Bostick R M, Boldt M, Darif M, Wood J R, Overn P, Potter J D
Department of Public Health Sciences-Epidemiology, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina 27157, USA.
Cancer Epidemiol Biomarkers Prev. 1997 Dec;6(12):1021-7.
In persons at higher risk for colon cancer (e.g., those with sporadic adenoma or ulcerative colitis), compared to those at lower risk, colonic epithelial cell proliferation kinetics are altered. We have shown previously that calcium supplementation appears to normalize the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients. In a pilot randomized, double-blind, placebo-controlled, clinical trial conducted concurrently with our previously published sporadic adenoma trial, we tested whether calcium supplementation can also modulate cell proliferation kinetics in patients with ulcerative colitis. Ulcerative colitis patients (n = 31) were randomized to placebo or 2.0 g of supplemental calcium daily. Colorectal epithelial cell proliferation was determined by immunohistochemical detection of proliferating cell nuclear antigen labeling of cells in "nonprep" rectal biopsies taken at randomization and after 2 months treatment. All biopsies were scored by one reviewer. Differences in mean follow-up minus baseline labeling index (LI; the proportion of colon crypt epithelial cells that were labeled) and in the phi(h) (proportion of labeled cells that were in the upper 40% of the crypts) were compared with analysis of covariance. Pill-taking adherence was 97%. Biopsy-scoring reliability was high (r = 0.89). The pooled baseline LI and phi(h) were 6.3% and 5.6%, respectively. The LI in the calcium group decreased by 0.5% (proportionately, 3%) more than in the placebo group (P = 0.91). Similarly, the phi(h) in the calcium group decreased by 0.3% (proportionately, 10%) more than in the placebo group (P = 0.85). This pilot study does not suggest that 2.0 g of calcium as calcium carbonate daily can substantially normalize either the rate or distribution of proliferating cells over a 2-month period in the colon crypts of patients with ulcerative colitis; a more definitive answer to the question of whether calcium may be effective would require a study with a larger sample size and/or other study design modifications.
与患结肠癌风险较低的人群相比，结肠癌高危人群（如散发性腺瘤或溃疡性结肠炎患者）的结肠上皮细胞增殖动力学发生了改变。我们之前已经表明，补充钙似乎能使增殖细胞的分布正常化，而不影响散发性腺瘤患者结直肠黏膜的增殖速率。在一项与我们之前发表的散发性腺瘤试验同时进行的初步随机、双盲、安慰剂对照临床试验中，我们测试了补充钙是否也能调节溃疡性结肠炎患者的细胞增殖动力学。溃疡性结肠炎患者（n = 31）被随机分为安慰剂组或每日补充2.0 g钙组。通过免疫组织化学检测随机分组时及治疗2个月后采集的“未预处理”直肠活检组织中细胞的增殖细胞核抗原标记，来确定结直肠上皮细胞增殖情况。所有活检组织均由一名评估者评分。采用协方差分析比较平均随访时减去基线标记指数（LI；标记的结肠隐窝上皮细胞比例）和phi(h)（标记细胞在隐窝上部40%中的比例）的差异。服药依从性为97%。活检评分可靠性高（r = 0.89）。合并的基线LI和phi(h)分别为6.3%和5.6%。钙组的LI比安慰剂组降低了0.5%（按比例为3%）（P = 0.91）。同样，钙组的phi(h)比安慰剂组降低了0.3%（按比例为10%）（P = 0.85）。这项初步研究并不表明，每日2.0 g碳酸钙形式的钙在2个月内能够使溃疡性结肠炎患者结肠隐窝中增殖细胞的速率或分布基本正常化；关于钙是否有效的问题，更确切的答案需要样本量更大和/或其他研究设计改进的研究来给出。
