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Purpose: The etiology of congenital cerebral palsy is unclear. Recent studies have suggested that maternal infection is involved. Indirect, but supportive, evidence for an infectious hypothesis would be provided by the finding of space-time clustering., Methods: We analyzed all 906 cases born during the period 1991-2003 using a population-based registry from Northern England. We applied the K-function method for testing global space-time clustering and used residential addresses at the time of birth. The Knox method was used to determine the spatio-temporal range over which global clustering occurred. Tests were repeated using nearest neighbor thresholds to allow for variable population density. Additionally, Kulldorff's scan statistic identified specific space-time clusters., Results: There was statistically significant evidence of global space-time clustering (p

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.

Objective: To study the distribution of septo-optic dysplasia (SOD) and optic nerve hypoplasia (ONH) in the Greater Manchester and Lancashire (GM&L) region of Northwest England, and to analyze occurrence by location and over time., Study Design: A population-based incidence study was undertaken for cases of SOD/ONH from GM&L. Standardized incidence ratio (SIR) for each district, relationships between SIRs and possible geographically varying risk factors, and spatial and space-time clustering were analyzed., Results: Eighty-seven cases had a confirmed diagnosis of ONH/SOD giving an incidence of 10.9/100,000 per year in GM&L. SIRs ranged widely but were significantly elevated (lower confidence limit >100) in three districts: 167%, 192%, and 198%, respectively. All three were high population density, inner-city locations. SIRs were significantly correlated with higher rates of unemployment (r = 0.49, P = .01), dependent children in non-earning households (r = 0.47, P = .02), underage conceptions (r = 0.46, P = .02), and underage pregnancies (r = 0.44, P = .03). There was no evidence of spatial or space-time clustering., Conclusions: The incidence of ONH/SOD in GM&L was higher than that reported elsewhere. Cases were more common in areas that had higher unemployment and teenage pregnancy rates.

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).

Previously, we reported space-time clustering and seasonal variation in childhood central nervous system (CNS) tumours for the period 1954-1998. These previous studies provided evidence that infections may be involved in aetiology. To determine whether there were also localised spatial factors involved in aetiology we analysed the geographical distribution of CNS tumours in children aged 0-14 years using Manchester Children's Tumour Registry (MCTR) data for the period 1976-2000. Specifically, the Potthoff-Whittinghill test for spatial clustering was applied and Poisson regression was used to analyse the relationship between incidence rates and small-area population density, ethnic composition and deprivation index. No relationships were seen for all CNS tumours together and only a few for the subgroups. The previous findings of space-time clustering and seasonal variation, involving astrocytoma and ependymoma, together with the lack of spatial clustering and ecological relationships for these tumours provide evidence that astrocytoma and ependymoma may be associated with a highly mobile transient aetiological agent. An example of such an agent is an infection that occurs in mini-epidemics.

The aim of this paper was to study the geographical distribution of Wilms' tumours (WT) and soft-tissue sarcomas (STS) for 0-14 year olds included in a population-based registry from North West England during 1976-2000. Standardised morbidity ratios (SMRs) were calculated. Relationships between incidence rates and small area (ward) population density, ethnic composition, deprivation index and urban-rural status were examined using Poisson regression. There was a non-linear relationship between WT incidence and population density (P=0.008), with a higher incidence associated with wards with low deprivation scores (P=0.02); and which included a greater proportion of whites (P=0.01). For STS, a higher incidence was associated with wards with low deprivation scores (P=0.04); and which were 'more rural/less urban' (P=0.03). These results are consistent with a role for localised environmental exposures, in combination with lifestyle factors, in the aetiology of WT. For STS, there is some evidence for the involvement of environmental and/or lifestyle factors.

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.)