Diet and 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]

This advertisement suggests a healthy diet helps to prevent cancer.

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]

Some specific foods are linked to specific cancers. There is strong evidence that processed meat and red meat intake increases risk of colorectal cancer.[5][6][7] Aflatoxin B1, a frequent food contaminant, increases risk of liver cancer,[8] while drinking coffee is associated with a reduced risk.[9] Betel nut chewing causes oral cancer.[8] Stomach cancer is more common in Japan due to its high-salt diet.[8][10] Immigrant communities tend to develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.[11]

Dietary recommendations for cancer prevention typically include weight management and eating a healthy diet, consisting mainly of "vegetables, fruit, whole grains and fish, and a reduced intake of red meat, animal fat, and refined sugar."[3] A healthy dietary pattern may lower cancer risk by 10-20%.[12]

Types of diet

Restrictive diets

A number of diets and diet-based regimes are claimed to be useful against cancer. Popular types of "anti-cancer" diets 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]

Dietary patterns

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 fruits and 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.

Western pattern diet
This section is an excerpt from Western pattern diet § Cancer.[edit]

The Western pattern diet has been generally linked to increased risk for colorectal cancer.[16] Meta-analyses have found that diet patterns consistent with those of the Western pattern diet are positively correlated with risk for prostate cancer.[17][18] Greater adherence to a Western pattern diet was also found to increase the overall risk of mortality due to cancer.[19]

No significant relation has been established between the Western pattern diet and breast cancer.[20][21]

Mediterranean diet
This section is an excerpt from Mediterranean diet § Cancer.[edit]
A meta-analysis in 2008 found that strictly following the Mediterranean diet was correlated with a decreased risk of dying from cancer by 6%.[22] Another 2014 review found that adherence to the Mediterranean diet was associated with a decreased risk of death from cancer.[23] A 2017 review found a decreased rate of cancer, though evidence was weak.[24] An updated review in 2021 found that the Mediterranean diet is associated with a 13% lower risk of cancer mortality in the general population.[25]

Dietary components

Alcohol
Main articles: Alcohol and cancer and Alcohol and breast cancer

Alcohol is associated with an increased risk of a number of cancers.[26] It has been reported that 3.6% of all cancer cases and 3.5% of cancer deaths worldwide are attributable to drinking of alcohol.[27] Breast cancer in women is linked with alcohol intake.[3][28] Alcohol also increases the risk of cancers of the mouth, esophagus, pharynx and larynx,[29] colorectal cancer,[30][31] liver cancer,[32] stomach[33] and ovaries.[34] 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)."[35]

Eggs
This section is an excerpt from Eggs as food § Cancer.[edit]

A 2015 meta-analysis found an association between higher egg consumption (5 a week) with increased risk of breast cancer compared to no egg consumption.[36] Another meta-analysis found that egg consumption may increase ovarian cancer risk.[37]

A 2019 meta-analysis found an association between high egg consumption and risk of upper aero-digestive tract cancers in hospital-based case-control studies.[38]

A 2021 review did not find a significant association between egg consumption and breast cancer.[39] A 2021 umbrella review found that egg consumption significantly increases the risk of ovarian cancer.[40]

Processed and red meat

There is strong evidence that processed meat and red meat intake increases risk of colorectal cancer.[41][42][43] The American Cancer Society in their "Diet and Physical Activity Guideline", stated "evidence that red and processed meats increase cancer risk has existed for decades, and many health organizations recommend limiting or avoiding these foods."[44]

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 and classed them as Group 1 (carcinogenic to humans) and Group 2a (probably carcinogenic to humans) carcinogens respectively.[45] There is some evidence that suggests that heme and nitrite are involved in the processes linking red and processed meat intake with colorectal cancer.[45] Heme is present in particular in red meat and nitrite is used as curing salt in many processed meats.

Salted fish
This section is an excerpt from Salted fish § Health effects.[edit]
The American Institute for Cancer Research (AICR) and World Cancer Research Fund International (WCRF) have stated that there is strong evidence obtained mostly from Asia that consuming salted fish increases risk of stomach cancer and consuming Cantonese-style salted fish increases risk of nasopharyngeal cancer.[46][47] The International Agency for Research on Cancer classify salted fish (Chinese-style) as a Group 1 carcinogen.[48][49]

Fiber, fruits and vegetables

There is strong evidence that consumption of dietary fiber reduces risk of colorectal cancer.[50][51][52] Two 2020 meta-analyses found that a high fiber intake was associated with a lower risk of both premenopausal and postmenopausal breast cancers[53] and a higher survival rate in patients with breast cancer.[54]

A 2021 review found that there is moderate-quality evidence 200g of fruit intake per day is associated with a lower risk of breast cancer.[55] Another review found that high total fruit and vegetable consumption are associated with reduced risk of breast cancer.[56]

Pickled vegetables
This section is an excerpt from Pickling § Possible health hazards of pickled vegetables.[edit]

The World Health Organization has listed pickled vegetables as a possible carcinogen, and the British Journal of Cancer released an online 2009 meta-analysis of research on pickles as increasing the risks of esophageal cancer. The report, citing limited data in a statistical meta analysis, indicates a potential two-fold increased risk of oesophageal cancer associated with Asian pickled vegetable consumption. Results from the research are described as having "high heterogeneity" and the study said that further well-designed prospective studies were warranted.[57] However, their results stated "The majority of subgroup analyses showed a statistically significant association between consuming pickled vegetables and Oesophageal Squamous Cell Carcinoma".[57]

The 2009 meta-analysis reported heavy infestation of pickled vegetables with fungi. Some common fungi can facilitate the formation of N-nitroso compounds, which are strong oesophageal carcinogens in several animal models.[58] Roussin red methyl ester,[59] a non-alkylating nitroso compound with tumour-promoting effect in vitro, was identified in pickles from Linzhou, Henan (formerly Linxian) in much higher concentrations than in samples from low-incidence areas. Fumonisin mycotoxins have been shown to cause liver and kidney tumours in rodents.[57]

A 2017 study in Chinese Journal of Cancer[60] has linked salted vegetables (pickled mustard green common among Chinese cuisine) to a fourfold increase in nasopharynx cancer. The researchers believe possible mechanisms include production of nitrosamines (a type of N-nitroso compound) by fermentation and activation of Epstein–Barr virus by fermentation products.[61][62]

Historically, pickling caused health concerns for reasons associated with copper salts, as explained in the mid-19th century The English and Australian Cookery Book: "The evidence of the Lancet commissioner (Dr. Hassall) and Mr. Blackwell (of the eminent firm of Crosse and Blackwell) went to prove that the pickles sold in the shops are nearly always artificially coloured, and are thus rendered highly unwholesome, if not actually poisonous."

Flavonoids

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."[63] While some studies have suggested flavonoids may have a role in cancer prevention, others have been inconclusive or suggested they may be harmful.[64][65]

Mushrooms

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.[66]

Dairy products
This section is an excerpt from Dairy product § Cancer.[edit]

The American Institute for Cancer Research (AICR), World Cancer Research Fund International (WCRF), Cancer Council Australia (CCA) and Cancer Research UK have stated that there is strong evidence that consumption of dairy products decreases risk of colorectal cancer.[67][68][69][70] The AICR, WCRF, CCA and Prostate Cancer UK have stated that there is limited but suggestive evidence that dairy products increase risk of prostate cancer.[67][68][69][71][72] The American Cancer Society (ACS) have stated that because dairy products "may lower the risk of some cancers and possibly increase the risk of others, the ACS does not make specific recommendations on dairy food consumption for cancer prevention."[73]

It has been suggested that consumption of insulin-like growth factor 1 (IGF-1) in dairy products could increase cancer risk, particularly prostate cancer.[74][75] However, a 2018 review by the Committee on Carcinogenicity of Chemicals in Food, Consumer Products and the Environment (COC) concluded that there is "insufficient evidence to draw any firm conclusions as to whether exposure to dietary IGF-1 is associated with an increased incidence of cancer in consumers".[75] The COC also stated it is unlikely that there would be absorption of intact IGF-1 from food by most consumers.[76]

A 2019 review concluded that higher-quality research was needed to characterise valid associations between dairy consumption and risk of and/or cancer-related mortality.[77] A 2021 umbrella review found strong evidence that consumption of dairy products decreases risk of colorectal cancer.[78] Fermented dairy is associated with significantly decreased bladder cancer and colorectal cancer risk.[79]

A 2023 review found no association between consumption of dairy products and breast cancer.[80]

Whole grains

There is strong evidence that consumption of whole grains decreases risk of colorectal cancer.[51][81][82][83]

Saturated fat
This section is an excerpt from Saturated fat § Cancer.[edit]

Several reviews of case–control studies have found that saturated fat intake is associated with breast cancer risk and mortality.[84][85][86]

Observational studies have shown that a diet high in saturated fat increases the risk of prostate cancer.[87]

Other
  • According to the American Cancer Society, there is no conclusive evidence for an anticancer effect of consuming soy products.[88]
  • Green tea consumption has no effect on cancer risk.[89][90][91]
  • A 2016 meta-analysis showed that women and men who drank coffee had a lower risk of liver cancer.[9] An umbrella review of meta-analyses found that coffee was associated with a lower risk of liver and endometrial cancer.[92]
  • A 2014 systematic review found, "no firm evidence that vitamin D supplementation affects cancer occurrence in predominantly elderly community-dwelling women."[93]

Mechanisms of action

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.[94][95] For instance, deficiencies of the main dietary sources of methyl donors, methionine and choline, lead to the formation of liver cancer in rodents.[96][97] 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.[98][99] 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.[100][101]

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".[102]

AMPK

AMPK is thought to be a major element or mechanism in cancer-related effects of diet. It modulates the activity of cellular survival signaling such as mTOR and Akt, leading to cell growth inhibition which is relevant to cancer growth. Targeting AMPK has become a novel strategy for cancer prevention and treatment.[103][104][105] Potential complementary or preventive options under investigation include periods of caloric restriction and AMPK agonists (typically mTOR inhibitors).[106][107][108][109][110][111] However, AMPK can also promote cancer in some settings.[103][108]

See also

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