to the data, using month of birth and month of diagnosis, respectively, as covariates in separate models. There was significant sinusoidal variation based on month of birth for acute lymphoblastic leukaemia (ALL) aged 1-6 years (P = 0.04; peak in March). For 0- to 14-year-old boys, there was statistically significant sinusoidal variation in month of birth for acute non-lymphocytic leukaemia (P = 0.04; peak in September) and astrocytoma (P = 0.03; peak in October). Based on month of diagnosis, there was statistically significant sinusoidal variation in girls for all lymphomas (P = 0.048; peak in March) and Hodgkin lymphoma (HL) (P = 0.005; peak in January), and in boys for osteosarcoma (P = 0.049; peak in October). This study confirms previous findings of seasonal variation around the month of birth for childhood ALL (at the peak ages) and provides further evidence of seasonal variation around month of birth for astrocytoma and around month of diagnosis for HL. The results are consistent with a role for environmental factors in the aetiology of these diagnostic groups. Further studies are needed to examine putative candidate agents.

The aetiology of childhood cancer is poorly understood. Both genetic and environmental factors are likely to be involved. The presence of spatial clustering is indicative of a very localized environmental component to aetiology. Spatial clustering is present when there are a small number of areas with greatly increased incidence or a large number of areas with moderately increased incidence. To determine whether localized environmental factors may play a part in childhood cancer aetiology, we analyzed for spatial clustering using a large set of national population-based data from Great Britain diagnosed 1969-1993. The Potthoff-Whittinghill method was used to test for extra-Poisson variation (EPV). Thirty-two thousand three hundred and twenty-three cases were allocated to 10,444 wards using diagnosis addresses. Analyses showed statistically significant evidence of clustering for acute lymphoblastic leukaemia (ALL) over the whole age range (estimate of EPV = 0.05, p = 0.002) and for ages 1-4 years (estimate of EPV = 0.03, p = 0.015). Soft-tissue sarcoma (estimate of EPV = 0.03, p = 0.04) and Wilms tumours (estimate of EPV = 0.04, p = 0.007) also showed significant clustering. Clustering tended to persist across different time periods for cases of ALL (estimate of between-time period EPV = 0.04, p =0.003). In conclusion, we observed low level spatial clustering that is attributable to a limited number of cases. This suggests that environmental factors, which in some locations display localized clustering, may be important aetiological agents in these diseases. For ALL and soft tissue sarcoma, but not Wilms tumour, common infectious agents may be likely candidates.

Previously, we identified space-time clustering in certain childhood cancers around diagnosis residence. These findings provided support for the involvement of environmental agents in etiological processes occurring close to diagnosis. We have reanalyzed the same British population-based dataset. The aim of the study was to determine whether there was space-time clustering around the residence at birth in relation to time of birth and separately from time of diagnosis. A total of 29,553 cases, diagnosed during the period 1969-1993, were examined by a second-order procedure based on K-functions. Locations were birth addresses, but separately, both dates of birth and diagnosis were analyzed. There was statistically significant space-time clustering for Hodgkin lymphoma (HL) and central nervous system (CNS) tumors (p=0.047 and 0.01, respectively, based on birth date) and for total leukemia at ages 1-4 years only, Non-Hodgkin lymphoma (NHL) and Wilms tumor (p=0.01, 0.02 and 0.006, respectively, based on diagnosis date). These results, interpreted together with other epidemiological evidence, suggest an etiological role for environmental factors focused around birth address for certain childhood cancers. For HL and CNS tumors, findings suggest that etiological exposures occurred at similar ages or in utero. For leukemia, NHL and Wilms tumor there is support for exposures occurring at similar times before diagnosis. For leukemia, HL, NHL and CNS tumors, but not Wilms tumor, the findings are consistent with infectious hypotheses., (Copyright (c) 2008 Wiley-Liss, Inc.)

Background: Numerous studies have implied that paternal occupational exposures, in particular electromagnetic fields (EMF) and ionizing radiation, may be involved in the etiology of childhood cancers. We investigated whether an association exists between paternal occupations at birth involving such exposures and cancer risk in offspring, using data from the Northern Region Young Persons' Malignant Disease Registry (NRYPMDR)., Procedure: Cases (n=4,723) were matched, on sex and year of birth, to controls from two independent sources: (i) all other patients from the NRYPMDR with a different cancer, (ii) 100 cancer-free individuals per case from the Cumbrian Births Database. An occupational exposure matrix was used to assign individuals to exposure groups., Results: There was an increased risk of leukemia among the offspring of men employed in occupations likely to be associated with EMF or radiation exposures (OR 1.31, 95% CI 1.02-1.69), particularly in males aged less than 6 years (OR 1.81, 95% 1.19-2.75). No significant association was seen in females. Increased risks were also seen for chondrosarcoma (OR 8.7, 95% CI 1.55-49.4) and renal carcinoma (OR 6.75, 95% CI 1.73-26.0). These associations were consistent between control groups and remained after adjustment for socio-economic status., Conclusions: This large case-control study identified a significantly increased risk of leukemia among the offspring of men likely to have been occupationally exposed to EMF, with differing associations between males and females. Increased risks of chondrosarcoma and renal carcinoma were also seen, although based on smaller numbers. Further detailed investigations in this area are required to understand this association., (Copyright (c) 2006 Wiley-Liss, Inc.)

Previous studies have provided evidence that infections may play a part in the aetiology of certain childhood cancers. The finding of space-time clustering indicates the presence of an environmental component to aetiology and is especially supportive of a role for infections. Space-time clustering occurs when excess numbers of cases of a disease are observed within small geographical locations at limited periods of time and this cannot be explained in terms of general excesses in those locations or at those times. To investigate whether infections may be involved in the aetiology of childhood cancer, we have analysed for space-time clustering using a large set of national population-based data from Great Britain for the period 1969-1993. Data were examined by a second-order procedure based on K-functions, with fixed thresholds of closeness in space (0.5-7.5 km) and closeness in time (0.1-1.5 years). Locations were addresses at diagnosis. Tests were repeated, replacing geographical distances with distances to the 19th-33rd nearest neighbours and this provided the primary result for each analysis. There were a total of 32,295 cases of childhood cancer. The analyses showed statistically significant evidence of space-time clustering for acute lymphoblastic leukaemia over the whole age range (p = 0.04), but especially for ages 1-4 years (p = 0.03). There was less statistically significant evidence for total leukaemia (p = 0.048). Significant space-time clustering was also evident for soft tissue sarcomas (p = 0.03) and osteosarcomas (p = 0.02). Results support other evidence suggesting a role for infections in the aetiology of these particular diagnostic groups.

Researchers in numerous studies have suggested that preconception paternal occupational exposures to various substances, including pesticides and herbicides, may be involved in the etiology of childhood cancers. Using data from the Northern Region Young Persons' Malignant Disease Registry, the authors investigated whether paternal occupations likely to involve such exposures, as recorded at the time of a child's birth, were associated with children's cancer risk. The authors matched cases (n = 4,723), on sex and year of birth, to controls from 2 independent sources: (1) all other patients from the registry with a different cancer and (2) 100 cancer-free individuals per case from the Cumbrian Births Database. An inverse association existed, particularly in males, between lymphoid leukemia and paternal occupations with likely exposures to pesticides and/or herbicides. However, this was not significant after stratifying by residential status (urban versus rural). Results do not support a role for preconception paternal occupational exposures to pesticides or herbicides in the etiology of childhood cancer.

We previously demonstrated significant space-time clustering amongst cases of childhood leukaemia (in particular acute lymphoblastic leukaemia (ALL)), central nervous system (CNS) tumour (especially astrocytoma), soft tissue sarcoma and Wilms' tumour. We hypothesised that there may be common aetiological mechanisms between some of these diagnostic groups. To test this hypothesis we analysed for cross-space-time clustering between these diagnostic groups, using population-based data from north-west England. Data were examined by a second-order procedure based on K-functions. Reference points in time and space were dates and addresses at birth and diagnosis. The results showed statistically significant (P < 0.05) cross-clustering between cases of leukaemia and CNS tumour and between cases of ALL and astrocytoma. There was no statistically significant cross-clustering of Wilms' tumours and soft tissue sarcomas with any other malignancy. In conclusion, these findings are consistent with common, possibly infectious, aetiological mechanisms for childhood leukaemia (particularly ALL) and CNS tumours (particularly astrocytoma).

The aetiology of most childhood solid tumours (other than central nervous system [CNS] tumours) is unclear. To investigate whether certain environmental exposures may be involved, we have analysed for space-time clustering using population-based data from North West England for the period 1954-98. Knox tests for space-time interactions between cases were applied with fixed thresholds of close in space, <5 km, and close in time, <1 year apart. Addresses at birth and at diagnosis were used. Tests were repeated replacing geographical distance with distance to the Nth nearest neighbour. N was chosen such that the mean distance was 5 km. Data were also examined by a second order procedure based on K-functions. There was significant evidence of space-time clustering for Wilms' tumours (p = 0.03 and 0.04, using the geographical distance and nearest neighbour versions of the Knox test; and p = 0.07 and 0.03, using the geographical distance and nearest neighbour versions of the K-function method), and soft tissue sarcomas (p = 0.01, using both the geographical distance and nearest neighbour versions of the Knox test; and p = 0.001 and 0.002, using the geographical distance and nearest neighbour versions of the K-function method) based on time and location at birth, but not time and location at diagnosis. There was little or no evidence of space-time clustering amongst other diagnostic groups. These are the first results to demonstrate space-time clustering for childhood Wilms' tumours and soft tissue sarcomas. The results are consistent with environmental exposure hypotheses, relating to locations pre-natally or peri-natally., (Copyright 2003 Wiley-Liss, Inc.)