Milne Elizabeth, Laurvick Crystal L, Blair Eve, de Klerk Nicholas, Charles Adrian K, Bower Carol
Telethon Institute for Child Health Research, Centre for Child Health Research,The University of Western Australia, Perth, Western Australia.
Princess Margaret Hospital and King Edward Memorial Hospital for Women, Subiaco, Perth, Western Australia.
Int J Cancer. 2008 Jul 15;123(2):436-443. doi: 10.1002/ijc.23486.
The etiology of childhood cancers is largely unknown, although the early age at diagnosis has led to particular interest in in utero and perinatal factors. Birth weight is the most frequently studied perinatal factor in relation to risk of childhood cancers, and results have been inconsistent. We investigated whether the risk of CNS tumors and lymphomas in children was associated with three measures of the appropriateness of intra-uterine growth: proportion of optimal birth weight (POBW), birth length (POBL) and weight for length (POWFL). A cohort of 576,633 infants born in Western Australia in 1980-2004 were followed from birth to diagnosis of a CNS tumor (n = 183) or lymphoma (n = 84) before age 15, death, or December 31, 2005, and analyzed with Cox regression. Overall, there was little evidence of any association between fetal growth and risk of CNS tumors, although risk of ependymoma/choroid plexus tumors was positively associated with POBL and negatively associated with POWFL. The risk of Hodgkin and Burkitt lymphoma increased with increasing fetal growth among boys only, whereas the increased risk observed with non-Hodgkin lymphoma was only in girls. These associations between fetal growth and disease risk were also observed among children not classified as high birth weight, suggesting that accelerated growth is more important than birth weight per se. Results were similar when cases were compared with their unaffected siblings, suggesting that the increased growth associated with cancer risk was not general to the family. The associations we observed are consistent with causal pathways involving fetal growth factors.
儿童癌症的病因在很大程度上尚不清楚,尽管诊断时的低龄引发了人们对子宫内和围产期因素的特别关注。出生体重是与儿童癌症风险相关的最常被研究的围产期因素,但其结果并不一致。我们调查了儿童中枢神经系统肿瘤和淋巴瘤的风险是否与子宫内生长适宜性的三项指标相关:最佳出生体重比例(POBW)、出生身长(POBL)和身长体重比(POWFL)。对1980年至2004年在西澳大利亚出生的576,633名婴儿进行队列研究,从出生开始随访,直至诊断出15岁前的中枢神经系统肿瘤(n = 183)或淋巴瘤(n = 84)、死亡或2005年12月31日,并采用Cox回归分析。总体而言,几乎没有证据表明胎儿生长与中枢神经系统肿瘤风险之间存在任何关联,尽管室管膜瘤/脉络丛肿瘤的风险与POBL呈正相关,与POWFL呈负相关。仅在男孩中,霍奇金淋巴瘤和伯基特淋巴瘤的风险随着胎儿生长增加而升高,而非霍奇金淋巴瘤观察到的风险增加仅在女孩中出现。在未被归类为高出生体重的儿童中也观察到了胎儿生长与疾病风险之间的这些关联,这表明生长加速比出生体重本身更重要。当将病例与其未受影响的兄弟姐妹进行比较时,结果相似,这表明与癌症风险相关的生长增加并非整个家庭普遍存在的现象。我们观察到的这些关联与涉及胎儿生长因子的因果途径一致。