Cancer and Diet
Almost all cancers (80–90%) are caused by environmental factors, and of these, 30–40% of cancers are directly linked to the diet. While many dietary recommendations have been proposed to reduce the risk of cancer, few have significant supporting scientific evidence. The primary dietary factors that increase risk are obesity and alcohol consumption; with a diet low in fruits and vegetables and high in red meat being implicated but not confirmed. Consumption of coffee is associated with a reduced risk of liver cancer. Studies have linked consumption of red or processed meat to an increased risk of breast cancer, colon cancer, and pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in foods cooked at high temperatures. Thus dietary recommendations for cancer prevention typically include: “mainly vegetables, fruit, whole grain and fish and a reduced intake of red meat, animal fat and refined sugar.”
Fiber, Fruits and Vegetables
Recent studies have cast doubt on the claim that dietary fiber reduces the risk of colon cancer. 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.” In April 2010, the results of a major study involving 500,000 people in Europe suggested that consumption of fruit and vegetables had little impact on reducing cancer.
Currently there is not enough evidence for using mushrooms or mushroom extracts in the treatment of cancer, and rigorous clinical trials are needed to demonstrate any potential effectiveness or toxicity of mushrooms or mushroom extract.
Main articles: Alcohol and cancer and Alcohol and breast cancer
Alcohol is associated with an increased risk of a number of cancers. 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to consumption of alcohol. Breast cancer in women is linked with alcohol intake. Alcohol also increases the risk of cancers of the mouth, esophagus, pharynx and larynx, colorectal cancer, liver cancer, stomach and ovaries. The International Agency for Research on Cancer (Centre International de Recherche sur le Cancer) of the World Health Organization has classified alcohol as a Group 1 carcinogen. Its evaluation states, “There is sufficient evidence for the carcinogenicity of alcoholic beverages in humans. …Alcoholic beverages are carcinogenic to humans (Group 1).”
Flavonoids (specifically flavonoids such as the catechins) are “the most common group of polyphenolic compounds in the human diet and are found ubiquitously in plants.” The widespread distribution of flavonoids, their variety and their relatively low toxicity compared to other active phytocompounds (for instance alkaloids) mean that many animals, including humans, ingest significant quantities in their diet. Foods such as green and black tea, chocolate, wine, and grapes provide the most the significant source of flavonoids in the human diet.
Recently, flavonoids (specifically catechins) have emerged as potential anticancer agents. Although much of the research is still in a preliminary stage, it is clear that flavonoids might induce mechanisms that affect cancer cells and inhibit tumor invasion. UCLA cancer researchers have proposed that smokers who ate foods containing certain flavonoids, such as the flavan-3-ols (catechins) found in strawberries and green and black teas, kaempferol from brussel sprouts and apples, and quercetin from beans, onions and apples, may have reduced risk of developing lung cancer.
Other examples of 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, thus potentially lowering the risk of cells turning cancerous.
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. For instance, deficiencies of the main dietary sources of methyl donors, methionine and choline, lead to the formation of liver cancer in rodents. 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. 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. 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.
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. 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.
Chemotherapy damages tissue causing it to secrete novel factors that sustain the growth of tumor cells which leads to treatment resistance. A study has been done to show the effects of a sub-type of chemotherapy regimes that cause DNA damage and trigger an inflammatory response on fibroblast cells found in prostate tumors. Multiple oncogenic signaling pathways have been involved in the processes of cancer cell invasion and metastasis. Among these signaling pathways, Wnt and Hedgehog signaling pathways are involved in the embryonic development, in the biology of cancer stem cells (CSCs) and in the acquisition of epithelial to mesenchymal transition (EMT). Evidence suggests the beneficial role of chemopreventive agents known as nutraceutical in cancer. Among many such agents – soy isoflavones, curcumin, green tea polyphenols, 3,3′-diindolylmethane, resveratrol, lycopene, vitamin D, etc. – have been found to prevent, reverse, or delay the carcinogenic process. These agents have also shown to prevent or delay the development of cancer, which is possibly due to their ability to attack CSCs or EMT-type cells by altering the Wnt and Hedgehog signaling pathways.
Several studies have shown that soy could have protective effects against prostate and other cancers. A study of 12,395 California Seventh-Day Adventist men who often drank soy milk showed that frequent consumption of soy milk was associated with 70% reduction of the risk of prostate cancer. Other Studies have also revealed that isoflavones exert anti-oxidant effects on human cells. Investigators have found that curcumin could inhibit several important signaling pathways Wnt signaling and Hedgehog signaling. Through the inhibition of Wnt signaling, consuming curcumin has been shown to decrease the size of tumors in breast cancer cells, colon cancer, medulloblastoma, and prostate cancer. Studies show lower incidences of prostate cancer among Asian men with a high diet of green tea, suggesting that green tea might be preventive against cancers. By regulation of cell proliferation and apoptosis, resveratrol has been shown to restrain many types of cancers. Studies also showed that lycopene suppressed cell growth in breast, prostate, and endometrial cancer cells. Experiments also suggest that an increased consumption of vitamin D is associated with reducing the risks of cancers and can prevent some cancers as well.
Alcohol and cancer
Alcohol and breast cancer
Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective
Diet, healthy eating and cancer
Amino acids Bodybuilding supplement Energy drink Energy bar Fatty acids Herbal Supplements Minerals Prebiotics Probiotics (Lactobacillus Bifidobacterium) Protein bar Vitamins
“minerals” (chemical elements)
Retinol (Vitamin A) B vitamins: Thiamine (B1) Riboflavin (B2) Niacin (B3) Pantothenic acid (B5) Pyridoxine (B6) Biotin (B7) Folic acid (B9) Cyanocobalamin (B12) Ascorbic acid (Vitamin C) Ergocalciferol and Cholecalciferol (Vitamin D) Tocopherol (Vitamin E) Naphthoquinone (Vitamin K) Calcium Choline Chromium Cobalt Copper Fluorine Iodine Iron Magnesium Manganese Molybdenum Phosphorus Potassium Selenium Sodium Sulfur Zinc
Other common ingredients
AAKG Carnitine Chondroitin sulfate Cod liver oil Copper gluconate Creatine/Creatine supplements Dietary fiber Echinacea Elemental calcium Ephedra Fish oil Folic acid Ginseng Glucosamine Glutamine Grape seed extract Guarana Iron supplements Japanese Honeysuckle Krill oil Lingzhi Linseed oil Lipoic acid Milk thistle Melatonin Red yeast rice Royal jelly Saw palmetto Spirulina St John’s wort Taurine Wheatgrass Wolfberry Yohimbine Zinc gluconate
Codex Alimentarius Enzyte Hadacol Nutraceutical Multivitamin Nutrition Tisane
α-Carotene · β-Carotene · Retinol# · Tretinoin
D2 (Ergosterol, Ergocalciferol#) · D3 (7-Dehydrocholesterol, Previtamin D3, Cholecalciferol, 25-hydroxycholecalciferol, Calcitriol (1,25-dihydroxycholecalciferol), Calcitroic acid) · D4 (Dihydroergocalciferol) · D5 · D analogues (Alfacalcidol, Dihydrotachysterol, Calcipotriol, Tacalcitol, Paricalcitol)
Tocopherol (Alpha, Beta, Gamma, Delta) · Tocotrienol (Alpha, Beta, Gamma, Delta) · Tocofersolan
Naphthoquinone · Phylloquinone (K1) · Menaquinones (K2) · Menadione (K3) · Menadiol (K4)
B1 (Thiamine#) · B2 (Riboflavin#) · B3 (Niacin, Nicotinamide#) · B5 (Pantothenic acid, Dexpanthenol, Pantethine) · B6 (Pyridoxine#, Pyridoxal phosphate, Pyridoxamine) · B7 (Biotin) · B9 (Folic acid, Dihydrofolic acid, Folinic acid, L-methylfolate) · B12 (Cyanocobalamin, Hydroxocobalamin, Methylcobalamin, Cobamamide) · Choline
Ascorbic acid# · Dehydroascorbic acid
# WHO-EM ‡ Withdrawn from market Clinical trials:
† Phase III § Never to phase III
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Nutrition disorders (E40–E68, 260–269)
Kwashiorkor · Marasmus · Catabolysis
B1: Beriberi/Wernicke’s encephalopathy (Thiamine deficiency) · B2: Ariboflavinosis · B3: Pellagra (Niacin deficiency) · B6: Pyridoxine deficiency · B7: Biotin deficiency · B9: Folate deficiency · B12: Vitamin B12 deficiency
A: Vitamin A deficiency/Bitot’s spots · C: Scurvy · D: Hypovitaminosis D/Rickets/Osteomalacia · E: Vitamin E deficiency · K: Vitamin K deficiency
Sodium · Potassium · Magnesium · Calcium · Iron · Zinc · Manganese · Copper · Iodine · Chromium · Molybdenum · Selenium (Keshan disease)
Overweight · Obesity
Childhood obesity · Obesity hypoventilation syndrome · Abdominal obesity
Hypervitaminosis A · Hypervitaminosis D · Hypervitaminosis E
see inborn errors of metal metabolism, toxicity
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Pathology: Tumor, Neoplasm, Cancer, and Oncology (C00–D48, 140–239)
Hyperplasia Cyst Pseudocyst Hamartoma
Dysplasia Carcinoma in situ Cancer Metastasis
Head/Neck (Oral, Nasopharyngeal) Digestive system Respiratory system Bone Skin Blood Urogenital Nervous system Endocrine system
Carcinoma Sarcoma Blastoma Papilloma Adenoma
Precancerous condition Paraneoplastic syndrome
TNM Ann Arbor Prostate cancer staging Gleason Grading System Dukes classification
Cancer cell Carcinogen Tumor suppressor genes/oncogenes Clonally transmissible cancer Oncovirus Cancer bacteria
Research List of oncology-related terms History Cancer pain
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