Micronutrient Information Center

Summary

The large intestine includes the cecum, the colon, the rectum, and the anal canal. The colon is described according to four anatomic regions, from the cecum to the rectum: ascending colon, transverse colon, descending colon, and sigmoid colon. Its physiological function is to process and absorb undigested nutrients, absorb electrolytes and water, and excrete waste products via the rectum.

The intestinal epithelium is entirely renewed every three to five days. The single layer of epithelial cells is derived from immature cells that multiply in the small pits (called colonic crypts) located throughout the intestinal epithelium. Unlike the epithelium of the small intestine, the colonic epithelium is flat and does not have villi.

Colorectal cancer is the most common gastrointestinal cancer, accounting for over 1.8 million new cases per year worldwide. It is also the second leading cause of death by cancer (behind lung cancer) in the US. The development of colorectal cancer is associated with alterations of different molecular processes driving the transformation of normal cells into cancer cells. These alterations may be almost entirely caused by inherited genetic mutations as in individuals with familial adenomatous polyposis or by modifiable lifestyle factors and chronic inflammation in cases of non-hereditary (sporadic) colorectal cancer.

Disease Overview

Incidence

In 2018, over 1.8 million people worldwide received a diagnosis of colorectal cancer (1). Colorectal cancer is the third most commonly diagnosed cancer in men, after lung and prostate cancers, and the second in women, after breast cancer.

• The disease affects more men than women: on average, 23.6 new cases per 100,000 among men versus 16.3 new cases per 100,000 among women (1).
• The highest incidence in men (≥35.7 new cases per 100,000) and women (≥24.5 new cases per 100,000) is reported in populations of high-income countries: Europe, Australia, New Zealand, South Korea, Japan, and North America (1).
• The incidence is rising in low- and middle-income countries as they undergo rapid societal and economic development. The incidence keeps increasing in high-income countries like Canada, UK, Denmark, and Singapore, but is decreasing in the US, Japan, and France (2).
• In the US, colorectal cancer is most common in Blacks (42.2 new cases per 100,000) and least common is Asians/Pacific islanders (29 new cases per 100,000) (3).

Adenoma-carcinoma sequence

The adenoma-carcinoma sequence describes the development of colorectal cancer from normal epithelium to carcinoma with the concomitant accumulation of epigenetic and genetic anomalies (4).

Colorectal adenomas (also called adenomatous polyps) are considered to be precursor lesions for most cases of colorectal cancer within the adenoma-carcinoma sequence. For a subtype of colorectal cancer called serrated adenocarcinoma, the early lesions are sessile serrated polyps rather than adenomatous polyps.

Classification

Most colorectal cancers are adenocarcinomas. They can be classified according to molecular subtype; this helps stratify patients into good and poor prognosis groups and personalize treatment options (5, 6).

Etiology

There is not one single cause of colorectal cancer. Instead, a number of factors, either modifiable or non-modifiable, can influence the risk of developing colorectal cancer.

Genetic factors

Hereditary colorectal cancer: About 5% of people diagnosed with colorectal cancer have inherited genetic predispositions. These genetic predispositions give rise to a number of colorectal cancer syndromes. The two most common syndromes are hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) and familial adenomatous polyposis (FAP).

HNPCC is associated with mutations in genes involved in DNA repair, while FAP is associated with alterations in the specific genes, APC and MUTYH.

Familial colorectal cancer: About 15%-30% of colorectal cancer cases occur in people with a family history of colorectal adenoma/cancer.

Sporadic colorectal cancer: The large majority of colorectal cancer cases are not related to family history or inherited factors. Sporadic colorectal cancers are primarily linked to diet, lifestyle, and environmental factors, which can lead to genetic mutations and epigenetic anomalies. Several genetic pathways have been involved in the development of sporadic cases of colorectal cancer.

Inflammatory bowel disease

People experiencing ulcerative colitis or Crohn’s disease have a higher risk of colorectal cancer.

Unhealthy diets and lifestyle factors

Diet is closely associated with colorectal cancer. High intakes of fruit and vegetables, dairy products, fish, and fiber are thought to protect against colorectal cancer, while consumption of high amounts of red and processed meats is likely to increase the risk of colorectal cancer. Cigarette smoking, alcohol consumption, and physical inactivity also contribute to increasing the risk of colorectal cancer.

Other risk factors

Increasing age, male gender, and obesity are associated with a higher risk of developing colorectal cancer.

References:

Aran et al. (2016) (5)
Kuipers et al. (2015) (7)
Connell et al. (2017) (8)

Prevention and Screening

The American Cancer Society has developed recommendations, highlighting the importance of weight control, physical activity, and a healthy diet, for the primary prevention of cancer (9). Most colorectal cancer cases are connected to diet and lifestyle. Achieving and maintaining a healthy weight throughout life, being physically active, and consuming a healthy diet with an emphasis on fruit and vegetables, while limiting alcohol drinks and avoiding tobacco smoking, should lower one’s risk of developing sporadic colorectal cancer.

Screening is meant to detect early lesions in people who have no symptoms of the disease. It takes between 10 to 15 years for abnormal colorectal cells to grow into polyps. Regular screening allows the detection and removal of polyps. Additionally, detecting colorectal cancers when they are small makes them easier to treat and cure. Screening tests include stool-based tests and colonoscopy. Age-specific recommendations for cancer screening are provided by the American Cancer Society.

Nutrition Research

Dietary Fat

What it does

General

• Fat in the diet is a major source of energy for the body, providing 9 calories per gram (g).
• Types (saturated, monounsaturated, polyunsaturated [including essential], and trans fatty acids) and amounts of fat in one’s diet have been linked to either harms or benefits to health.
• Dietary guidelines recommend avoiding trans fat, limiting saturated fat (<10% of total energy intake), and replacing saturated fat by mono/polyunsaturated fat (10, 11).

Cancer-specific

• In animal experiments, omega-3 fatty acids (a type of polyunsaturated fatty acids) and their derivatives reduced the risk of cancer by triggering mechanisms against inflammation, oxidative stress, and abnormal cell proliferation (12, 13).

What we know

• Consumption of all or specific types of fatty acids from food sources is not associated with a lower or higher risk of colorectal cancer (14).
• Fish oil or omega-3 fatty acid supplements are currently being evaluated for use as an adjunct to chemotherapy in patients with colorectal cancer. These fatty acids may increase the tolerability and/or therapeutic response to anticancer drugs (13).

For references and more information, the 2015-2020 Dietary Guidelines for Americans provide detailed advice on fat consumption. Specific recommendations for essential fatty acid (omega-3 and omega-6) intake can also be found in the Essential Fatty Acids article.

Fiber

What it does

General

• Fiber is a general term for (primarily) carbohydrates that are resistant to digestion by human enzymes.
• Fiber may be obtained from food sources, additives, and dietary supplements.
• As fiber travels through the digestive tract, its physical properties (which vary depending on the type of fiber ingested) impart different health effects.

• Mechanisms by which fiber may exert health benefits on the gastrointestinal and cardiovascular systems include glycemic control, cholesterol and blood pressure lowering, and regulation of stool consistency and elimination.

Cancer-specific

• Fiber consumption may protect the digestive tract by reducing exposure of the mucosa to carcinogens. Additionally, the fermentation of certain fibers in the large intestine releases short-chain fatty acids that have anticancer activities.
• There is evidence showing that higher fiber intakes are associated with reduced risks of cancers of the digestive tract (in particular esophageal, gastric, colorectal, and pancreatic cancers), as well as breast and, possibly, ovarian and prostate cancers.

What we know

• High intakes of fiber-rich foods are associated with a lower risk of colorectal cancer (15).

For references and more information, see the section on colorectal cancer in the Fiber article.

Calcium

What it does

General

• Calcium is a major structural component of bones and teeth.
• Calcium plays an essential role in cell-signaling pathways and is therefore fundamental to virtually all physiological functions.
• Dairy products contribute to 75% of calcium intakes in the American diet.

Cancer-specific

• A calcium-sensing receptor that helps maintain blood calcium within a tight concentration range is expressed throughout the intestines. This receptor is thought to be involved in the regulation of inflammatory pathways and to act as a tumor suppressor in the large intestine (16).

What we know

• Higher intakes of calcium from food (17, 18) or supplements (18) are associated with a lower risk of colorectal cancer.
• Specifically, a 300 mg/day increase in calcium intake — from diet or from supplements — is associated with an 8% lower risk of colorectal cancer (18).

• Supplementation with calcium (1.2-2 g/day for up to 5 years) reduces the risk of colorectal adenomas in people with a history of colorectal adenoma or cancer (19, 20).

For general information about calcium, see the Calcium article.

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Folate

What it does

General

• Folate is a B-vitamin that is required for DNA synthesis and the formation of new cells. The vitamin is specifically involved in the synthesis of thymine, an essential DNA component.
• The B-vitamins folate, riboflavin, vitamin B₁₂, and vitamin B₆ work together to convert homocysteine to methionine, an amino acid important for methylation reactions and countless other cellular activities.

Cancer-specific

• Folate deficiency may increase genomic instability and chromosome breakage, thereby contributing to cancer development.
• Conversely, it has been argued that folate supplementation could fuel cell multiplication and thus promote cancer development. However, there is no evidence in humans that folate supplementation or consumption of fortified food increases the risk of any cancer type.
• Anti-folate molecules that interfere with DNA synthesis are successfully used in anticancer therapies.

What we know

• Poor folate status (21) and certain genetic variations in the metabolism of folate (22) have been associated with an increased risk of developing colorectal cancer.
• Folic acid supplementation may protect people with low folate status against primary or recurrent colorectal tumors; e.g., people with inflammatory bowel disease who are at risk of folate deficiency may benefit from folic acid supplementation in terms of colorectal cancer prevention (23). Yet, there is no additional benefit to those who are already replete (24, 25).
• Follow-up of a randomized controlled trial suggested than folic acid supplementation (1 mg/day) may increase the risk of sessile serrated adenomas (26).

For more information, see the section on colorectal cancer in the Folate article.

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Iron

What it does

General

• Iron is an essential component of hundreds of essential proteins involved in a wide range of activities, such as oxygen transport and storage, energy metabolism, and DNA synthesis.
• Some of these proteins, including hemoglobin, cytochromes, and antioxidant enzymes, require iron-containing heme to carry out their biological activities. 

Cancer-specific

• Free (unbound) iron can react with hydrogen peroxide to generate hydroxyl radicals. Iron can also contribute to the formation of nitrosamines. Both types of compounds can damage DNA and increase the risk of cancer.

What we know

• High consumption of heme iron, mainly from red meat, has been associated with a higher risk of colorectal cancer (28). 

For references and more information, see the section on cancer in the Iron article.

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Magnesium

What it does

General

• Magnesium is a cofactor for enzymes that catalyze hundreds of essential reactions in the metabolism of carbohydrates, fats, and proteins.
• Magnesium is required for the synthesis of ATP, which is involved in virtually all cellular processes.

Cancer-specific

• Magnesium binds to negatively charged molecules and has a structural role in chromosomes and cell membranes. Magnesium deficiency is thus likely to affect genome stability.
• Magnesium is involved in key cell functions, including proliferation and migration, which are altered in cancer.

What we know

• Higher magnesium intakes in a representative sample of the US population have been linked to lower risk of poor vitamin D status. Adequate vitamin D status is associated with a lower risk of developing colorectal cancer.
• Higher magnesium intakes are associated with a lower risk of developing colorectal cancer (17).

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Riboflavin

What it does

General

• Riboflavin (vitamin B₂) is a water-soluble vitamin that assists several metabolic and antioxidant enzymes and helps convert food into useable energy.
• Riboflavin is needed to convert folate to a form needed to maintain normal concentrations of homocysteine in blood and to support methylation reactions in the body.

Cancer-specific

• Poor riboflavin status can affect folate metabolism, thereby potentially increasing the risk of cancer.

What we know

• The available evidence is mixed regarding the potential association between higher intakes of riboflavin and lower risk of colorectal cancer (29-31).

For more information, see the section on cancer prevention in the Riboflavin article.

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Selenium

What it does

General

• Selenium is an essential trace mineral required for the synthesis of a particular amino acid called selenocysteine.
• Selenocysteine is a structural component of at least 25 proteins, including enzymes involved in the making of thyroid hormones, as well as several antioxidant enzymes.

Cancer-specific

• Deficiency in selenium might compromise antioxidant enzyme activities that protect essential cell constituents against oxidative damage. Oxidative damage to DNA in particular may play a role in the development of cancer.

• Trials have found no benefit of selenium supplements in the prevention of total cancer, specific types of cancer, or mortality related to cancer (32).

What we know

• Some, but not all, observational studies reported a lower risk of colorectal cancer with higher selenium intakes (from diet and supplements) or higher selenium nutritional status (32, 33).
• In general, randomized controlled trials have not found selenium supplementation lowers risk of colorectal cancer occurrence or recurrence (see the article on Selenium).

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Vitamin A

What it does

General

• Vitamin A refers to a number of fat-soluble vitamins (collectively known as retinoids) involved in the growth and differentiation of virtually all cells in the body.
• Vitamin A is essential for normal vision, reproduction, development, and immune function.
• Retinol is a ready-to-use form of vitamin A present in the body and food of animal origin. β-Carotene and other carotenoids in plants can be converted (to some extent) into retinol by the body (see Carotenoids below).

Cancer-specific

• Test tube and animal experiments showed that all-trans retinoic acid — a biologically active form of vitamin A — can stop the multiplication and spread of cancer cells and trigger their death (34).
• Several retinoids are approved for the treatment of cancers, such as neuroblastoma and certain lymphomas (35).

What we know

• Higher intakes of vitamin A from food sources and/or supplements have not been associated with a lower risk of colorectal cancer (29, 36, 37).

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Vitamin B₆

What it does

General

• Vitamin B₆ and its derivative pyridoxal 5’-phosphate (PLP) are essential for over 100 enzymes involved in the production of energy and the synthesis of neurotransmitters, hemoglobin, and DNA.
• Additionally, the B-vitamins folate, vitamin B₁₂, and vitamin B₆ work together in the so-called 'one-carbon metabolic pathway' to maintain normal concentrations of homocysteine in blood.
• Vitamin B₆ is found in a variety of foods, including fish, poultry, nuts, legumes, starchy vegetables, avocados, and bananas.

Cancer-specific

• Deficiency in vitamin B₆ may lead to anomalies in DNA synthesis and methylation, thereby contributing to cancer development.

What we know

• Higher dietary intakes of vitamin B₆ and higher blood PLP concentrations are associated with a lower risk of colorectal cancer (29, 38-40).
• No trial has been designed to examine whether supplementation with vitamin B₆ alone could be protective against any cancer, including colorectal cancer (38).

For more information, see the section on Gastrointestinal cancers in the Vitamin B₆ article.

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Vitamin C

What it does

General

• Vitamin C (ascorbic acid) is a water-soluble vitamin that neutralizes a variety of reactive oxygen species and recycles important cellular antioxidants (including vitamin E).
• Vitamin C is also a cofactor in enzymatic reactions involved in the regulation of gene expression and in the making of collagen, L-carnitine, and several neurotransmitters.

Cancer-specific

• Vitamin C is a cofactor for enzymes that influence the methylation of DNA. DNA methylation plays a crucial role in the stability of the genome and alterations of DNA methylation profile are one feature of cancer development.
• Vitamin C is an antioxidant that might protect the gastrointestinal lining from oxidative damage and contribute to limit the formation of cancer-causing agents like nitrosamines in the stomach (41).

What we know

• Limited evidence suggests a lower risk of colorectal adenoma (37) — but not colorectal cancer (29, 36, 42) — with higher intakes of vitamin C from food and/or supplements.

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Vitamin D

What it does

General

• Vitamin D is made in the skin upon sunlight (UV) exposure and can also be obtained from a few foods or supplements.
• Vitamin D is a fat-soluble vitamin that helps regulate calcium and phosphorus homeostasis, promotes bone health and immune function, and influences cell growth and development.

Cancer-specific

• Test tube and animal experiments showed that vitamin D can stop the multiplication and trigger the death of various types of cancer cells.
• Vitamin D helps strengthen the immune system and limit chronic inflammatory processes that often precede cancer development (43).
• Low vitamin D status has been associated with a higher risk of dying prematurely from cancer.

What we know

• Adequate vitamin D status is associated with a lower risk of developing colorectal cancer (44, 45) and a better survival rate in patients diagnosed with the disease (46-48).

For more information, see the section on colorectal cancer in the Vitamin D article.

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Zinc

What it does

General

• Zinc is an essential trace mineral that is required for the synthesis of hundreds of essential proteins, facilitates oxygen transport and storage, and assists several antioxidant enzymes.

Cancer-specific

• High intake of red meat, rich in heme iron and zinc, is associated with a higher risk of colorectal cancer.
• However, unlike iron, zinc is an antioxidant with potential anticancer activities (49, 50).

What we know

• Dietary zinc deficiency is common, affecting primarily populations in low- and middle-income countries whose diets lack foods of animal origin.
• Higher zinc intakes from food have been associated with a lower risk of developing colorectal cancer (51, 52).

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Carotenoids

What they do

General

• Carotenoids are yellow, orange, and red pigments found in fruit and vegetables. We can distinguish:
  • Those which the body can use to form vitamin A; i.e., α-carotene, β-carotene, and β-cryptoxanthin;
  • Those which cannot be converted to vitamin A; i.e., lutein, zeaxanthin, and lycopene.
• Lutein and zeaxanthin can protect specialized cells in the retina against oxidative damage.

Cancer-specific

• Carotenoids have demonstrated anticancer activities in test tube experiments (53).

• Supplementation with β-carotene has not resulted in a reduction in overall cancer risk (54).

• People at risk for lung cancer, including smokers, are advised not to use β-carotene supplements (54).

What we know

• Observational studies have found no association between high intakes of carotenoids and the risk of colorectal cancer (55, 56).

• Regular intake of β-carotene supplements has not been associated with any harm or benefit regarding the risk of colorectal cancer, even in smokers (54).

For references and more information, read the section in the on Carotenoids article.

Curcumin

What it does

General

• Curcumin is a naturally occurring plant chemical that is abundant in the spice turmeric.
• Experiments performed in test tubes indicated that curcumin can trigger antioxidant and anti-inflammatory defense systems within cells.
• Animal experiments showed a protective effect of curcumin against stress-induced ulcers and other lesions of the gastric mucosa caused by the chronic use of drugs (e.g., NSAIDs) (57).

Cancer-specific

• The results of pilot studies suggest that high doses of oral curcumin might help improve tumor-related markers and provide symptomatic relief in patients with cancer (58).
• The therapeutic efficacy of oral curcumin administration depends on the bioavailability of curcumin, which is very low since curcumin is readily excreted by the body upon absorption. Innovative solutions are being developed to improve curcumin bioavailability (59).

What we know

• Oral administration of curcumin (3 g/day for one year) to patients with familial adenomatous polyposis was found to be safe and well tolerated yet had no effect on the size and number of tumors (60).

For references and more information, see the sections on Cancer prevention and Cancer treatment in the article on curcumin.

Flavonoids

What they do

General

• Flavonoids are plant chemicals that belong to a class of compounds called phenols.
• Six major subclasses of flavonoids are widely found in edible plants: anthocyanidins, flavan-3-ols, flavonols, flavones, flavanones, and isoflavones.
• High intakes of flavonoid-rich foods are associated with a 26% lower risk of premature death (61).

Cancer-specific

• In test tube and animal experiments, flavonoids showed anticancer activities, including abilities to scavenge free radicals, trigger carcinogen excretion, and prevent the multiplication and spread of abnormal cells.

What we know

• There is no consistent evidence to suggest that high intakes of flavonoid-rich food and beverages are associated with a lower risk of developing colorectal cancer (62-69).

For references and more information, see the sections on Cancer prevention and Cancer treatment in the article on flavonoids.

Isothiocyanates

What they do

General

• Isothiocyanates are compounds formed from glucosinolates found in cruciferous vegetables (e.g., Brussels sprouts, kale, broccoli, bok choy).
• Most prominent isothiocyanates include benzyl isothiocyanate, phenethyl isothiocyanate, and sulforaphane.

Cancer-specific

• In animal experiments, isothiocyanates limited the development of chemically induced tumors of several tissues, including the colon.
  • Potential mechanisms of action include the elimination of carcinogens, protection of cells/tissues from oxidative damage, and inhibition of multiplication and spread of cancerous cells.
• Test tube and animal experiments suggest that isothiocyanates could be beneficial as an adjunct therapy with anticancer drugs (70).

What we know

• High intakes of cruciferous vegetables may be associated with a lower risk of developing colorectal cancer, yet the available evidence is mixed (71-73).

For references and more information, see the sections on cancer prevention in the articles on Isothiocyanates and Cruciferous Vegetables.

Phytosterols

What they do

General

• Phytosterols are compounds that are structurally similar to cholesterol; phytosterols are found in unrefined vegetable oils, whole grains, seeds, nuts, and legumes.
• Their absorption in our intestine is much lower than that of cholesterol.
• Phytosterols interfere with intestinal absorption of cholesterol and facilitate the excretion of cholesterol-containing bile in the feces.
• Daily consumption of phytosterols-enriched foods can lower blood cholesterol concentration.

Cancer-specific

• Supplementation of animals with phytosterols reduced the multiplication of abnormal cells in chemically induced early lesions and tumors (74).
• Evidence of a lower risk of cancer with higher intakes of phytosterols in humans is limited to case-control studies (75).

What we know

• At present, there is not enough evidence to inform whether diets high in phytosterols might reduce the risk of colorectal cancer.

Alcoholic Beverages

What they do

General

• Alcoholic beverages contain ethanol and other ingredients with bioactive properties and potential health effects.
• When consumed in moderation (1-2 drinks/day), alcohol consumption has been associated with beneficial effects on the cardiovascular system.

Cancer-specific

• Even modest intakes of alcohol may increase the risk of cancer (76).
• Alcohol intake is a risk factor for certain cancers of the digestive system and for breast cancer (76, 77).

What we know

• Regular intakes of >3 alcoholic drinks/day (>42 g/day) have been associated with a 25% higher risk of colorectal cancer (78). It is unclear whether lower intakes are also associated with a higher risk of colorectal cancer (78, 79).
• Light alcohol drinking (≤1 drink/day) prior to colorectal cancer diagnosis was associated with lower risks of overall mortality and colorectal cancer-related mortality (when compared to no drinking) (80).

For more information, see the article on Alcoholic Beverages.

Coffee

What it does

General

• Coffee is a complex mixture of carbohydrates, lipids, amino acids, minerals, and other bioactive compounds like caffeine that can influence human health.
• Drinking coffee is associated with lower risk developing type 2 diabetes mellitus and a lower risk of dying from cardiovascular disease.

Cancer-specific

• Some bioactive compounds present in coffee, such as caffeine and a class of phytochemicals called diterpenes, have displayed anticancer activities in experimental studies (81).
• Lower risks of cancer of the oral cavity, uterus, and liver have been consistently reported in coffee drinkers (81, 82).
• There is no relationship between coffee consumption and death from cancer overall (82).

What we know

• Evidence of a reduced risk of colorectal cancer with coffee consumption comes primarily from case-control studies (83-86).
• Consumption of ≥2 cups of coffee (caffeinated or not) may be associated with better survival rate in people diagnosed with stage I-III colorectal cancer (87).

For more information, see the section on Cancer prevention in the article on coffee.

Dairy Products

What they do

General

• Dairy products refer to milk and products derived from milk like yogurt, cheese, and butter. Dairy foods are a good source of energy (protein, fat, and carbohydrates), vitamins (e.g., B vitamins, vitamin E, vitamin D [when fortified]), and minerals (e.g., calcium, magnesium, phosphorus, potassium, sodium, zinc) (88).
• Dairy food consumption plays an important role for bone health across all stages of life by supplying key nutrients (especially calcium, vitamin D, and protein) necessary to build strong bones and limit the occurrence of bone disease and fractures later in life (89).
• Consumption of dairy products is associated with a lower risk of type 2 diabetes mellitus (90, 91). No such associations have been found with risks of hypertension (92) or cardiovascular disease (93, 94).

Cancer-specific

• Dairy products are a major source of conjugated linoleic acid, which has been found to display anticancer activities in experimental studies. The overall nutritional profile of dairy foods may also be important to protect against cancer (88).
• Some evidence points to higher risks of gastric cancer (96), prostate cancer (97), ovarian cancer (98), and non-Hodgkin lymphoma (99) with higher intakes of milk. However, data are too limited and inconsistent, and no causal relationship has been established (100).
• There is no evidence of an association between dairy food consumption and the risks of lung (101, 102), pancreatic (103), breast (104, 105), or endometrial (106) cancers.

What we know

• Higher versus lower intakes of dairy products have been associated with a 20% lower risk of colorectal cancer (107, 108).
• Consumption of specific dairy products, including total and low-fat milk, yogurt, and cheese, has been associated with a lower risk of colorectal cancer. There is no evidence of an association between consumption of either whole milk or cultured (fermented) milk and risk of colorectal cancer (108).

For more information, see the section on colorectal cancer in the Calcium article.

Fish

What they do

General

• Fish are part of a healthy dietary pattern. They are a good source of protein, long-chain omega-3 fatty acids (a type of polyunsaturated fatty acids), vitamins (B₁₂, D), and essential minerals (iron, zinc, selenium, iodine).
• High intakes of fish have been associated with lower risks of cardiovascular disease and cognitive deterioration.

Cancer-specific

• Higher dietary intakes of a number of nutrients provided by fish intake, including omega-3 fatty acids, vitamin D, and zinc, have been associated with lower risks of developing cancer.
• In animal experiments, oral supplementation with omega-3 fatty acids and their derivatives reduced the risk of cancer by triggering mechanisms against inflammation, oxidative stress, and abnormal cell proliferation (12, 13).

What we know

• Evidence from prospective cohort studies suggests an 8% lower risk of colorectal cancer with higher versus lower intakes of fish (110).

Fruit and Vegetables

What they do

General

• Adherence to diets rich in fruit and vegetables has consistently been associated with lower risks of developing chronic diseases, particularly type 2 diabetes mellitus and cardiovascular disease.
• Higher intakes of apples, berries, citrus fruit, cruciferous vegetables, and green leafy vegetables have been associated with a lower risk of dying prematurely.

Cancer-specific

• Daily consumption of five portions (~400 g) of a variety of fruit and non-starchy vegetables is recommended to lower the risk of certain types of cancer (111).
• Micronutrients (e.g., vitamin C) and phytochemicals (e.g., flavonoids in citrus fruit, organosulfur compounds in garlic and cruciferous vegetables) have anticancer properties likely related to their ability to limit carcinogen formation, activation, and/or toxicity, and to prevent abnormal cell multiplication.
• Fruit and vegetables are also a great source of dietary fibers that protect the digestive mucosa from exposure to carcinogens and contribute, through their fermentation in the colon, to the formation of short-chain fatty acids with anti-inflammatory and anticancer activities.

What we know

• There is consistent evidence showing that high intakes of fruit and vegetables are associated with a lower risk of developing colorectal cancer (112-114).
• Limited evidence from case-control studies suggests that high intakes of cruciferous vegetables may be associated with a lower risk of colorectal cancer (71, 72).
• There is no evidence of an association between intakes of garlic and risk of colorectal cancer (115, 116).

For references and more information, see the articles on Fruit and Vegetables, Cruciferous Vegetables, and Garlic.

Healthy Diets

What they do

General

• Healthy dietary plans stress the intake of certain food groups, such as fruit and vegetables, whole grains, nuts and legumes, low-fat dairy products, and lean meat, while playing down the intake of red and processed meats.
• High intakes of red and processed meats, sugar-sweetened beverages, refined grains, potatoes, and desserts usually characterize unhealthy dietary patterns.
• Adherence to a healthy dietary pattern, such as the DASH eating plan or the traditional Mediterranean diet, is associated with improved cardiovascular and overall health (117-119).

Cancer-specific

• High adherence to a Mediterranean-style (120-122) or a DASH-style (123) diet is associated with a lower overall mortality from cancer.

What we know

• The overall evidence points to a reduced risk of colorectal cancer with higher adherence to diets high in fruit and vegetables and low in meats and sweets. However, this association was mainly apparent in case-control studies and not in prospective cohort studies (124).
• Pooled analyses of studies indicate that higher adherence to the Mediterranean (122) or DASH diet is associated with an approximately 20% lower risk of colorectal cancer (125).

For more information about the DASH eating plan, visit the National Institutes of Health website.

Legumes

What they do

General

• Foods from the legume family include beans, peas, lentils, soybeans, and peanuts.
• Legumes are a good source of protein, essential minerals (magnesium, potassium, iron, zinc), vitamins (folate), fiber, and phytochemicals (flavonoids and phytosterols).

Cancer-specific

• Soybeans are a good source of isoflavones, which are structurally similar to mammalian estrogens. The anti-estrogenic properties of isoflavones may be useful to prevent hormonally driven cancers like cancers of the breast and prostate.  
• Legumes are a good source of fiber; higher fiber intake is beneficial to gastrointestinal health and may help prevent cancers of the gastrointestinal tract.

What we know

• There is no consistent evidence to suggest a lower risk of colorectal cancer with higher intakes of legumes, legume fibers, soy products, or isoflavones (66, 113, 114, 126-128) .

For more information, see the section on cancer prevention in the Legumes article.

Nuts

What they do

General

• Nuts are a good source of soluble fiber, phytosterols, polyphenols, mono- and polyunsaturated fatty acids, protein, and certain vitamins (folate, vitamin E) and minerals (calcium, magnesium, potassium).
• Examples of tree nuts include almonds, Brazil nuts, cashews, hazelnuts, macadamia nuts, pecans, pistachios, and walnuts.
• Peanuts are not nuts; they are legumes. However, peanuts are nutritionally similar to tree nuts and offer some of the same health benefits.
• Regular nut consumption (1 ounce at least 5 times per week) is associated with a significantly lower risk of developing or dying from coronary heart disease.

Cancer-specific

• Several nutritional components present in nuts and peanuts — fiber (129), phytochemicals (130-134), micronutrients (135), and mono/polyunsaturated fatty acids (136) — may protect against cancer.
• Nut consumption has been inversely associated with the risk of specific cancer types, including ovarian cancer (137), prostate cancer (137), and non-cardia gastric cancer (138, 139).
• Nut consumption is also associated with a lower risk of premature death by cancer (140).

What we know

• There is little evidence to suggest a lower risk of colorectal cancer with tree nut and peanut consumption (113, 137).
• One prospective cohort study in people who had a stage III colorectal tumor found that higher (vs. lower) nut intake was associated with less risk of tumor recurrence and better survival over a six-year period (141).

For more information, see the section on cancer prevention in the Nuts article.

Red and Processed Meats

What they do

General

• Meat is a good source of protein, vitamins (vitamin A and B vitamins), and minerals (iron, zinc, selenium, phosphorus). The fat content of meat varies across retail cuts of beef, poultry, and other meats, as well as with processing techniques and cooking methods (142).
• Red meat refers to meat of beef, veal, pork, lamb, sheep, horse, and goat. Processed meat usually refers to products made of red meat that are cured, salted, or smoked and contain high amounts of minced fatty tissues (e.g., sausages) (143). Thus, processed meats usually have a higher content of saturated fat, cholesterol, salt (sodium chloride), and nitrates than fresh, unprocessed red meats (144).
• Long-term consumption of red meat, especially if processed, has been associated with higher risks of type 2 diabetes mellitus, cardiovascular disease, and premature death (144).

Cancer-specific

• Several molecules generated during meat processing (e.g., N-nitroso-compounds, polycyclic aromatic hydrocarbons) or when meat is heated at high temperatures (e.g., heterocyclic aromatic amines) are suspected or well-known carcinogens. Other mechanisms involving, for example, the oncogenic effect of heme iron (much more abundant in red than white meat) have been suggested to explain the potential hazards associated with consuming red and processed meat (144).
• Limited evidence suggests that consuming large amounts of red and/or processed meat is associated with higher risks of esophageal, stomach, liver, and bladder cancer (143, 144).

What we know

• High consumption of processed meat is associated with a high risk of colorectal cancer (113, 114, 145).
• Recent pooled analyses also suggest that high intake of red meat is a risk factor for colorectal cancer (113, 114). Limited evidence indicates that high intakes of beef and lamb, but not pork and poultry, are associated with a higher risk of colorectal cancer (146).

Tea

What it does

General

• Tea is an infusion of the leaves of the Camellia sinensis plant and includes white, green, oolong, and black teas. This summary does not discuss herbal teas, which are infusions of herbs or plants other than Camellia sinensis.
• Tea contains a number of bioactive substances, including caffeine, fluoride, and flavonoids (primarily flavan-3-ols), which may exert health effects. Daily consumption of 2-4 cups of tea is associated with lower risks of type 2 diabetes and cardiovascular disease (147).

Cancer-specific

• Tea is particularly rich in catechins (flavan-3-ol monomers), a subclass of flavonoids with antioxidant properties that could protect in particular the epithelium of the digestive tract against oxidative injury, block the activation of carcinogen, and interfere with cancer cell multiplication (148). 
• Tea consumption has not been associated with lower risks of any cancer types except cancers of the oral cavity (149).

What we know

• There is no consistent evidence to suggest that higher intakes of tea are associated with a reduced risk of developing colorectal cancer (114, 150, 151).

For more information, see the section on cancer prevention in the Tea article.

Whole Grains

What they do

General

• Whole grains are the seeds of plants belonging to the grass family. The grass family includes wheat, rice, maize (corn), barley, oats, and rye.
• Whole-grain products contain all three layers of the seed: bran, endosperm, and germ.
• In contrast to whole grains, refined grains are stripped of the bran and germ layers. Some essential micronutrients (thiamin, riboflavin, niacin, iron) are sometimes added back to the grain after the refining process, producing what is known as an "enriched grain."

Cancer-specific

• Whole grains contain several nutrients and dietary factors that are associated with cancer risk reduction.

• The fermentation of dietary fiber in the large intestine produces short-chain fatty acids with anticancer properties. Fiber also protects the digestive tract by diluting carcinogens in the fecal bulk and speeding up transit (154).
• Antioxidants (e.g., polyphenols, carotenoids, ferulic acid, vitamin E, and minerals like iron, zinc, copper, and selenium) protect tissues against oxidative damage that increases the risk of cancer (154).
• Consumption of fiber-rich whole grains improves glucose and lipid metabolism. Metabolic disorders like obesity and diabetes are risk factors for colorectal cancer (155).

• High intakes of whole grains have been associated with a lower risk of death by cancer (156-158).

What we know

• Consuming about three servings (90 g) of whole-grain products per day is associated with a nearly 20% lower risk of colorectal cancer (114, 126).

For general information, see the Whole Grains article.

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