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.