Space‐time clustering and bone tumours: Application of Knox's method to data from a population‐based cancer registry

Silcocks, Paul; Murrells, Trevor

doi:10.1002/ijc.2910400610

Cited by 9 publications

(3 citation statements)

References 24 publications

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“…Previous studies of clustering amongst non‐CNS solid tumours have suffered from methodological limitations 8, 11. A study, from the UK, covering the period 1953–6425 did not find clustering amongst solid tumours, but that study did not consider diagnostic sub‐type.…”

Section: Discussionmentioning

confidence: 98%

“…There have been a number of studies that have applied formal statistical methods9, 10 to population‐based incidence and mortality data on childhood non‐CNS solid tumours,8, 11 but these studies were inadequate for the following reasons: 1) lack of reliable diagnostic data leading to inaccurate or inappropriate classification of cases; 2) some of the studies were based on time and location at death and these will suffer from incompleteness and assume (most probably incorrectly) that the aetiological factor is present close to time of death; and 3) limitations of the statistical methods employed.…”

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confidence: 99%

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Space‐time clustering patterns in childhood solid tumours other than central nervous system tumours

McNally

Kelsey

Eden³

et al. 2002

Intl Journal of Cancer

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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. The aetiology of solid tumours, other than central nervous system tumours (non-CNS solid tumours) in children is far from clear. There are 2 possible general mechanisms: genetic susceptibility and environmental exposures. The very early age of onset and the embryonal nature of many non-CNS solid tumours of childhood suggest a prenatal origin for most, if not all, of these tumours and genetic factors are likely to be important. 1 Mutations in a number of tumour suppressor genes confer increased risk for certain embryonal tumours but inherited single gene defects would account for a small minority of cases only. De novo germline mutations in affected children have been reported, 2-7 however, and the possibility that parental pre-conceptional exposures might give rise to such mutations should be considered. Although it is likely that high penetrance genes play a role in a minority of cases, other low penetrance genes and gene-environment interactions may be important and pre-or post-natal exposure of a genetically susceptible child might also be a factor.A number of statistically significant associations between certain parental occupations or occupational exposures and childhood non-CNS solid tumour risk have been reported. Associations with parental exposures may indicate parental germ cell mutation or transplacental exposure of the fetus. These parental associations include: exposure to pesticides, metals, chemicals, solvents, petroleum products, paints, pigments, plastic and resin fumes and maternal use of sex hormones before or during the index pregnancy. 8 There is inconsistency, however, between studies and relative risks for the noted associations were all small.Certain environmental agents, including industrial and traffic pollution, pesticides and infections, are likely to occur at localised geographical points at certain times or time periods. If such agents are involved in the aetiology of specific childhood non-CNS solid tumours, pre-conceptionally, pre-natally or post-natally, the distribution of cases may exhibit space-time clustering. Space-time clustering is said to occur when excess numbers of cases are observed within various small geographical locations, but only at limited points in time. Such clustering should occur amongst particular diagnostic types sharing a common aetiology.There have been a number of studies that have applied formal statistical methods 9,10 t...

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Section: Discussionmentioning

confidence: 98%

mentioning

confidence: 99%

Space‐time clustering patterns in childhood solid tumours other than central nervous system tumours

McNally

Kelsey

Eden³

et al. 2002

Intl Journal of Cancer

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“…and underlying diseases of the bone such as Paget's disease [11]. Antenatal and childhood exposures to viral infections have not shown to be associated with the risk of developing osteosarcoma and little or no space-time clustering, suggestive of an infectious aetiology, has been seen [12][13][14][15].…”

Section: Introductionmentioning

confidence: 96%

Relationship between height at diagnosis and bone tumours in young people: a meta-analysis

Arora

Kontopantelis

Alston

et al. 2011

Cancer Causes Control

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Ak NEAREST NEIGHBOUR TEST FOR SPACE-TIME INTERACTION

1996

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This paper describes a k nearest neighbour statistic sensitive to the pattern of cases expected of space-time clusters of health events. The Knox and Mantel tests are frequently used for space-time clustering but have two disadvantages. First, the selection of critical space-time distances for the Knox test and of a data transformation for the Mantel test is subjective. Second, the Mantel statistic is the sum of the products of space and time distances, is linear in form, and is not sensitive to non-linear associations between small space and time distances expected of contagious processes. The k nearest neighbour statistic is the number of case pairs that are k nearest neighbours in both space and time, and is evaluated under the null hypothesis of independent space and time nearest neighbour relationships. The test was applied to simulated and real data and compared to the Knox and Mantel tests using statistical power comparisons. The k nearest neighbour test proved sensitive to the space-time interaction pattern expected of disease clusters, does not require parameters (such as critical distances) to be estimated from the data, and may be used to test hypotheses about the spatial and temporal scale of the cluster process. The method addresses significant weaknesses in existing space-time cluster tests and should prove useful in the quantification and evaluation of clusters of human health events. Additional research is needed to further document the power of the test under different cluster processes.

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Space‐time clustering and bone tumours: Application of Knox's method to data from a population‐based cancer registry

Cited by 9 publications

References 24 publications

Space‐time clustering patterns in childhood solid tumours other than central nervous system tumours

Space‐time clustering patterns in childhood solid tumours other than central nervous system tumours

Relationship between height at diagnosis and bone tumours in young people: a meta-analysis

Ak NEAREST NEIGHBOUR TEST FOR SPACE-TIME INTERACTION

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