Carrier Julie, Medline Alan, Sohn Kyoung-Jin, Choi Monica, Martin Rochelle, Hwang Stephen W, Kim Young-In
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Cancer Epidemiol Biomarkers Prev. 2003 Nov;12(11 Pt 1):1262-7.
Folate supplementation may reduce the risk of colorectal dysplasia and cancer in subjects with chronic ulcerative colitis (UC). The interleukin (IL) 2- and beta(2)-microglobulin (beta(2)m)-deficient (IL-2(null) x beta(2)m(null)) mice spontaneously develop colon cancer in the setting of chronic UC. This study investigated the effects of dietary folate on the development of UC-associated colon cancer in the IL-2(null) x beta(2)m(null) mice. Weaning IL-2(null) x beta(2)m(null) mice were randomized to receive 0 (deficient; n = 40), 2 (basal requirement; control; n = 46), or 8 (supplemented; n = 36) mg folate/kg diet for 32 weeks. At necropsy, all macroscopic colonic tumors were identified and histologically classified as dysplasia or adenocarcinoma. The incidence of high-grade lesions (high-grade dysplasia/carcinoma in situ and invasive adenocarcinoma) in the folate-supplemented group was 46% lower than that in the control group (35.3% versus 65.1%, P = 0.009). The incidence of high-grade lesions in the folate-deficient group was also 49% lower than that in the control group (33.3% versus 65.1%, P = 0.007). The higher mortality rate in the folate-deficient group compared with the other two groups (25% versus 6.5% and 5.6%, P < 0.02) partially accounted for the low incidence of high-grade lesions in this group. These data indicate that dietary folate supplementation at 4x the basal dietary requirement significantly suppresses UC-associated colorectal carcinogenesis in the IL-2(null) x beta(2)m(null) mice. These data also suggest that folate deficiency may inhibit colorectal carcinogenesis in chronic UC. However, the high mortality observed in the folate-deficient group precludes a definitive conclusion concerning the effect of folate deficiency on UC-associated colorectal carcinogenesis in this model.
补充叶酸可能降低慢性溃疡性结肠炎（UC）患者发生结直肠发育异常和癌症的风险。白细胞介素（IL）2和β2微球蛋白（β2m）缺陷（IL-2(null) x β2m(null)）小鼠在慢性UC背景下会自发发生结肠癌。本研究调查了饮食中叶酸对IL-2(null) x β2m(null)小鼠UC相关结肠癌发生的影响。将断奶的IL-2(null) x β2m(null)小鼠随机分为三组，分别给予0（缺乏组；n = 40）、2（基础需求量组；对照组；n = 46）或8（补充组；n = 36）mg叶酸/千克饮食，持续32周。尸检时，识别出所有肉眼可见的结肠肿瘤，并进行组织学分类为发育异常或腺癌。叶酸补充组的高级别病变（高级别发育异常/原位癌和浸润性腺癌）发生率比对照组低46%（35.3%对65.1%，P = 0.009）。叶酸缺乏组的高级别病变发生率也比对照组低49%（33.3%对65.1%，P = 0.007）。与其他两组相比，叶酸缺乏组较高的死亡率（25%对6.5%和5.6%，P < 0.02）部分解释了该组高级别病变发生率较低的原因。这些数据表明，饮食中叶酸补充量为基础饮食需求量的4倍时，可显著抑制IL-2(null) x β2m(null)小鼠UC相关的结直肠癌发生。这些数据还表明，叶酸缺乏可能抑制慢性UC中的结直肠癌发生。然而，叶酸缺乏组观察到的高死亡率妨碍了就该模型中叶酸缺乏对UC相关结直肠癌发生的影响得出明确结论。
