French Amy E, Grant Ron, Weitzman Sheila, Ray Joel G, Vermeulen Marian J, Sung Lillian, Greenberg Mark, Koren Gideon
Motherrisk Program and Division of Hematology and Oncology, The Hospital for Sick Children, and Department of Medicine and Prehospital Care Programme, Sunnybrook and Women's College Health Sciences Center, University of Toronto, Ontario, Canada.
Clin Pharmacol Ther. 2003 Sep;74(3):288-94. doi: 10.1016/S0009-9236(03)00200-5.
Neuroblastoma, an embryonic tumor, is the second most common pediatric tumor and is the most prevalent extracranial solid tumor in children. Results of previous studies have suggested that maternal vitamin intake may decrease the risk of several childhood cancers. In January 1997, Canada began fortifying flour with folic acid for the prevention of neural tube defects. The effect of folic acid fortification on the rate of neuroblastoma in offspring is not known.
We investigated the rates of neuroblastoma (<1 year), acute lymphoblastic leukemia, and hepatoblastoma registered by the Pediatric Oncology Group of Ontario, which captures 95% of all pediatric cancers in Ontario, before and after the introduction of folate fortification.
An interventional time series analysis showed that the incidence of neuroblastoma declined from 1.57 cases per 10,000 births before to 0.62 case per 10,000 births after folic acid fortification (P <.0001). The crude incidence rate ratio (0.40; 95% confidence interval, 0.25-0.64) remained significant after adjustment for both age and disease stage at diagnosis (adjusted incidence rate ratio, 0.38; 95% confidence interval, 0.23-0.62). In contrast, there was no significant change in the rate of infant acute lymphoblastic leukemia (incidence rate ratio, 0.97; 95% confidence interval, 0.41-2.27) or hepatoblastoma (incidence rate ratio, 0.81; 95% confidence interval, 0.35-1.89).
Folic acid fortification was associated with a 60% reduction in neuroblastoma but was not associated with any change in the rate of infant acute lymphoblastic leukemia or hepatoblastoma. Further investigation is needed into the role of metabolism in the formation and prevention of neuroblastoma and other embryonically determined cancers.
神经母细胞瘤是一种胚胎性肿瘤,是儿童期第二常见的肿瘤,也是儿童中最常见的颅外实体瘤。先前的研究结果表明,母亲摄入维生素可能会降低几种儿童癌症的风险。1997年1月,加拿大开始在面粉中添加叶酸以预防神经管缺陷。叶酸强化对后代神经母细胞瘤发病率的影响尚不清楚。
我们调查了安大略省儿科肿瘤学组登记的神经母细胞瘤(<1岁)、急性淋巴细胞白血病和肝母细胞瘤的发病率,该组涵盖了安大略省95%的儿童癌症病例,时间为叶酸强化前后。
一项干预性时间序列分析显示,神经母细胞瘤的发病率从叶酸强化前的每10000例出生1.57例降至强化后的每10000例出生0.62例(P<.0001)。在对诊断时的年龄和疾病分期进行调整后,粗发病率比(0.40;95%置信区间,0.25 - 0.64)仍然显著(调整后的发病率比,0.38;95%置信区间,0.23 - 0.62)。相比之下,婴儿急性淋巴细胞白血病的发病率(发病率比,0.97;95%置信区间,0.41 - 2.27)或肝母细胞瘤的发病率(发病率比,0.81;95%置信区间,0.35 - 1.89)没有显著变化。
叶酸强化与神经母细胞瘤发病率降低60%相关,但与婴儿急性淋巴细胞白血病或肝母细胞瘤的发病率变化无关。需要进一步研究代谢在神经母细胞瘤和其他胚胎性癌症形成及预防中的作用。