Miller Eric A, Keku Temitope O, Satia Jessie A, Martin Christopher F, Galanko Joeseph A, Sandler Robert S
Department of Epidemiology, School of Public Health, University of North Carolina, Chapel Hill, NC 27599-7555, USA.
Cancer Epidemiol Biomarkers Prev. 2005 Feb;14(2):525-8. doi: 10.1158/1055-9965.EPI-04-0466.
Decreased apoptosis in the colon is potentially an early indicator of colon cancer risk and may be influenced by calcium and vitamin D. This report describes the associations of calcium intake and 25-hydroxyvitamin D levels with apoptosis in colorectal epithelium.
Consecutive patients undergoing colonoscopies were recruited for a study designed to examine risk and etiologic factors for colorectal adenomas. Diet was assessed by food frequency questionnaire, and in one subpopulation, serum 25-hydroxyvitamin D levels were measured using an enzyme immunoassay. Apoptosis was scored from normal rectal mucosal pinch biopsies. Linear and logistic regression analyses were used to examine associations between calcium, serum vitamin D, and apoptotic scores. Data were available for 498 and 280 patients for the calcium and vitamin D analyses, respectively.
Associations of calcium intake and vitamin D with apoptosis were modified by adenoma case-status. In an adjusted logistic regression model, patients with adenomas in the highest versus lowest tertile of dietary calcium intake had 3.4 times higher odds [95% confidence interval (CI), 0.9-12.9] of elevated apoptotic scores. In adenoma-free patients, high calcium intake was not related to apoptosis (OR, 1.2; 95% CI, 0.6-2.7). In contrast, the highest level of 25-hydroxyvitamin D was associated with higher apoptosis in adenoma-free patients (OR, 2.6; 95% CI, 1.1-6.2) and slightly lower levels in patients with adenomas (OR, 0.6; 95% CI, 0.2-2.2).
These results are consistent with a calcium and vitamin D-mediated apoptotic mechanism in colon carcinogenesis.
结肠细胞凋亡减少可能是结肠癌风险的早期指标，且可能受钙和维生素D的影响。本报告描述了钙摄入量和25-羟维生素D水平与结直肠上皮细胞凋亡之间的关联。
连续入选接受结肠镜检查的患者，进行一项旨在研究结直肠腺瘤风险和病因学因素的研究。通过食物频率问卷评估饮食情况，在一个亚组中，采用酶免疫测定法测量血清25-羟维生素D水平。从正常直肠黏膜钳取活检组织中对细胞凋亡进行评分。采用线性和逻辑回归分析来研究钙、血清维生素D与凋亡评分之间的关联。分别有498例和280例患者的数据可用于钙和维生素D分析。
钙摄入量和维生素D与细胞凋亡的关联因腺瘤病例状态而有所改变。在调整后的逻辑回归模型中，饮食钙摄入量处于最高三分位数与最低三分位数的腺瘤患者，其凋亡评分升高的几率高3.4倍[95%置信区间（CI），0.9 - 12.9]。在无腺瘤患者中，高钙摄入量与细胞凋亡无关（比值比，1.2；95% CI，0.6 - 2.7）。相比之下，25-羟维生素D的最高水平与无腺瘤患者较高的细胞凋亡相关（比值比，2.6；95% CI，1.1 - 6.2），而在腺瘤患者中水平略低（比值比，0.6；95% CI，0.2 - 2.2）。
这些结果与钙和维生素D介导的结肠癌发生凋亡机制一致。
