*2.3.1 Mechanism*

Red meat consists of compounds such as haem iron (HI) that facilitates the endogenous formation of N-nitroso compounds (NOCs) such as nitrosylated HI, catalyzing its formation from natural precursors in the gastrointestinal tract (GI), as well as through lipid peroxidation in the GI [4, 24, 25]. In addition, HI can induce oxidative stress, colonocyte proliferation through the lipid-peroxidation pathway, and production of free radicals in the colonic stream [25]. The carcinogenic compounds forming during processing and cooking include NOCs and polycyclic aromatic hydrocarbons (PAHs) [25]. Cooking red or processed meat at high temperatures produces mutagens such as PAHs and heterocyclic aromatic amine (HAAs) [4, 25], both of which have been linked to CRC development in experimental studies [26]. The latter are genotoxic, and the extent to which HAAs' conversion to genotoxic metabolites occurs as a result of amino acids and creatinine reacting at high cooking temperatures is higher in humans than experimental animals. HAAs become DNA-alkylating agents, inducing DNA mutations after activation by various metabolizing enzymes. The GI microbiota adapts to meat intake and HAAs, resulting in HAAs possibly becoming more genotoxic in those with a high meat intake. However, the majority of studies that have investigated meat and phenotype interactions did not yield convincing evidence. It is therefore probable though that heat-induced mutagens found on the surface of well-done red meat can cause colon cancer in those with a genetic predisposition. NOCs, PAHs, and HAAs are considered to be genotoxic by acting directly on DNA, causing point mutations, deletions, and insertions. However, there is little direct evidence that these mechanisms come into play following meat consumption. A high consumption of HI (excluding other forms of iron), NOCs, HAAs, and PAHs has been associated with an increased risk of colorectal tumors, with a few exceptions. Genetic variations in NOCs' and HAAs' metabolism may alter the relationship between the consumption of red meat and the risk of developing colon cancer. However, there is substantial supporting mechanistic evidence regarding HI, NOCs, and HAAs being involved in colon carcinogenesis. A high consumption of red meat (300–420 g/day), increased levels of DNA adducts, is presumed to be derived from NOCs, in exfoliated colonocytes or rectal biopsies [25].

**13**

*Effectivity and Modulating Pathways for the Prevention of Colorectal Cancer: Diet, Body Fatness…*

There is strong convincing evidence that consuming processed meat, i.e., meats preserved by smoking, curing, or salting, or addition of chemical preservatives, increases the risk of CRC [7, 8]. The evidence is generally consistent by showing an increased risk of CRC with increased consumption of processed meat. The doseresponse meta-analysis showed a significant increased risk of CRC at consumption

The carcinogenic compounds that form during processing include NOCs and PAHs. NOCs are exogenously introduced from nitrates and nitrites added during the preservation process [25, 27] but can also be formed endogenously. In processed meat, HI is nitrosylated because curing salt contains nitrate or nitrite. There is evidence that nitrosylated HI promotes carcinogenesis at doses that are five to six

However, it is likely that a combination of mechanisms contribute to a higher risk of developing CRC among those who consume high quantities of processed meat. Similar to red meat, processed meat is high in fat, protein, and HI, which can promote carcinogenesis through the mechanisms described under red meat [25, 26]. In addition, processed meats such as sausages are often cooked at high temperatures, leading to increased exposure to HAAs and PAHs [25, 27], with levels varying according to meat type, temperature, cooking time, and method [25]. The invariably higher fat content of processed meat when compared to red meat may stimulate carcinogenesis through synthesis of secondary bile acids. However, human data

A dose-response meta-analysis showed no significant association between fruit consumption and CRC. There was evidence of a nonlinear dose response of CRC and fruit intake showing a significant increased risk at low levels (less than 100 g per day) of intake [7, 8]. Hence there is limited suggestive evidence available that a

Apart from fiber content, fruits are a rich source of vitamins C and E, as well as numerous bioactive compounds which may have an anticarcinogenic potential. These include folate, flavonoids, polyphenols, and limonene [4, 28]. Many of these compounds have potent anti-oxidative properties which could inhibit cellular dam-

Based on epidemiological studies, the term vegetables may cover different categories, namely, total vegetables (non-starchy vegetables and starchy vegetables), non-starchy vegetables, fresh vegetables (as opposed to preserved vegetables), and raw vegetables (excluding cooked vegetables) [7]. There is limited suggestive evidence that a low intake (less than 100 g per day) of cruciferous vegetables and non-starchy vegetables might increase the risk of CRC [7, 8]. However, there is also limited evidence that a high intake of fruits and vegetables protects against

*DOI: http://dx.doi.org/10.5772/intechopen.84764*

times lower than non-nitrosylated HI [25].

supporting this hypothesis are weak [27].

low consumption of fruit increases the risk of colorectal [8].

age and exposure to reactive oxygen species [28].

**2.4 Processed meat**

levels of 50 g/day [8].

*2.4.1 Mechanism*

**2.5 Fruits**

*2.5.1 Mechanism*

**2.6 Non-starchy vegetables**

*Effectivity and Modulating Pathways for the Prevention of Colorectal Cancer: Diet, Body Fatness… DOI: http://dx.doi.org/10.5772/intechopen.84764*
