低钙摄入与结直肠癌:机制整合、异质性与精准预防

马风兰; 马红; 赵越

doi:10.16689/j.cnki.cn11-9349/r.2026.04.017

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肿瘤代谢与营养电子杂志 ›› 2026, Vol. 13 ›› Issue (4) : 576-581. DOI: 10.16689/j.cnki.cn11-9349/r.2026.04.017

综述

低钙摄入与结直肠癌:机制整合、异质性与精准预防

¹马风兰, ¹马红, ²赵越

作者信息 +

Low calcium intake and colorectal cancer: Mechanistic integration, heterogeneity, and precision prevention

¹Ma Fenglan, ¹Ma Hong, ²Zhao Yue

Author information +

文章历史 +

摘要

结直肠癌(CRC)是全球高发恶性肿瘤。流行病学研究一致表明膳食钙摄入与CRC风险呈负相关,但多项随机对照试验(RCT)未能证实补钙的获益,形成“临床悖论”。本文以该悖论为切入点,构建低钙致CRC的“四层级联”体系:管腔层面,低钙削弱钙离子对胆汁酸及游离脂肪酸的螯合解毒,导致肠黏膜屏障损伤;分子层面,低钙使钙敏感受体(CaSR)静息,解除其对Wnt/β-catenin的双重负调控;协同层面,维生素D受体(VDR)轴与CaSR形成双向正反馈环路,低钙与低维生素D“双向锁定”放大抑癌信号丧失;菌群层面,肠道菌群失调通过代谢产物反向加剧前三层损伤,形成恶性闭环。基于该体系,本文系统分析维生素D状态、CaSR基因型、菌群代谢负荷三个异质性来源对钙效应的修饰作用,从而解释RCT结果不一致的潜在原因,并提炼出四项可检验的假设,为CRC的精准预防提供整合性理论依据与可验证方向。

Abstract

CRC is one of the most common and highly lethal malignancies worldwide. Epidemiological studies consistently demonstrate an inverse association between dietary calcium intake and CRC risk; however, several RCTs have failed to confirm a protective effect of calcium supplementation, giving rise to a “clinical paradox.” Taking this paradox as a starting point, this article proposes a “four-level cascade” framework linking low calcium intake to CRC pathogenesis: at the luminal level, low calcium weakens the chelation and detoxification of bile acids and free fatty acids, leading to damage to the intestinal mucosal barrier; at the molecular level, low calcium inactivates the CaSR, relieving its dual negative regulation of the Wnt/β-catenin pathway; at the synergistic level, the vitamin D-VDR axis and CaSR form a bidirectional positive feedback loop, and low calcium and low vitamin D create a “bidirectional lock” effect that amplifies the loss of tumor suppressor signals; at the microbiota level, gut dysbiosis and its metabolic byproducts reciprocally exacerbate the damage to the previous three layers, forming a vicious cycle. Based on this integrative framework, this article systematically examines how three sources of heterogeneity—vitamin D status, CaSR genotype, and microbial metabolic load—modify calcium signaling, thereby providing a plausible explanation for the inconsistent results of RCTs. Finally, we distill four testable hypotheses, offering an integrated theoretical foundation and verifiable directions for the precision prevention of CRC.

导出引用

马风兰, 马红, 赵越. 低钙摄入与结直肠癌:机制整合、异质性与精准预防[J]. 肿瘤代谢与营养电子杂志. 2026, 13(4): 576-581 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.04.017

Ma Fenglan, Ma Hong, Zhao Yue. Low calcium intake and colorectal cancer: Mechanistic integration, heterogeneity, and precision prevention[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2026, 13(4): 576-581 https://doi.org/10.16689/j.cnki.cn11-9349/r.2026.04.017

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