Alexander F E, Boyle P, Carli P M, Coebergh J W, Ekbom A, Levi F, McKinney P A, McWhirter W, Michaelis J, Peris-Bonet R, Petridou E, Pompe-Kirn V, Plĕsko I, Pukkala E, Rahu M, Stiller C A, Storm H, Terracini B, Vatten L, Wray N
Department of Public Health Sciences, University of Edinburgh, Medical School, U.K.
Eur J Cancer. 1999 Mar;35(3):439-44. doi: 10.1016/s0959-8049(98)00385-2.
The EUROCLUS study assembled incidence data for 13,551 cases of childhood leukaemia (CL) diagnosed between 1980 and 1989 in 17 countries (or regions of countries). These were referenced by location at diagnosis to small census areas of which there were 25,723 in the study area. Population counts, surface area and, hence, population density were available for all these small areas. Previous analyses have shown limited extra-Poisson variation (EPV) of case counts within small areas; this is most pronounced in areas of intermediate population density (150-499 persons/km2). In this study, the data set was examined in more detail for evidence that variations in incidence and EPV of CL are associated with population density. Incidence showed a curvilinear association with population density and was highest in areas which were somewhat more densely populated (500-750 persons/km2), where the incidence rate ratio relative to areas having > or = 1000 persons/km2 was 1.16 (95% confidence interval 1.07-1.26) and the P value for quadratic trend across eight strata of population density was 0.02. Incidence in these areas is uniformly elevated and showed no evidence of heterogeneity (i.e. EPV). Statistically significant evidence of EPV was evident amongst some of the areas previously classified as intermediate density areas (specifically, those with a density of 250-499 persons/km2, P < 0.001 for CL). These results were interpreted in terms of the current aetiological hypotheses for CL which propose that exposure to localised epidemics of one or more common infectious agent may contribute to the development of leukaemia. They suggest that such epidemics arise regularly in moderately densely populated areas and also sporadically in areas which are somewhat less densely populated. Although other interpretations are possible, these results may assist in the identification of characteristics which infectious agents must possess if direct or indirect causes of CL.
EUROCLUS研究收集了1980年至1989年间在17个国家（或国家的地区）诊断出的13551例儿童白血病（CL）的发病数据。这些数据根据诊断时的地点被引用到研究区域内的25723个小普查区域。所有这些小区域都有人口计数、表面积，因此也有人口密度数据。先前的分析表明，小区域内病例数的泊松外变异（EPV）有限；这在中等人口密度（150 - 499人/平方公里）的区域最为明显。在本研究中，对数据集进行了更详细的检查，以寻找CL发病率和EPV的变化与人口密度相关的证据。发病率与人口密度呈曲线关联，在人口稍多的地区（500 - 750人/平方公里）最高，相对于人口密度≥1000人/平方公里的地区，发病率比为1.16（95%置信区间1.07 - 1.26），并且在八个不同人口密度层中二次趋势的P值为0.02。这些地区的发病率普遍升高，且未显示出异质性（即EPV）的证据。在一些先前被归类为中等密度区域的地区（具体而言，密度为250 - 499人/平方公里的地区，CL的P < 0.001），有明显的EPV统计学显著证据。这些结果根据目前关于CL的病因假设进行了解释，该假设提出暴露于一种或多种常见传染因子的局部流行可能有助于白血病的发生。它们表明，这种流行在人口适度密集的地区经常出现，并偶尔在人口稍少的地区出现。尽管可能有其他解释，但这些结果可能有助于确定如果是CL的直接或间接病因，传染因子必须具备的特征。
