Vitamin D, calcium supplementation, and colorectal adenomas: Results of a randomized trial
Vitamin D, calcium supplementation, and colorectal adenomas: Results of a randomized trial
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DOI：
10.1093/jnci/djg110
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发表时间：
2003-12-03
期刊：
影响因子：
--
通讯作者：
Heber, D
中科院分区：
文献类型：
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作者：
Grau, MV;Baron, JA;Heber, D
背景：钙和维生素D似乎都对大肠有抑制作用。虽然这些营养物质在骨骼和正常肠道中的代谢是相互关联的，但它们在大肠癌发生中的潜在相互作用还没有得到很好的理解。研究方法：我们在一项多中心、安慰剂对照、随机临床试验中评估了补钙和维生素D状态对803例受试者腺瘤复发的独立和联合作用，该试验旨在研究补钙预防结直肠腺瘤复发。测定血清25-羟基[25-（OH）]维生素D和1，25-二羟基[1，25（OH）（2）]维生素D水平，并通过聚合酶链反应分析维生素D受体（VDR）基因的Taq I和Fok I多态性。根据血清维生素D水平和治疗组血清维生素D水平计算任何腺瘤复发的风险比（RR）。VDR多态性与复发风险的关系也被评估。所有统计检验均为双侧检验。结果如下：在基线25-（OH）维生素D水平等于或低于中位数（29.1 ng/mL）的受试者中，钙补充与腺瘤复发无关，而在水平高于中位数的受试者中，钙补充与风险降低相关（RR = 0.71，95%置信区间[CI] = 0.57至0.89，相互作用P = 0.012）。相反，血清25-（OH）维生素D水平仅在接受钙补充剂的受试者中与风险降低相关（维生素D每增加12 ng/mL的RR = 0.88，95% CI = 0.77至0.99，相互作用P = 0.006）。VDR多态性与腺瘤复发无关，也没有改变与维生素D或钙的相关性。结论：钙补充和维生素D状态似乎在很大程度上共同作用，而不是单独作用，以降低结直肠腺瘤复发的风险。VDR基因型似乎与风险无关。
Background: Calcium and vitamin D both appear to have antineoplastic effects in the large bowel. Although these nutrients are inter-related metabolically in bone and in the normal intestine, their potential interactions in large-bowel carcinogenesis are not well understood. Methods: We assessed independent and joint effects of calcium supplementation and vitamin D status on adenoma recurrence in 803 subjects in a multi-center, placebo-controlled randomized clinical trial of calcium supplementation for the prevention of colorectal adenoma recurrence. Serum levels of 25-hydroxy [25-(OH)] vitamin D and 1,25-dihydroxy [1,25(OH)(2)] vitamin D levels were determined, and the Taq I and Fok I polymorphisms in the vitamin D receptor (VDR) gene were analyzed by polymerase chain reaction. Risk ratios (RRs) for any adenoma recurrence were computed for calcium supplementation within groups defined by serum vitamin D levels and for serum vitamin D levels within treatment groups. Associations of VDR polymorphisms with recurrence risk were also evaluated. All statistical tests were two-sided. Results: Among subjects with baseline 25-(OH) vitamin D levels at or below the median (29.1 ng/mL), calcium supplementation was not associated with adenoma recurrence, whereas among those with levels above the median, calcium supplementation was associated with a reduced risk (RR = 0.71, 95 % confidence interval [CI] = 0.57 to 0.89, P for interaction = .012). Conversely, serum 25-(OH) vitamin D levels were associated with a reduced risk only among subjects receiving calcium supplements (RR per 12 ng/mL increase of vitamin D = 0.88, 95% CI = 0.77 to 0.99, P for interaction = .006). VDR polymorphisms were not related to adenoma recurrence and did not modify the associations with vitamin D or calcium. Conclusions: Calcium supplementation and vitamin D status appear to act largely together, not separately, to reduce the risk of colorectal adenoma recurrence. VDR genotype does not appear to be associated with risk.