Knox E G, Gilman E A
Department of Public Health and Epidemiology, University of Birmingham.
J Epidemiol Community Health. 1996 Jun;50(3):313-9. doi: 10.1136/jech.50.3.313.
Firstly, to identify spatially close pairs and triplets of childhood leukaemias and cancers in Britain. Secondly, to compare pair frequencies with random expectations, identify excesses, and measure the diameters of any clusters. Thirdly, to infer possible causes.
Stratified Poisson analyses of two comprehensive sets of childhood leukaemia and cancer data in Great Britain: seeking home address pairs within particular census enumeration districts (EDs) or postcodes (PCs). Numbers of pairs/triplets of leukaemia registrations sharing single or adjacent EDs were compared with Poisson, expectations in national ED strata with different numbers of households (HHs). Pairs/triplets of leukaemia/cancer deaths (and births) sharing a single PC were compared with Poisson expectations in national PC strata with different numbers of postal delivery points (DPs). Same and adjacent house pairs were identified individually among the same PC death pairs. Areal case densities were estimated around a sample of index cases, using their own PC grid coordinates, and those recorded in the central PC directory.
These comprised, firstly, all cases of childhood leukaemia and non-Hodgkin lymphoma registered between 1966 and 1983 in England and Wales (ED analysis) and, secondly, all childhood leukaemia and cancer deaths between 1953 and 1980, in England, Wales, and Scotland (PC analyses at birth and at death).
Short range spatial clustering was demonstrated (a) for leukaemia at place of registration, and (b) for leukaemia and cancer (separately and jointly) at both birth and death addresses. There was evidence of additional case pairing in adjacent PCs. Both data sets showed a relative local pair excess of about 1.5, within diameters of 300 metres. Secondary case densities, measured within 600 metres of a sample of unpaired index cases, were raised by the same ratio. The raised risk then tapered with increasing distance to about 3 km. Forty-four non-twin pairs had died at exactly the same address, far in excess of random expectation. This same house excess was due entirely to 31 sibling pairs. They also showed a relative excess of central nervous system and other solid tumours; but without the exact tumour type sibling concordances sometimes seen in MZ twins. The sibling pairs were only a small part of the overall excess of same PC pairs.
Short range geographical clustering probably reflects two separate causes of childhood cancer, namely (a) an uncommon familial susceptibility to solid cancers, probably inherited, and (b) a group of long standing focal environmental hazards, most effective within a few hundred metres of the source, but detectable as far as 3 km.
第一，确定英国儿童白血病和癌症在空间上相邻的成对及三联病例。第二，将成对病例的频率与随机预期值进行比较，识别出超出预期的情况，并测量任何聚集区域的直径。第三，推断可能的病因。
对英国两套全面的儿童白血病和癌症数据进行分层泊松分析：在特定的人口普查枚举区（EDs）或邮政编码（PCs）内查找家庭住址对。将白血病登记中共享单个或相邻EDs的成对/三联病例数与泊松分布进行比较，在不同家庭数量（HHs）的国家EDs层中进行预期分析。将共享单个PC的白血病/癌症死亡（及出生）的成对/三联病例数与不同邮政投递点（DPs）数量的国家PC层中的泊松预期值进行比较。在相同PC死亡对中分别识别出相同和相邻的房屋对。使用索引病例自身的PC网格坐标以及中央PC目录中记录的坐标，估计索引病例样本周围的区域病例密度。
第一组包括1966年至1983年在英格兰和威尔士登记的所有儿童白血病和非霍奇金淋巴瘤病例（ED分析）；第二组包括1953年至1980年在英格兰、威尔士和苏格兰的所有儿童白血病和癌症死亡病例（出生和死亡时的PC分析）。
在以下方面证实了短程空间聚集现象：（a）登记地点的白血病；（b）出生和死亡地址处的白血病和癌症（分别及共同）。有证据表明相邻PC中存在额外的病例配对。两个数据集均显示，在直径300米范围内，相对局部成对病例超出约1.5倍。在未配对索引病例样本600米范围内测量的继发病例密度也以相同比例升高。随着距离增加到约3公里，升高的风险逐渐减弱。44对非双胞胎在完全相同的地址死亡，远远超过随机预期。这种相同房屋地址的超出完全归因于31对兄弟姐妹。他们还显示中枢神经系统和其他实体瘤相对增多；但没有同卵双胞胎中有时出现的精确肿瘤类型的兄弟姐妹一致性。兄弟姐妹对只是同一PC对总体超出的一小部分。
短程地理聚集可能反映了儿童癌症的两个独立病因，即（a）对实体癌不常见的家族易感性，可能是遗传的；（b）一组长期存在的局部环境危害，在距离源头几百米内最为有效，但在3公里范围内仍可检测到。
