Diet and cancer

Diet and cancer are associated. While it is not yet possible to provide quantitative estimates of the overall risks, it has been estimated that 35 percent of cancer deaths may be related to dietary factors.^[1] Almost all cancers (80–90%) are caused by environmental factors,^[2] and of these, 30–40% of cancers are directly linked to the diet.^[3] Studies conducted over the years have show a strong correlation between diet and cancer. A comprehensive worldwide report Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective compiled by World Cancer Research Fund and American Institute for Cancer Research reports that there is significant relation between lifestyle (including food consumption) and cancer prevention. The same report recommends eating mostly foods of plant origin and aiming to meet nutritional needs through diet alone, while limiting consumption of cholesterol-dense foods, red meat, alcoholic drinks and salt, and avoiding sugary drinks and processed meat.

Nutrients in food

Nutrients in our food can fight cancer by protecting our bodies' cells from mutations caused mainly by carcinogens and free radicals. Antioxidants have been shown to minimize the damaging effects of free radicals^[4] and fight off tumors.^[5] Free radicals cause oxidative damage to DNA and mutate cells, which then proliferate into a tumor and thus cause cancer. The oxidative damage can be prevented when nutrients bind the free oxygen, therefore prohibiting it from roaming the body and damaging cells.

In addition to antioxidants, vitamins and trace minerals have a powerful effect on free radicals in terms of neutralizing them, as previously described, and preventing damage to the body's cells.^[6]

Importance of the whole food

Although many foods with certain nutrients have been demonstrated to be as effective in fighting off cancer, isolated consumption of these elements does not seem to confer the same benefits. Several studies have found that when isolating the nutrients by extracting it from the food source it is naturally found in, no benefits regarding cancer prevention were found.^[7] However, when increased amounts of the whole food were used, cancers were limited.

Fruits and vegetables

Fresh or frozen fruits and vegetables are both good, and contrary to common thought, frozen produce is just as nutrient dense as fresh produce, while dried produce is often sweetened, causing some of the nutrients to be broken down. Studies have shown produce consumption is effective in reducing cancers, especially in the gastrointestinal tract, lowering cancer rates by 22% and mortality to dietary related cancer by 11%.^[8] Berries have been causing a lot of commotion and promise in the world of cancer research. The darker the berry, the better in terms of being more packed with nutrients that is better at warding off cancer. Research has been putting the spot light on black raspberries and their ability to reduce oxidative stress and gastroesophageal reflux disease, each of which causes damage to the esophageal cells.^[9] Close runner-ups to the black raspberry are blueberries, blackberries, strawberries, and cranberries. These berries are high in vitamin C, fiber, and ellagic acid, which can prevent skin cancer.^[4] In addition to these nutrients, the American Association for Cancer Research found that berries are extremely high in polyphenol phytochemicals, and some research is suggesting that these phytochemicals are what is inhibiting tumor growth, more so than vitamins and minerals. These phytochemicals have the ability to interfere with tumor development, probably due to their natural job of protecting plants and their structures, as well as maintaining their vibrant colors (2007). Beta-carotene and lycopene are two prevalent nutrients that have shown a lot of promise in their capabilities to slow tumor growth.^[6]

Flavonoids

^[2] Flavonoids and catechins are nutrients that give foods a bitter taste, but they also are emerging as great anticancer agents. After looking into these nutrients further, Abdulla et al. found the best sources to be green and black teas, chocolate, wine, and grapes (2000). He also found that catechins are a powerful form of antioxidant that act as a powerful inhibitor of cancer growth. In fact, catechins are 100 times more powerful than vitamin C and 25 times more powerful than vitamin E in their antioxidant/growth inhibitor powers. The flavonoids and catechins together have proven the ability to protect cells from x-ray damage, block the progression of the cell cycle, and inhibit mutations (2000). Other foods high in flavonoids are garlic, onions, shallots, and leeks, which also contain vitamin C, selenium, and sulfur compounds that together, increase the metabolic disposal of chemical carcinogens,^[2] thus lowering the risk of cells turning cancerous.

Probiotics

Probiotics are bacteria that live in our gastrointestional tract and aid us in digestion as well as provide other benefits for its host. Ruize suggests that one of these benefits is their ability to eliminate procarcinogenic substances before they can turn carcinogenic. The probiotics are capable of altering certain enzymes (such as b-glucuronidase and nitro-reductase) that turn procarcinogens into carcinogenic agents by neutralizing the bad bacteria enzymes. Essentially, the good bacteria is cleansing the GI tract of harmful substances, such as poisonous bacteria and extraneous pollutants, found in the environment and our food chain. Without the probiotics, the immune system would be left to clean the body alone, causing a work overload and probably not as thorough, thus the probiotics are good because they help the immune system to keep toxins out of our intestines.^[10]

Reducing-risk factors

Increasing evidence suggests that diets high in foods containing fibre (or fiber) are associated with a reduced risk for cancer, especially cancer of the colon.^[11]

A few studies have also shown a reduced risk for cancers of the breast, rectum, oral cavity, pharynx, stomach, and other sites with diets rich in fruits, vegetables and grain products.^[12] Numerous studies have found evidence that carotenoids reduce the risk of some cancers. The evidence is particularly strong for lung cancer,^[13] even after taking smoking into account. Vitamin C is found in fruits, particularly citrus fruits and juices, and in green vegetables, as well as in some fortified foods. Of a group of epidemiologic studies investigating the role of vitamin C, three-quarters found that vitamin C, or fruit rich in vitamin C, provides significant protection.^[14]

A leaner diet is believed to lower cancer risk. Tomatoes, calcium, agaricus blazei mushrooms [1], other minerals, saponins, sausage tree, sea mat, cat's claw, and licorice are believed to prevent or suppress different kinds of cancerous tumors.^{[citation needed]} Currently there is not enough evidence for using mushrooms or mushroom extracts in the treatment of cancer, but there is significant potential for research in the area and future clinical trials, due to the numerous scientific studies which have shown they may offer a beneficial effect.^[15]

Mushrooms

Main article: Medicinal mushrooms

Main article: Polysaccharide-K

Some mushrooms offer an anti-cancer effect, which is thought to be linked to their ability to up-regulate the immune system. Some mushrooms known for this effect include, Reishi,^[16][17] Agaricus blazei, [2], Maitake,^[18] and Trametes versicolor.^[19] Research suggests the compounds in medicinal mushrooms most responsible for up-regulating the immune system and providing an anti-cancer effect, are a diverse collection of polysaccharide compounds, particularly beta-glucans. Beta-glucans are known as "biological response modifiers", and their ability to activate the immune system is well documented. Specifically, beta-glucans stimulate the innate branch of the immune system. Research has shown beta-glucans have the ability to stimulate macrophage, NK cells, T cells, and immune system cytokines. The mechanisms in which beta-glucans stimulate the immune system is only partially understood. One mechanism in which beta-glucans are able to activate the immune system, is by interacting with the Macrophage-1 antigen (CD18) receptor on immune cells.^[20]

A highly purified compound isolated from the medicinal mushroom Trametes versicolor, known as Polysaccharide-K, has become incorporated into the health care system of a few countries, such as Japan.^[21] Japan's Ministry of Health, Labour and Welfare approved the use of Polysaccharide-K in the 1980s, to stimulate the immune systems of patients undergoing chemotherapy.

Risk factors

Alcohol

Main articles: Alcohol and cancer and Alcohol and breast cancer

Alcohol is a risk factor for cancers of the mouth, esophagus, pharynx, and larynx, breast cancer, colorectal cancer, and liver cancer.

Contrary evidence

More recent studies have cast doubt on the claim that dietary fiber reduces the risk of colon cancer.^[22][23] Regarding prostate cancer, a major 2002 study concluded that "A low-fat, high-fiber diet heavy in fruits and vegetables has no impact on PSA levels in men over a four-year period, and does not affect the incidence of prostate cancer."^[24]

The belief that dietary fiber prevents these cancers was based on epidemiological evidence showing a very low incidence in the developing world. Dr. Denis Burkitt was the main proponent of this theory, and his 1979 best-selling book, "Don't Forget Fibre in Your Diet," was translated into nine languages. Less well-known is his theory, mentioned in the book, that the squatting defecation posture used in the developing world where Ottoman toilets are more widespread than the Western world is also a preventative factor, especially for colon diseases.

Methionine metabolism

The methionine metabolism pathway. DHF, dihydrofolate; dSAM, decarboxylated S-adenosylmethionine; hCys, homocysteine; ME, methyl group; MetTR-1-P, 5-methylthioribose-1-phosphate; MT, methyltransferase; MTA, methylthioadenosine; MTHF, methylenetetrahydrofolate; SAH, S-adenosyl-L-homocysteine; SAM, S-adenosyl methionine; SUB, substrate.

Although numerous cellular mechanisms are involved in food intake, many investigations over the past decades have pointed out defects in the methionine metabolic pathway as cause of carcinogenesis.^[25][26] For instance, deficiencies of the main dietary sources of methyl donors, methionine and choline, lead to the formation of liver cancer in rodents.^[27][28] Methionine is an essential amino acid that must be provided by dietary intake of proteins or methyl donors (choline and betaine found in beef, eggs and some vegetables). Assimilated methionine is transformed in S-adenosyl methionine (SAM) which is a key metabolite for polyamine synthesis, e.g. spermidine, and cysteine formation (see the figure on the right). Methionine breakdown products are also recycled back into methionine by homocysteine remethylation and methylthioadenosine (MTA) conversion (see the figure on the right). Vitamins B₆, B₁₂, folic acid and choline are essential cofactors for these reactions. SAM is the substrate for methylation reactions catalyzed by DNA, RNA and protein methyltransferases.

Growth factor (GF) and steroid/retinoid activation of PRMT4.

The products of these reactions are methylated DNA, RNA or proteins and S-adenosylhomocysteine (SAH). SAH has a negative feedback on its own production as an inhibitor of methyltransferase enzymes. Therefore SAM:SAH ratio directly regulates cellular methylation, whereas levels of vitamins B₆, B₁₂, folic acid and choline regulates indirectly the methylation state via the methionine metabolism cycle.^[29][30] A near ubiquitous feature of cancer is a maladaption of the methionine metabolic pathway in response to genetic or environmental conditions resulting in depletion of SAM and/or SAM-dependent methylation. Whether it is deficiency in enzymes such as methylthioadenosine phosphorylase, methionine-dependency of cancer cells, high levels of polyamine synthesis in cancer, or induction of cancer through a diet deprived of extrinsic methyl donors or enhanced in methylation inhibitors, tumor formation is strongly correlated with a decrease in levels of SAM in mice, rats and humans.^[31][32] Many indirect and thinly circumstantial theories have been put forth related to methylation status of DNA or attacks upon the capacity for DNA mutation and repair. The discovery that methyltransferases whose activity would be directly influenced by SAM levels also act as tumor suppressors potentially provides a more direct bridge. This has important ramifications for chemoprevention strategies as well as chemotherapy.^{[33][34][35][36]}

Arginine methyltransferase

Protein arginine N-methyltransferase-4 (PRMT4) methylation of arginine residues within proteins plays a critical key role in transcriptional regulation (see the PRMT4 pathway on the left). PRMT4 binds to the classes of transcriptional activators known as p160 and CBP/p300.^[37] The modified forms of these proteins are involved in stimulation of gene expression via steroid hormone receptors. Significantly, PRMT4 methylates core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. PRMT4 recruitment chromatin by binding to coactivators increases histone methylation and enhances the accessibility of promoter regions for transcription. Methylation of the transcriptional coactivator CBP by PRMT4 inhibits binding to CREB and thereby partitions the limited cellular pool of CBP for steroid hormone receptor interaction.

See also

• Alcohol and cancer
• Alcohol and breast cancer
• DNA methyltransferase
• Food guide pyramid
• List of oncology-related terms
• Red meat
• Nutritional gatekeeper

References

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External links

• Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
• Diet, healthy eating and cancer