Colorectal cancer (CRC) is one of the major tumor entities worldwide, with an increasing incidence in younger people. CRC formation is causally linked to various genetic, life-style and dietary risk factors. Among the ladder, the consumption of red meat has emerged as important risk factor contributing to CRC. A large body of evidence shows that heme iron is the critical component of red meat, which promotes colorectal carcinogenesis. In this review, we describe the uptake and cellular fate of both heme and inorganic iron in intestinal epithelial cells. Next, an overview on the DNA damaging properties of heme iron is provided, highlighting the DNA adducts relevant for CRC etiology. Moreover, heme triggered mechanisms leading to colonic hyperproliferation are presented, which are intimately linked to changes in the intestinal microbiota induced by heme. A special focus was set on the impact of heme iron on innate and adaptive immune cells, which could be relevant in the context of CRC. Finally, we recapitulate in vivo studies providing evidence for the tumor-promoting potential of dietary heme iron. Altogether, heme iron affects numerous key pathways involved in the pathogenesis of CRC.

中文翻译：

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红肉中血红素铁引发大肠癌发生的机理。

大肠癌（CRC）是全球主要的肿瘤实体之一，在年轻人中发病率不断上升。CRC形成与各种遗传，生活方式和饮食风险因素有因果关系。在阶梯中，食用红肉已成为导致CRC的重要危险因素。大量证据表明，血红素铁是红肉的关键成分，它促进结直肠癌变。在这篇综述中，我们描述了血红素和无机铁在肠上皮细胞中的摄取和细胞命运。接下来，概述了血红素铁的DNA损伤特性，重点介绍了与CRC病因有关的DNA加合物。此外，还提出了血红素触发的导致结肠过度增殖的机制，它们与血红素诱导的肠道菌群变化密切相关。特别关注血红素铁对先天和适应性免疫细胞的影响，这可能与CRC有关。最后，我们总结了体内研究，为膳食血红素铁的促肿瘤潜力提供了证据。总的来说，血红素铁影响CRC发病机理中涉及的许多关键途径。