维生素D、补钙与结肠直肠腺瘤：一项随机试验的结果

Vitamin D, calcium supplementation, and colorectal adenomas: results of a randomized trial.

作者信息

Grau Maria V, Baron John A, Sandler Robert S, Haile Robert W, Beach Michael L, Church Timothy R, Heber David

机构信息

Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, NH, USA.

出版信息

J Natl Cancer Inst. 2003 Dec 3;95(23):1765-71. doi: 10.1093/jnci/djg110.

DOI:10.1093/jnci/djg110

PMID:14652238

Abstract

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.

摘要

背景

钙和维生素D似乎都对大肠有抗肿瘤作用。尽管这些营养素在骨骼和正常肠道中代谢相互关联，但它们在大肠癌发生过程中的潜在相互作用尚不清楚。

方法

在一项预防结直肠腺瘤复发的多中心、安慰剂对照的钙补充剂随机临床试验中，我们评估了803名受试者中补充钙和维生素D状态对腺瘤复发的独立和联合作用。测定血清25-羟[25-(OH)]维生素D和1,25-二羟[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）基因中的Taq I和Fok I多态性。计算血清维生素D水平定义的组内补充钙以及治疗组内血清维生素D水平与任何腺瘤复发的风险比（RRs）。还评估了VDR多态性与复发风险的关联。所有统计检验均为双侧检验。

结果

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，补充钙与腺瘤复发无关，而在水平高于中位数的受试者中，补充钙与风险降低相关（RR = 0.71，95%置信区间[CI] = 0.57至0.89，交互作用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，交互作用P = 0.006）。VDR多态性与腺瘤复发无关，也未改变与维生素D或钙的关联。