Diet and cancer
||This article needs more medical references for verification or relies too heavily on primary sources. (September 2013)|
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, prostate 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 consist of "mainly vegetables, fruit, whole grain and fish and a reduced intake of red meat, animal fat and refined sugar."
- 1 Types of diet
- 2 Dietary components
- 3 Mechanisms of action
- 4 See also
- 5 References
- 6 External links
Types of diet
A number of diets and diet-based regimes are claimed to be useful against cancer. Popular types of "anti-cancer" diet include the Breuss diet, Gerson therapy, the Budwig protocol and the macrobiotic diet. None of these diets has been found to be effective, however some of them have been found to be harmful.
A ketogenic diet generally has not been found to prevent or cure cancer. However, studies in both animals and humans have demonstrated that a ketogenic diet limits tumors' glucose uptake, retarding tumor growth. On such a high-fat, low-carbohydrate diet, healthy cells can convert fatty acids to glucose for energy. However, cancerous cells cannot respire, so without a significant source of glucose from carbohydrates, their growth is retarded. In one study, mice were injected with tumors and then fed different diets. After 51 days, those who ate a ketogenic, no-carbohydrate diet had tumors that were 33% smaller than those who ate a traditional Western diet of equal fat and carbohydrate content.
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.
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)."
Nutrient Bioactives and Cancer
According to the American Cancer Society, although laboratory research has shown the possibility of some connection between soybeans and cancer, as yet there is no conclusive evidence about the anti-cancer effect of soy on human beings.
Laboratory experiments have found that turmeric might have an anti-cancer effect. Although trials are ongoing, large doses would need to be taken for any effect. It is not known what, in any, positive effect turmeric has for human beings with cancer.
Although green tea has been promoted for its anti-cancer effect, research into it has produced mixed results; it is not known if it helps people prevent or treat cancer.
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.
Some studies suggest that high levels of vitamin D in humans may be associated with a reduced cancer risk; however other studies suggest the risk may be greater. The American Cancer Society say more research into this topic is needed.
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." While some studies have suggested flavonoids may have a role in cancer prevention, others have been inconclusive or suggested they may be harmful.
Mechanisms of action
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.
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.
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).
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- Diet, healthy eating and cancer
- European Prospective Investigation into Cancer and Nutrition (EPIC)
- Food, Nutrition, Physical Activity and the Prevention of Cancer: a Global Perspective