Diet & Cancer

Dietary factors are recognized as having a significant effect on the risk of cancers, with different dietary elements both increasing and reducing risk. Diet and obesity may be related to up to 30-35% of cancer deaths,[1] while physical inactivity appears to be related to 7% risk of cancer occurrence.[2] One review in 2011 suggested that total caloric intake influences cancer incidence and possibly progression.[3]

While many dietary recommendations have been proposed to reduce the risk of cancer, few have significant supporting scientific evidence.[3] Obesity and drinking alcohol have been correlated with the incidence and progression of some cancers.[3] Lowering the drinking of beverages sweetened with sugar is recommended as a measure to address obesity.[4] A diet low in fruits and vegetables and high in red meat has been implicated but not confirmed,[5] and the effect may be small for well-nourished people who maintain a healthy weight.[3]

Some specific foods are linked to specific cancers. Studies have linked eating red or processed meat to an increased risk of breast cancer, colon cancer,[4] prostate cancer,[6] and pancreatic cancer, which may be partially explained by the presence of carcinogens in foods cooked at high temperatures.[7][8] Aflatoxin B1, a frequent food contaminate, causes liver cancer,[9] but drinking coffee is associated with a reduced risk.[10] Betel nut chewing causes oral cancer.[9] Pickled vegetables are directly linked to increased risks of several cancers. The differences in dietary practices may partly explain differences in cancer incidence in different countries. For example, stomach cancer is more common in Japan due to its high-salt diet[9][11] and colon cancer is more common in the United States. Immigrant communities tend to develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.[12]

Dietary recommendations for cancer prevention typically include weight management and eating “mainly vegetables, fruit, whole grains and fish, and a reduced intake of red meat, animal fat, and refined sugar.”[3]

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, and some of them have been found to be harmful.[13]

Nutritional epidemiologists use multivariate statistics, such as principal components analysis and factor analysis, to measure how patterns of dietary behavior influence the risk of developing cancer.[14] (The most well-studied dietary pattern is the mediterranean diet.) Based on their dietary pattern score, epidemiologists categorize people into quantiles. To estimate the influence of dietary behavior on risk of cancer, they measure the association between quantiles and the distribution of cancer prevalence (in case-control studies) and cancer incidence (in longitudinal studies). They usually include other variables in their statistical model to account for the other differences between people with and without cancer (confounders). For breast cancer, there is a replicated trend for women with a more “prudent or healthy” diet, i.e. higher in fruitsand vegetables, to have a lower risk of cancer.[15] A “drinker dietary pattern” is also associated with higher breast cancer risk, while the association is inconsistent between a more westernized diet and elevated risk of breast cancer. Pickled foods are linked with cancer.

Alcohol is associated with an increased risk of a number of cancers.[16] 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to drinking of alcohol.[17] Breast cancer in women is linked with alcohol intake.[3][18] Alcohol also increases the risk of cancers of the mouth, esophagus, pharynx and larynx,[19]colorectal cancer,[20][21] liver cancer,[22] stomach[23] and ovaries.[24] 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).”[25]

On October 26, 2015, the International Agency for Research on Cancer of the World Health Organization reported that eating processed meat (e.g., bacon, ham, hot dogs, sausages) or red meat was linked to some cancers.[26][27][28]

The evidence on the effect of dietary fiber on the risk of colon cancer is mixed with some types of evidence showing a benefit and others not.[4] While eating fruit and vegetables has a benefit, it has less benefit on reducing cancer than once thought.[4]

A 2014 study found fruit but not vegetables protected against upper gastrointestinal tract cancer.[29] While fruit, vegetable and fiber protected against colorectal cancer and fiber protected against liver cancer.[29]

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.”[30] While some studies have suggested flavonoids may have a role in cancer prevention, others have been inconclusive or suggested they may be harmful.[31][32]

According to Cancer Research UK, “there is currently no evidence that any type of mushroom or mushroom extract can prevent or cure cancer”, although research into some species continues.[33]

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.[34]

Laboratory experiments have found that turmeric might have an anti-cancer effect.[35] 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.[36]

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.[37][38]A review of all published studies by the US Food and Drug Administration in 2011 concluded it is very unlikely that green tea prevents any kind of cancer in humans.[38]

Resveratrol has shown anti-cancer activity in laboratory experiments, but as of 2009, there is no evidence of an effect on cancer in humans.[39][40]

Vitamin D supplements have been widely marketed on the internet and elsewhere for their claimed anti-cancer properties.[41] There is however insufficient evidence to recommend that vitamin D be prescribed for people with cancer, although there is some evidence that hypovitaminosis D may be associated with a worse outcome for some cancers.[42] A 2014 systematic review by the Cochrane Collaboration found, “no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women.”[43]

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.[44][45] For instance, deficiencies of the main dietary sources of methyl donors, methionine and choline, lead to the formation of liver cancer in rodents.[46][47] 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 methylationreactions 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 methylationstate via the methionine metabolism cycle.[48][49] 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 cancercells, high levels of polyamine synthesis in cancer, or induction of cancer through a diet deprived of extrinsic methyldonors or enhanced in methylation inhibitors, tumor formation is strongly correlated with a decrease in levels of SAM in mice, rats and humans.[50][51]

According to a 2012 review, the effect of methionine restriction on cancer has yet to be studied directly in humans and “there is still insufficient knowledge to give reliable nutritional advice”.[52]

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).[35]

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