A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: A hypothesis
A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: A hypothesis
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DOI：
10.1158/1055-9965.epi-07-0329
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发表时间：
2007-07-01
影响因子：
3.8
通讯作者：
Rosenberg, Irwin H.
中科院分区：
文献类型：
--
作者：
Mason, Joel B.;Dickstein, Aaron;Rosenberg, Irwin H.
美国和加拿大分别于1996年和1997年开始在全国范围内用叶酸强化未经烹饪的谷物，并于1998年成为强制性规定。其基本原理是减少神经管缺陷的出生数量。与此同时，美国和加拿大经历了结肠直肠癌（CRC）发病率下降趋势的突然逆转，这两个国家在过去十年中享有：1996年，CRC的绝对发病率开始上升（美国）和1998年（加拿大），1998年达到顶峰（美国）和2000年（加拿大），并继续超过1996/1997年前的趋势，每10万人增加4至6例。在每个国家，CRC发病率相对于强化前趋势的增加福尔斯显著超出基于非参数95%置信区间的向下线性拟合。如果对每个国家的数据分别按男女进行分析，统计上的显著增长也是显而易见的。结直肠内镜手术率的变化似乎不能解释结直肠癌发病率的增加。这些观察结果本身并不能证明因果关系，但与临床前和临床研究中显示的叶酸对现有肿瘤的已知作用一致。因此，我们推测叶酸强化制度可能是20世纪90年代中期观察到的CRC发病率增加的全部或部分原因。需要进一步开展工作，以最终确定这种关系的性质。与此同时，在审议制定或加强强化计划时，应考虑到这些因素。
Nationwide fortification of enriched uncooked cereal grains with folic acid began in the United States and Canada in 1996 and 1997, respectively, and became mandatory in 1998. The rationale was to reduce the number of births complicated by neural tube defects. Concurrently, the United States and Canada experienced abrupt reversals of the downward trend in colorectal cancer (CRC) incidence that the two countries had enjoyed in the preceding decade: absolute rates of CRC began to increase in 1996 (United States) and 1998 (Canada), peaked in 1998 (United States) and 2000 (Canada), and have continued to exceed the pre-1996/1997 trends by 4 to 6 additional cases per 100,000 individuals. In each country, the increase in CRC incidence from the prefortification trend falls significantly outside of the downward linear fit based on nonparametric 95% confidence intervals. The statistically significant increase in rates is also evident when the data for each country are analyzed separately for men and women. Changes in the rate of colorectal endoscopic procedures do not seem to account for this increase in CRC incidence. These observations alone do not prove causality but are consistent with the known effects of folate on existing neoplasms, as shown in both preclinical and clinical studies. We therefore hypothesize that the institution of folic acid fortification may have been wholly or partly responsible for the observed increase in CRC rates in the mid-1990s. Further work is needed to definitively establish the nature of this relationship. In the meantime, deliberations about the institution or enhancement of fortification programs should be undertaken with these considerations in mind.