Mechanisms Linking Colorectal Cancer to the Consumption of (Processed) Red Meat: A Review

Abstract

Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the world. The vast majority of CRC cases have been linked to environmental causes rather than to heritable genetic changes. Over the last decades, epidemiological evidence linking the consumption of red and, more convincingly, of processed red meat to CRC has accumulated. In parallel, hypotheses on carcinogenic mechanisms underlying an association between CRC and the intake of red and processed red meat have been proposed and investigated in biological studies. The hypotheses that have received most attention until now include (1) the presence of polycyclic aromatic hydrocarbons and heterocyclic aromatic amines, two groups of compounds recognized as carcinogenic, (2) the enhancing effect of (nitrosyl)heme on the formation of carcinogenic N-nitroso compounds and lipid peroxidation. However, none of these hypotheses completely explains the link between red and processed red meat intake and the CRC risk. Consequently, scientists have proposed additional mechanisms or refined their hypotheses. This review first briefly summarizes the development of CRC followed by an indepth overview and critical discussion of the different potential carcinogenic mechanisms underlying the increased CRC risk associated with the consumption of red and processed red meat.

Dietary and Lifestyle Factors Associated with Colorectal Cancer Risk and Interactions with Microbiota: Fiber, Red or Processed Meat and Alcoholic Drinks

“…Generated secondary bile acids and end products of heme cause inflammation and cytotoxic effects, resulting in the formation of reactive nitrogen species/reactive oxygen species and cytokines, promoting epithelial cell hyperproliferation. Endogenous and exogenous N-nitroso compound production increases through adding nitrates and nitrites to processed meats, enhancing the cytotoxicity of nitrosyl heme and reactive chlorine species, which may offer part of the explanation for why processed meat has been associated more strongly with the risk of CRC [27] .…”

Dietary fruit, vegetable, fat and red and processed meat intakes and Barrett’s esophagus risk: a systematic review and meta-analysis

“…Recently, meats, particularly red and processed meat intakes, have been reported as risk factors for oral cavity and oropharynx cancer2829, EAC303132, gastric cancer3334, colorectal cancer353637, pancreatic cancer38, hepatocellular carcinoma39, breast cancer4041, lung cancer4243, renal cancer44, bladder cancer4546, ovarian cancer47, brain tumors48, glioma49, non-Hodgkin lymphoma50, type 2 diabetes51, stroke52 and coronary heart disease53. Red and processed meats are one of the major sources of nitrate and N-nitroso compounds, which are considered to be carcinogenic in humans and risk factors of BE54; however, it is worth mentioning that not all cooked meats increase BE risk.…”

Micronutrients: A Double-Edged Sword in Microbe-Induced Gastric Carcinogenesis

“…Similar to the associations observed in esophageal adenocarcinoma, positive associations between heme intake and gastric [8,10], as well as colorectal cancer [7,8,12–14], have also been demonstrated (Figure 1A, Key Figure). The mechanism by which heme iron increases cancer risk is likely linked to its ability to function as a nitrosylating agent, leading to formation of N-nitroso compounds that are known carcinogens [15]. Overall, existing data clearly indicate that heme is a significant risk factor for gastrointestinal carcinogenesis.…”