What parts of our diet increase and decrease the risk of colorectal cancer?
Colorectal cancer is the 3rd most common cancer in the world and the 4th most common cancer in the UK. There is a huge genetic risk aspect but studies have found that CRC cancer risk is increased by red and processed meat and alcohol and that fibre and fruit and vegetables can help prevent and treat this cancer. Antioxidants such as vitamins A, C and E and minerals Zinc, Selenium and Copper, have also been found to have benefits as they neutralise reactive oxidative species (ROS) and associated risks of free radical DNA damage and cancer.
Cancer occurs when normal cell DNA mutates and is not repaired causing overproliferation of cells. This can occur in 3 stages, initiation (when a cell is exposed to a carcinogenic mutagen which damages DNA), promotion (when there is a lack of cell apoptosis and rapid cell proliferation and cell angiogenesis) and progression (when the cells spread to new tissues forming metastasis secondaries). The epidemiological EPIC (European prospective investigation into cancer and nutrition) prospective cohort study of 10 EU countries (so only westerners- a limitation of the study) and over half (Papadimitriou et al., 2022) a million people (a strength of the study-large cohort size), found that diet plays a vital role in the protection against cancer. It specifically found that exposure to acetaldehyde carcinogen from alcohol and processed red meat was positively associated with CRC. On the other hand, dairy, wholegrains and high fibre, fruit and vegetables were inversely associated with the risk of CRC.
Red meat has been shown to increase iron ferroptosis and increase the free radical release and DNA damage to colorectal cells in the large intestine. It is also high in saturated fat and the radioactive oxygen species (ROS) produced by red meat are said to cause lipid peroxidation and damage DNA, increasing cancer risk. Processed meat has also been found to contain lots of n-nitroso-compounds which damage DNA. These compounds are created when meat protein reacts with nitrites in additives such as sodium and potassium nitrites which are used to enhance shelf life and add flavour and colour in meat processing. It was found in the Cancer of Unknown Primary (CUP) 2011 metanalysis study of 21 prospective studies that red and processed meat cause a 14% increased risk RR: 1.14 (95% CI = 1.04–1.24) with a linear dose relationship RR for every 100g/day. This was a 17% increase, RR: 1.17, (95% CI = 1.05–1.31) for red meat with 100g/day dose risk increase and an 18% risk RR: 1.18, (95% CI = 1.10–1.28) increase for processed meat at a 50g/day risk dose relationship. This was supported by the World Cancer Research Fund report 1998 which found convincing evidence (this was later downgraded in the 2018 report to probable) evidence that red meat increased the risk of CRC by 1.16 (1.08–1.26 CL). The Larsson et al 2006 metanalysis study found that red meat increased the risk of CRC by 28% with processed meat increasing RR:1.20.
Alcohol has also been shown to increase the risk of CRC, with acetaldehyde a known carcinogen. Intestinal bacteria have been shown to oxidise ethanol leading to increased acetaldehyde and associated prostaglandins and radiative oxidative species (ROS) in the colon and lipid peroxidation, decreased mineral absorption and B9. Decreased folate is associated with increased mutation risk and decreased DNA repair. The World Cancer Research Fund (WCRF) found that 13 cohort and 14 case-control studies show an increased risk of CRC with acetaldehyde. RR:1.09 with a dosal relationship with every 10g alcohol/day and an effect more prominent in men than women (Demeyer et al., 2008). Alcohol is especially toxic as the liver focuses on the detoxification of ethanol over storage of sugars (increasing insulin resistance risk) and the production and storage of key minerals such as vitamins A, D, E, K and B12 and gut hormones. Alcohol compromises the liver, reducing its detoxification capacity, increasing the risk of toxic metabolites entering the tissue and damaging DNA and causing cancer.
Fibre and fruit and vegetables have been shown to have a protective influence on colorectal cancer. This is because fruit and vegetables tend to be rich in vitamins A, C and E which have antioxidative properties, and in B9 folate which is essential for DNA and RNA synthesis and repair and methylation and also in phytoestrogens, flavonoids, carotenoids, isothiocyanates and phytosterols all which have been shown to have anti-cancer properties. Flavonoids especially have been shown to reduce infection and help in the absorption of vitamin C and protection of vitamin C from oxidative damage, and Lycopene in tomatoes, Tannins in grapes, and Terpenes in citrus fruits (they give plants their fragrance), have been found to be anti-carcinogenic (Mileo et al., 2019). Despite this, the CUP 2007 report and WCRF 2007 reports found only limited evidence for the incidence reduction qualities of fruit and vegetables on CRC. Fibre has been hypothesised to reduce CRC risk by increasing stool weight and GI motility and decreasing the transit time of stool in the large intestine and reducing the contact time and dilution of carcinogens in the large intestine. Additionally, both insoluble fibre and soluble fibre fermentation products, small-chain fatty acids (SCFA) have been shown to help reduce cell overproliferation and induce cell death via apoptosis. They also are acidic and lower the pH of the colon and inhibit pro-carcinogenic bile acids (Jia et al., 2018). The Women’s Health Initiative RCT found no significant change in the incidence of CRC with fruit and vegetables RR:0.91 (0.82–1.01).
Overall, there is considerable evidence for the carcinogenic properties of sodium and potassium nitrites and high iron in red and processed meats and carcinogenic alcohol increase the risk of colorectal cancer. More research is needed to confirm the benefits of plants and fibre in reducing carcinogenic properties.
Copyright Laura Campbell 21/03/2023
References
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Jia, W., Xie, G., & Jia, W. (2018). Bile acid-microbiota crosstalk in gastrointestinal inflammation and carcinogenesis. Nat Rev Gastroenterol Hepatol, 15(2), 111–128. https://doi.org/10.1038/nrgastro.2017.119
Mileo, A. M., Nisticò, P., & Miccadei, S. (2019). Polyphenols: Immunomodulatory and Therapeutic Implication in Colorectal Cancer. Front Immunol, 10, 729. https://doi.org/10.3389/fimmu.2019.00729
Papadimitriou, N., Bouras, E., van den Brandt, P. A., Muller, D. C., Papadopoulou, A., Heath, A. K., Critselis, E., Gunter, M. J., Vineis, P., Ferrari, P., Weiderpass, E., Boeing, H., Bastide, N., Merritt, M. A., Lopez, D. S., Bergmann, M. M., Perez-Cornago, A., Schulze, M., Skeie, G., . . . Tsilidis, K. K. (2022). A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC. Clin Gastroenterol Hepatol, 20(4), 864–873.e813. https://doi.org/10.1016/j.cgh.2021.04.028
