Background & Aims

The effects of vitamin D on risk of colorectal cancer precursors are not clear. We examined the influence of vitamin D supplementation on risk of colorectal adenomas and serrated polyps in a prespecified ancillary study of a large-scale prevention trial (the vitamin D and omegA-3 trial, VITAL) of individuals who were free of cancer and cardiovascular disease at enrollment.

Methods

In VITAL trial, 25,871 adults with no history of cancer or cardiovascular disease (12,786 men 50 years or older and 13,085 women 55 years or older) were randomly assigned to groups given daily dietary supplements (2000 IU vitamin D₃ and 1 g marine n-3 fatty acid) or placebo. Patients were assigned to groups from November 2011 through March 2014 and the study ended on December 31, 2017. We confirmed conventional adenomas and serrated polyps by reviewing histopathology reports from participants who had reported a diagnosis of polyps and were asked by their doctors to return for a repeat colonoscopy or sigmoidoscopy in 5 years or less. We calculated the odds ratios (ORs) and 95% CIs by logistic regression, after adjusting for age, sex, n-3 treatment assignment, and history of endoscopy at time of randomization.

Results

During a median follow-up of 5.3 years, we documented 308 cases of conventional adenomas in 12,927 participants in the vitamin D group and 287 cases in 12,944 participants in the placebo group (OR for the association of vitamin D supplementation with adenoma, 1.08; 95% CI, 0.92–1.27). There were 172 cases of serrated polyps in the vitamin D group and 169 cases in the placebo group (OR for the association of vitamin D supplementation with serrated polyp, 1.02; 95% CI, 0.82–1.26). Supplementation was not associated with polyp size, location, multiplicity, or histologic features. We found evidence for an interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D, measured in 15,787 participants at randomization. Among individuals with serum levels of 25-hydroxyvitamin D below 30 ng/mL, the OR associated with supplementation for conventional adenoma was 0.82 (95% CI, 0.60–1.13), whereas among individuals with serum levels of 25-hydroxyvitamin D above 30 ng/mL, the OR for conventional adenoma was 1.20 (95% CI, 0.92–1.55) (P for interaction = .07). There was a significant interaction between vitamin D supplementation and serum level of 25-hydroxyvitamin D in their association with advanced adenoma (P for interaction = .04).

Conclusions

Based on an ancillary study of data from the VITAL trial, daily vitamin D supplementation (2000 IU) was not associated with risk of colorectal cancer precursors in average-risk adults not selected for vitamin D insufficiency. A potential benefit for individuals with low baseline level of vitamin D requires further investigation. ClinicalTrials.gov number: NCT01169259.

中文翻译：

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在一项随机试验中，维生素 D 补充剂与结直肠腺瘤或锯齿状息肉的风险之间没有关联。

背景与目标

维生素 D 对结直肠癌前体风险的影响尚不清楚。我们在一项针对未患癌症和心血管疾病的个体进行的大规模预防试验（维生素 D 和 omegA-3 试验，VITAL）的预先指定辅助研究中，检查了补充维生素 D 对结直肠腺瘤和锯齿状息肉风险的影响在入学时。

方法

在 VITAL 试验中，25,871 名没有癌症或心血管疾病病史的成年人（12,786 名 50 岁或以上的男性和 13,085 名 55 岁或以上的女性）被随机分配到每日膳食补充剂组（2000 IU 维生素 D ₃和 1 g 海洋 n- 3 脂肪酸）或安慰剂。患者被分配到 2011 年 11 月至 2014 年 3 月的组中，研究于 2017 年 12 月 31 日结束。我们通过审查报告诊断为息肉并被医生要求返回治疗的参与者的组织病理学报告，确认了常规腺瘤和锯齿状息肉。在 5 年或更短时间内重复结肠镜检查或乙状结肠镜检查。在调整了随机分组时的年龄、性别、n-3 治疗分配和内镜检查史后，我们通过逻辑回归计算了优势比 (OR) 和 95% CI。

结果

在 5.3 年的中位随访期间，我们记录了维生素 D 组 12,927 名参与者中的 308 例常规腺瘤和安慰剂组 12,944 名参与者中的 287 例（或维生素 D 补充与腺瘤的关联，1.08；95 % CI，0.92–1.27)。维生素 D 组有 172 例锯齿状息肉，安慰剂组有 169 例（补充维生素 D 与锯齿状息肉的相关性 OR，1.02；95% CI，0.82-1.26）。补充与息肉大小、位置、多样性或组织学特征无关。我们发现了维生素 D 补充剂与血清 25-羟基维生素 D 水平之间相互作用的证据，该证据在随机分组的 15,787 名参与者中进行了测量。在血清 25-羟基维生素 D 水平低于 30 ng/mL 的个体中，交互作用的P = .07)。补充维生素 D 与血清 25-羟基维生素 D 水平与晚期腺瘤之间存在显着交互作用（交互作用P = .04）。

结论

根据对 VITAL 试验数据的辅助研究，每日补充维生素 D (2000 IU) 与未选择维生素 D 不足的平均风险成人的结肠直肠癌前体风险无关。对维生素 D 基线水平低的个体的潜在益处需要进一步研究。ClinicalTrials.gov 编号：NCT01169259。