Supplemental calcium and vitamin D reduce indicators of cancer-promoting inflammation in normal colorectal tissue in humans, thus furthering our understanding of how they may help prevent colorectal cancer. Increased COX-2 and decreased 15-hydroxyprostaglandin dehydrogenase (15-HPGD) expression promote prostaglandin-mediated inflammation and colorectal carcinogenesis. Experimental studies suggest that vitamin D and calcium may inhibit these pathways, but their effects on colorectal tissue COX-2 and 15-HPGD expression in humans are unknown. We tested the effects of supplemental vitamin D (1,000 IU/day) and/or calcium (1,200 mg/day) on COX-2 and 15-HPGD expression in the morphologically normal rectal mucosa from 62 paients with colorectal adenoma in a placebo-controlled chemoprevention trial. We measured biomarker expression using automated IHC and quantitative image analysis at baseline and 1-year follow-up, and assessed treatment effects using mixed linear models. The primary outcome was the COX-2/15-HPGD expression ratio, because these enzymes function as physiologic antagonists. After 1 year of treatment, the mean COX-2/15-HPGD expression ratio in full-length crypts proportionately decreased 47% in the vitamin D group (P = 0.001), 46% in the calcium group (P = 0.002), and 34% in the calcium + vitamin D group (P = 0.03), relative to the placebo group. Among individuals with the functional vitamin D–binding protein isoform DBP2 (GC rs4588*A), the COX-2/15-HPDG ratio decreased 70% (P = 0.0006), 75% (P = 0.0002), and 60% (P = 0.006) in the vitamin D, calcium, and combined supplementation groups, respectively, relative to placebo. These results show that vitamin D and calcium favorably modulate the balance of expression of COX-2 and 15-HPGD—biomarkers of inflammation that are strongly linked to colorectal carcinogenesis—in the normal-appearing colorectal mucosa of patients with colorectal adenoma (perhaps especially those with the DBP2 isoform). Prevention Relevance: Supplemental calcium and vitamin D reduce indicators of cancer-promoting inflammation in normal colorectal tissue in humans, thus furthering our understanding of how they may help prevent colorectal cancer.

中文翻译：

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临床试验中维生素 D 和钙对结直肠腺瘤患者形态正常的结直肠粘膜的炎症调节

补充钙和维生素 D 可减少人类正常结直肠组织中促癌炎症的指标，从而加深我们对它们如何帮助预防结直肠癌的理解。增加的 COX-2 和减少的 15-羟基前列腺素脱氢酶 (15-HPGD) 表达促进前列腺素介导的炎症和结直肠癌的发生。实验研究表明，维生素 D 和钙可能会抑制这些途径，但它们对人类结直肠组织 COX-2 和 15-HPGD 表达的影响尚不清楚。我们测试了补充维生素 D（1,000 IU/天）和/或钙（1,200 mg/天）对 62 名结直肠腺瘤患者在安慰剂对照下形态正常的直肠粘膜中 COX-2 和 15-HPGD 表达的影响化学预防试验。我们在基线和 1 年随访时使用自动 IHC 和定量图像分析测量生物标志物表达，并使用混合线性模型评估治疗效果。主要结果是 COX-2/15-HPGD 表达比率，因为这些酶起着生理拮抗剂的作用。治疗 1 年后，全长隐窝中的平均 COX-2/15-HPGD 表达比率在维生素 D 组中按比例下降 47% (P = 0.001)，在钙组中下降 46% (P = 0.002)，并且相对于安慰剂组，钙 + 维生素 D 组为 34% (P = 0.03)。在具有功能性维生素 D 结合蛋白亚型 DBP2 (GC rs4588*A) 的个体中，COX-2/15-HPDG 比率降低了 70% (P = 0.0006)、75% (P = 0.0002) 和 60% (P = 0.006) 在维生素 D、钙和联合补充组中，分别相对于安慰剂。这些结果表明，维生素 D 和钙有利于调节 COX-2 和 15-HPGD（与结直肠癌发生密切相关的炎症生物标志物）在结直肠腺瘤患者（可能尤其是那些与 DBP2 亚型）。预防相关性：补充钙和维生素 D 可减少人体正常结直肠组织中促癌炎症的指标，从而加深我们对它们如何帮助预防结直肠癌的理解。