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.

DEFINITIONS
Anal canal - the most terminal portion of the large intestine, between the rectum and the anus
Cecum - the first part of the large intestine, connecting the small intestine with the ascending colon
Colonic crypts - invaginations that open into the surface epithelium. Stem cells in the lowest (basal) part of crypts multiply and acquire specific functions, thereby ensuring the renewal of mature epithelial cells.
Electrolytes - charged particles (called ions) that are constituents of all living cells and tissues. Major electrolytes in the body include sodium, potassium, magnesium, calcium, chloride, bicarbonate, and phosphate.
Familial adenomatous polyposis - a hereditary syndrome characterized by the formation of many polyps in the colon and the rectum. Some of the colorectal polyps (adenomas) may become cancerous.
Polyps - a benign (non-cancerous) mass of cells that forms on the inside of a hollow organ, such as the colon
Rectum - the portion of the large intestine, connecting the sigmoid colon to the anal canal. The rectum stores stool until it is evacuated from the body.
Villi - small finger-like projections into the lumen of the small intestine

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).
DEFINITION
Incidence - proportion of new cases of a disease in a given population at risk over a specific period of time

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.

DEFINITIONS
Adenoma - benign tumor of glandular tissue like the colorectal mucosa. The terms adenoma, adenomatous polyp, and polyp are often used interchangeably
Carcinoma - a type of malignant tumor (cancer) of epithelial origin. Adenocarcinoma is a subtype of carcinoma that developed from glandular tissue. Most colorectal cancers are adenocarcinomas
Epigenetic anomalies - refers to anomalies that do not involve alterations of the DNA sequence, as opposed to genetic anomalies, e.g., abnormal DNA methylation

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).

DEFINITION
Adenocarcinoma - a type of malignant tumor derived from a benign tumor (adenoma) of glandular origin

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.

DEFINITION
Colonoscopy - procedure that consists of looking inside the colon and rectum with the help of a flexible instrument (colonoscope) that has a light and small video camera on the end. The colonoscope is introduced into the rectum and colon through the anus.

Nutrition Research

DEFINITIONS
Test tube (in vitro) experiment - a research experiment performed in a test tube, culture dish, or other artificial environment outside of a living organism; in vitro is a Latin phrase meaning ‘in glass’
Animal experiment - a research experiment performed in a laboratory animal; many different animal species are studied in the laboratory, including terrestrial (land), aquatic (water), and microscopic animals
Observational study - a human research study in which no experimental intervention or treatment is applied, and participants are simply observed. Observational studies include, among others, case-control and prospective cohort studies. Observational studies can be used to examine whether there may be a relationship between an exposure and an outcome, but they cannot inform whether there is a causal relationship.
Randomized controlled trial - a human research study in which participants are randomly assigned to receive an active treatment or an inert (control or placebo) treatment. Randomized controlled trials are powered to examine whether there is a cause-and-effect relationship between an exposure and an outcome. This type of study is often used to test the efficacy of an active treatment on a specific outcome compared to a control.
Placebo - a substance without therapeutic effect (i.e., a chemically inert substance)

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).
DEFINITIONS
Adjunct to chemotherapy - also called add-on therapy, it refers to a treatment that is given in addition to the standard-of-care for chemotherapy in order to enhance efficacy of treatment
Chemotherapy - literally, treatment with drugs. Commonly used to describe the use of drugs in the treatment of cancer.
Oxidative stress - refers to the condition in which the effects of pro-oxidants (e.g., reactive oxygen species) exceed the ability of antioxidant systems to neutralize them
Trans fatty acids - trans, unsaturated fatty acids are naturally occurring in small amounts in meat and milk but are produced in large amounts during the industrial processing of vegetable and fish oils (hydrogenated or partially hydrogenated oils). The trans configuration of double bonds in unsaturated fatty acids contrasts with the naturally occurring cis configuration.

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.

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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).
HIGHLIGHT

Fiber is identified as a shortfall nutrient of public health concern in the 2015-2020 Dietary Guidelines for Americans. Intake recommendations and good sources of dietary fiber can be found in the Fiber article.

Some suggestions for increasing fiber intake:

  • Eat at least five servings of fruit and vegetables daily.
  • Substitute whole grains for refined grains.
  • Eat oatmeal, whole-grain cereal, or bran cereal for breakfast.
  • Eat beans, split peas, or lentils at least once weekly.
  • Substitute nuts or popcorn for less healthful snacks like potato chips or candy.

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

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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).
DEFINITIONS
Cell-signaling pathways - refers to cascades of events leading to changes within a cell in response to changes in a cell’s environment
Tumor suppressor - refers here to a protein that functions to protect cells from progressing in the path to cancer. The expression or function of tumor suppressors is often disrupted in cancer cells.

For general information about calcium, see the Calcium article.

Calcium Flashcard. Main Functions: 1) structural component of bones and teeth, 2) regulates nerve transmission and muscle contraction, 3) helps maintain a healthy blood pressure, and 4) helps maintain acid-base balance in the blood. Good Sources: dairy (yogurt, milk, cheese), plain yogurt, 8 ounces or 1 cup = 415 mg; sardines (canned) 1 can or 3.75 ounces = 351 mg; green leafy vegetables (kale, bok choy), collard greens (cooked), one-half cup = 300 mg; mg= milligrams. Daily Recommendation: 1,000 mg for men 19-70 years, 1,200 mg for men 71+ years; 1,000 mg for women 19-50 years, 1,200 mg for women 51+ years. Special Notes: 1) Many Americans do not consume enough calcium. Just 3 servings of dairy per day would meet the recommendation. For those who don't consume dairy, calcium-fortified juices, cereals, and milk alternatives are a good substitute. 2) To maximize absorption from supplements, take no more than 500 mg at a time.

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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
  • A poor folate status (21), as well as certain genetic variations in the metabolism of folate (22), has 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).
HIGHLIGHT
Inadequate folate status in early pregnancy increases the risk of specific birth defects called neural tube defects (NTDs). In 1998, the US mandated that all refined grain products be fortified with folic acid; this has greatly reduced the occurrence of NTDs. Worldwide, 82 other countries mandate folic acid fortification of at least one refined grain (27).
DEFINITIONS
Methylation reaction - this type of reaction consists of adding a methyl group (-CH3) to a given substrate
Neural tube defects - birth defects arising from the improper closer of the neural tube (the precursor of the brain and spinal cord) of the embryo, which occurs in the 4th week following conception
Recurrent tumor - refers to a tumor that comes back in the same place or close by, after a period of time during which it could not be detected
Sessile serrated adenomas - a type of polyp that can transform into a subtype of colorectal cancer called serrated adenocarcinoma
Thymine - a base that is combined with a sugar and a phosphate group to form one of four building blocks of DNA. The other bases are adenine, guanine, and cytosine. Thymine is replaced by uracil in RNA.

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

Folate Flashcard. Main Functions: 1) required for DNA synthesis, 2) supports cell growth and repair, 3) helps prevent neural tube defects. Good Sources: legumes (beans, peas, lentils), lentils (cooked) one-half cup = 179 micrograms dietary folate equivalents (DFE); green leafy vegetables (kale, spinach), spinach (cooked) one-half cup, 131 micrograms DFE; fortified food and supplements, sliced bread (enriched), 1 slice, 84 micrograms DFE. Daily Recommendation: 400 micrograms DFE for adults, 600 micrograms DFE for pregnant women. Special Notes: 1) Folate is a general term that refers to both natural folates in food and folic acid, the synthetic form used in supplements and fortified food. 2) DFE = a unit of measure that accounts for differences in the absorption of naturally occurring food folate and synthetic folic acid. 3) To reduce the risk of neural tube defects, all women capable of becoming pregnant should consume 400 micrograms of folic acid daily in addition to the folate obtained from a varied diet. 4) Very high-dose folic acid supplementation (5,000 micrograms) can mask a vitamin B12 deficiency, specifically signs of nerve damage.

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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)
DEFINITIONS
Antioxidant enzymes - enzymes that contribute to neutralizing atoms or molecules capable of damaging essential cell constituents
Cytochromes - a family of enzymes involves in electron transfer
Electron - a stable atomic particle with a negative charge
Hydroxyl radical - a type of reactive oxygen species that can be neutralized by antioxidants
Nitrosamines - cancer-causing compounds produced from nitrites and amines derived from proteins either during meat processing or under the strongly acidic condition of the stomach

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

Iron Flashcard. Main Functions: 1) Helps make healthy red blood cells that transport oxygen throughout the body, 2) Critical for normal immune function, 3) Structural component of hundreds of essential molecules, and 4) Assists antioxidant enzymes. Good Sources: There are two forms of dietary iron: heme iron and nonheme iron. Heme iron is found in red meat, poultry, and fish. 3 ounces of red meat contains 2.3 mg of heme iron. Nonheme iron is found in lentils, vegetables, and fortified food. One-half cup of cooked lentils contains 3.3 mg of nonheme iron. Daily Recommendation: 8 mg for adult men, 18 mg for women 19-50 years, 8 mg for women 51 years and older. Special Notes: 1) Heme iron is better absorbed than nonheme iron; the absorption of nonheme iron is enhanced by vitamin C. 2) National dietary surveys indicate that iron is underconsumed by adolescent and premenopausal females. 3) The Daily Recommendation for iron is significantly increased during pregnancy (from 18 to 27 mg/day), yet dietary surveys indicate that the average intake among pregnant women in the US is 15 mg/day. 4) Iron is efficiently recycled by the body. Premenopausal women have higher requirements due to menstrual losses.

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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).
DEFINITION
ATP - acronym for adenosine triphosphate; an important compound for the storage of energy in cells, as well as the synthesis of DNA

Magnesium Flashcard. Main Functions: 1) Structural component of bones and teeth, 2) Regulates nerve transmission and muscle contraction, and 3) Assists in hundreds of essential cellular reactions. Good Sources: Whole Grains (wheat, oats, barley), brown rice, cooked, 1 cup = 86 mg; Green Leafy Vegetables (Swiss chard, spinach), spinach (boiled), 1 cup = 157 mg; Nuts (hazelnuts, cashews), almonds, 1 ounce or 23 almonds = 77 mg. Daily Recommendation: 400 mg for men 19-30 years, 420 mg for men 31 years and older; 310 mg for women 19-30 years, 320 mg for women 31 years and older. Special Notes: 1) Most people consume too little magnesium. 2) The Tolerable Upper Intake Level (UL) for magnesium is 350 mg/day from supplements. The UL does not apply to naturally occurring magnesium from food.

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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).
DEFINITIONS
Antioxidant enzymes - enzymes that contribute to neutralizing atoms or molecules capable of damaging essential cell constituents
Methylation reaction - a type of reaction that consists of adding a methyl group (-CH3) to a given substrate

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

Riboflavin (vitamin B2) Flashcard. Main Functions. (1) helps convert food into useable energy, and (2) assists several antioxidant enzymes. Good Sources. Dairy Products (milk, yogurt, cheese), milk (nonfat), 8 ounces, 0.45 mg; Meat (chicken, beef, fish), salmon, 3 ounces, 0.13 mg; Egg (1 large), 0.26 mg. A 3-ounce serving of meat or fish is about the size of a deck of cards. Daily Recommendation. 1.3 mg for men, 1.1 mg for women. Special Notes. (1) riboflavin is easily destroyed upon exposure to light. (2) Low-dose riboflavin supplementation may lower blood pressure in individuals with a genetic mutation in MTHFR, and enzyme involved in folate metabolism.

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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).
DEFINITIONS
Antioxidant enzymes - enzymes that contribute to neutralizing atoms or molecules capable of damaging essential cell constituents
Oxidative damage - damage caused to large molecules (i.e., carbohydrates, protein, fat, DNA) by the presence of reactive oxygen species

Selenium Flashcard. Main Functions: (1) Assists antioxidant enzymes, (2) Needed for production of thyroid hormone, which helps maintain body temperature and basal metabolic rate, and (3) Supports immune function. Good Sources: Meat, nuts, seafood, and whole grains are good sources of selenium. Meat (beef, chicken, pork), beef, 3 ounces, 30.6 micrograms; Nuts (Brazil nuts, sunflower seeds), sunflower sees, one-fourth cup, 18.6 micrograms; Seafood (tuna, clams, shrimp), tuna, 3 ounces, 92.0 micrograms. Daily Recommendation: 55 micrograms for adults. Special Notes: (1) The selenium content of plants and grains varies greatly. (a) Food selenium content is influenced by the selenium content of the soil in which it was grown. (b) Some plants accumulate selenium to a greater extent, including garlic, Brazil nuts, and Brassica vegetables (broccoli, Brussel sprouts, cabbage, cauliflower, kale). (c) A single serving of Brazil nuts (6 nuts) is above the tolerable upper intake level (UL) of 400 micrograms per day. (2) Most people in the US consume enough selenium to meet the recommendation.

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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).
HIGHLIGHT
Consumption of high doses of vitamin A (in the form of retinol or retinyl esters) can be highly toxic and is unlikely to reduce the risk of colorectal cancer. Vitamin A supplements should be reserved for undernourished populations and individuals with evidence of vitamin A deficiency.
DEFINITIONS
Lymphomas - a group of blood cancers developing from specific white blood cells called lymphocytes
Neuroblastoma - cancer arising from nerve cells of the central or peripheral nervous system
Tolerable upper intake level (UL) - the highest level of daily intake of a given nutrient that likely poses no risk of adverse effects in almost all individuals of a specific age. The UL for vitamin A in adults is set at 3 mg/day of retinol equivalents (10,000 IU/day).

Vitamin A (retinol) Flashcard. Main Functions: 1) Essential for site, dim-light adaptation, and color vision; 2) Supports reproductive health for both men and women; 3) Required for proper immune function; 4) Influences cell growth and development. Good Sources: There are two forms of dietary vitamin A: preformed vitamin A from animal products and provitamin A carotenoids from fruit and vegetables. Preformed Vitamin A: cod liver oil, 1 teaspoon = 1,350 micrograms retinol activity equivalents (RAE), 1 large egg = 80 micrograms RAE. Provitamin A (yellow & orange fruit & vegetables), sweet potato (baked), 1 cup = 1,922 micrograms RAE. Daily Recommendation: 900 micrograms RAE for men and 700 micrograms RAE for women. Special Notes: 1) RAE = a unit of measure for the vitamin A content of food. It reflects the amount of active vitamin A provided by the different types of food sources. 2) It is possible to ingest too much vitamin A (retinol). The Tolerable Upper Intake Level (UL) is 3,000 micrograms RAE of retinol/day. 3) There is no UL for provitamin A carotenoids because the liver controls their conversion to retinol.

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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 could be protective against any cancer, including colorectal cancer (38).

Vitamin B6 Flashcard. Main Functions: 1) helps convert food into energy, 2) helps make red blood cells, 3) helps maintain normal levels of homocysteine in the blood. Good Sources: Fish (slamon, tuna, halibut), wild salmon, 3 ounces, 0.5-0.8 mg; poultry (turkey, chicken, duck), light-meat turkey (cooked), 3 ounces = 0.7 mg; nuts (hazelnuts, walnuts) pistachio nuts, 1 ounce or 47 pistachios = 0.5 mg. Daily Recommendation: 2 mg for all adults. Special Notes: 1) The Daily Recommendation listed is specific to the LPI based on extensive review of the scientific evidence. The Institute of Medicine's Recommended Dietary Allowance (RDA) is 1.3 mg/day for adults 19-50 years, 1.7 mg/day for men 51 years and older, and 1.5 mg/day for women 51 years and older. 2) In the US, vitamin B6 is added back to refined grains. Therefore, enriched products are also a source of vitamin B6. 3) Excessive supplementation of vitamin B6 (more than 100 mg/day) can cause nerve damage and skin lesions.

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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.
DEFINITIONS
Nitrosamines - cancer-causing compounds produced from nitrites and amines derived from proteins either during meat processing or under the strongly acidic condition of the stomach
Oxidative damage - damage caused to large molecules (i.e. carbohydrates, protein, fat, DNA) by the presence of reactive oxygen species
Reactive oxygen species - highly reactive chemicals, containing oxygen, that react easily with other molecules, resulting in potentially damaging modifications

Vitamin C (ascorbic acid) Flashcard. Main Functions: 1) Antioxidant defense, 2) Enhances immune function, 3) Needed to make collagen, carnitine, and the neurotransmitters serotonin and norepinephrine. Good Sources: Fruit, 1 medium-sized kiwifruit = 90 mg; strawberries, 1 cup whole, 85 mg; Vegetables (broccoli, kale, tomatoes), sweet red pepper (one-half cup, chopped) = 95 mg. Daily Recommendation is 400 mg for all adults. Special Notes: 1) Heat destroys vitamin C. Try to eat fresh foods and cook by steaming, microwaving, or stir-frying. 2) Vitamin C in food is identical to vitamin C in supplements. 3) The Daily Recommendation listed is specific to the LPI based on extensive review of the scientific evidence. The Institute of Medicine's Recommended Dietary Allowance (RDA) is 90 mg/day for men and 75 mg/day for women.

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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).
DEFINITION
Homeostasis - a state of equilibrium in biological systems. Dynamic mechanisms deal with changes in internal and external environments to ensure constancy of physiological conditions.

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

Vitamin D (calciferol) Flashcard. Main Functions: 1) Facilitates absorption of calcium and phosphorus, 2) Promotes bone health, 3) Required for proper immune function, and 4) Influences cell growth and development. Good Sources: Fatty Fish (salmon, mackerel, sardines), pink canned salmon, 3 ounces = 465 IU or 11.6 micrograms; Canned mackerel, 3 ounces = 211 IU for 5.3 micrograms; Fortified food, low-fat milk, vitamin D fortified, 8 ounces = 98 IU or 2.5 micrograms. Daily Recommendation: 600-1,000 IU (15-25 micrograms) for chldren and adolesents (4-18 years), because vitamin D is scarcely found in food, it may be necessary to take supplements. 2,000 IU or 50 micrograms for all adults, this amount applies to supplemental vitamin D, which is recommended in addition to vitamin D from a mixed diet. Special Notes: 1) The Daily Recommendation listed is specific to the LPI based on extensive review of the scientific evidence. The Institute of Medicine's Recommended Dietary Allowance (RDA) is 600 IU (15 micrograms)/day for males and females who are 4-70 years old, and 800 IU (20 micrograms)/day for all adults over 70. 2) Vitamin D is considered a "Nutrient of Public Health Concern" because underconsumption is linked to adverse health outcomes. 3) More than 90% of Americans do not meet the dietary requirement for vitamin D. 4) our bodies make vitamin D upon skin exposure to UVB radiation from the sun. Darker skin color, northern latitude, and older age impede the amount of vitamin D produced.

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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).

Zinc Flashcard. Main Functions: 1) Assists in the production of hemoglobin, the oxygen-carrying component of red blood cells; (2) Critical for normal immune function; and (3) Structural component of hundreds of essential molecules. Good Sources: seafood (oysters, crab), 6 medium-sized oysters (steamed) = 49.9 mg; meat (beef, dark meat, pork), rib eye steak (grilled) 3 ounces = 5.9 mg; beans (chickpeas, black beans), black beans (canned) one-half cup = 0.7 mg. Daily Recommendation; 11 mg for men and 8 mg for women. Special Notes: (1) Some dietary factors affect zinc absorption: (a) Phytates and fiber in whole grains and beans inhibit absorption, and (b) Animal-based protein enhances absorption. (2) National dietary surveys indicate that most Americans meet the dietary requirement for zinc.

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HIGHLIGHT
Test tube experiments are performed on isolated cells, grown in a laboratory, that are exposed to high concentrations of a test compound. It is important to keep in mind that test tube and animal experiments provide valuable information but differ from human trials in many ways. The outcome may differ for humans ingesting dietary or supplemental versions of the experimental agent.

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).
DEFINITIONS
Anticancer activities - a set of actions that contribute to decreasing the chance for abnormal cells to multiply and spread
Oxidative damage - damage caused to large molecules (i.e., carbohydrates, protein, fat, DNA) by the presence of reactive oxygen species

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

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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).
DEFINITIONS
Bioavailability - the fraction of ingested compound that reaches the circulation and is transported to the site of action
Familial adenomatous polyposis - a hereditary syndrome characterized by the formation of many polyps in the colon and the rectum. Some of the colorectal polyps (adenomas) may become cancerous
NSAIDs - acronym for nonsteroidal anti-inflammatory drugs; NSAIDs reduce pain and inflammation and are prescribed for the symptomatic relief of people affected by chronic inflammatory conditions.
Pilot study - a preliminary study performed to test specific parameters and decide whether a research project could be scaled up.

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

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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).
DEFINITIONS
Free radicals - atoms or molecules (with ≥1 unpaired electron) that are highly reactive and can potentially damage large molecules like DNA and lipids; e.g., reactive oxygen species
Carcinogen - cancer-causing agent

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

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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).
DEFINITIONS
Adjunct therapy - also called add-on therapy, it refers to a treatment that is given in addition to a standard-of-care protocol in order to enhance efficacy of treatment
Carcinogen - cancer-causing agent
Glucosinolates - sulfur-containing compounds present in cruciferous vegetables. When raw cruciferous vegetables are chopped, glucosinolates are broken down to release isothiocyanates.
Oxidative damage - damage caused to large molecules (i.e., carbohydrates, protein, fat, DNA) by the presence of reactive oxygen species
HIGHLIGHT
Cruciferous vegetables are usually cooked before consumption such that only a small fraction of glucosinolates is broken down to release isothiocyanates. Chop raw cruciferous vegetables, let them sit for several minutes to maximize the formation of isothiocyanates, and steam them for no more than 5 minutes.

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

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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.

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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).
HIGHLIGHT
  • 1 standard alcoholic drink contains 14 g of pure alcohol, which is equivalent to:
    • 12 fluid ounces (fl oz) of beer (~5% of alcohol);
    • 8.5 fl oz of malt liquor (~9% of alcohol);
    • 5 fl oz of wine (~12% of alcohol);
    • 1.5 fl oz of distilled spirit (liquors; ~40% of alcohol)
  • Alcohol is metabolized differently in women and men such that recommendations have a lower threshold for women
  • No alcohol should be consumed by:
    • Pregnant women or women intending to become pregnant;
    • People taking over-the-counter or prescribed medications with the potential for adverse interactions with alcohol;
    • People planning to drive or engage in activities requiring coordination and alertness;
    • Recovering alcoholics;
    • Anyone aged <21 years (according to US alcohol legislation).

For more information, see the article on Alcoholic Beverages.

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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).
HIGHLIGHT
Consuming ≤3 cups of filtered coffee daily is unlikely to pose any risk to health in men and in women who are not pregnant. Pregnant women should limit their intake to 1 cup/day, and those breast-feeding should limit coffee intake to 2-3 cups/day.
DEFINITION
Phytochemicals - biologically active molecules found in plants

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

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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).
HIGHLIGHT
Replacing dairy products with calcium-replacement foods (e.g., bony fish, calcium-set tofu, leafy greens, and fortified beverages [e.g., soy- and almond-based beverages, rice drink, and orange juice]) alter the nutritional profile of one’s diet. For example, substituting soy drinks for low-fat dairy will supply less protein, fat, magnesium, phosphorus, and potassium (95).

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).
HIGHLIGHT
Most recommended healthy dietary patterns include the consumption of three servings of dairy foods per day in order to meet the recommended dietary allowance (RDA) for calcium (10, 109). The 2015-2020 Dietary Guidelines for Americans recommend to pick fat-free or low-fat dairy alternatives (10), although be aware that fat may be replaced by sugars in some of these products.
DEFINITIONS
Anticancer activities - a set of actions that contribute to decreasing the chance for abnormal cells to multiply and spread
Recommended Dietary Allowance (RDA) - the average daily dietary intake level of a nutrient sufficient to meet the requirements of nearly all healthy individuals in a specific life stage and gender group

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

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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).
DEFINITIONS
Cognitive - refers to the processes of cognition, i.e., brain functions like attention, memory, planning, developing strategies, and problem solving
Oxidative stress - a situation in which the production of reactive oxygen species exceeds the ability of an organism to eliminate or neutralize them
HIGHLIGHT
The 2015-2020 Dietary Guidelines for Americans recommend consuming at least 8 ounces of seafood based on a 2,000-calorie diet. Pregnant and breast-feeding women are encouraged to consume 8-12 ounces per week of a variety of seafood from choices that are low in mercury. See the US Food and Drug Administration’s website for detailed advice on fish consumption.

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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).
HIGHLIGHT
Several initiatives and resources, including Fruits and Veggies on the Go, ChooseMyPlate, 2015-2020 Dietary Guidelines for Americans, and the Intake Recommendations section of the article on Fruit and Vegetables, have been developed to help people include more fruit and vegetables in their daily meals and make healthier food choices.
DEFINITIONS
Carcinogen - a cancer-causing compound
Flavonoids - phenolic compounds widely found in fruit and vegetables; citrus fruit (e.g., oranges, lemons, grapefruit) are rich in a subclass of flavonoids called flavanones
Organosulfur compounds - sulfur-containing molecules. The two main classes of organosulfur compounds found in whole garlic cloves are called L-cysteine sulfoxides and γ-glutamyl-L-cysteine peptides. Organosulfur compounds found in cruciferous vegetables are called isothiocyanates.
Phytochemicals - biologically active molecules found in plants

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

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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).
HIGHLIGHT
The 2015-2020 Dietary Guidelines for Americans provides recommended amounts of foods from each food group corresponding to either a healthy US-style diet (appendix 3), a healthy Mediterranean-style diet (appendix 4), or a healthy vegetarian diet (appendix 6).
DEFINITION
DASH - acronym for dietary approaches to stop hypertension. This balanced eating plan was initially developed to reduce one’s risk of high blood pressure through lowering salt intake.

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

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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.

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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).
HIGHLIGHT
  • Nuts are packed with healthy fats, and therefore, calories.
    • 1 ounce of nuts contains approximately 160 kcal and 14-19 g of fat (mainly mono- and polyunsaturated fatty acids)
  • 1 ounce of nuts equals approximately: 24 almonds, 8 medium Brazil nuts*, 18 medium cashews, 12 hazelnuts, 12 macadamia nuts, 15 pecan halves, 47 pistachios, 14 walnut halves, and 35 peanuts.
  • It is recommended to substitute nuts for sources of saturated fat and junk food.

*Depending on growth conditions, a single Brazil nut could contain an extremely high amount of selenium. 

DEFINITIONS
Inverse association - a relationship between two variables in which they move in opposite directions
Phytochemicals - biologically active molecules found in plants
Tumor recurrence - refers to a tumor that comes back in the same place or close by, after a period of time during which it could not be detected

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

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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).
HIGHLIGHT
The International Agency for Research on Cancer (IARC) identified red meat and processed meat as (potential) carcinogenic hazards to humans. See the IARC monographs on red meat and processed meat.
HIGHLIGHT

Reducing the consumption of red and processed meat in high-consuming countries is generally recommended for both environmental and health concerns. Guidelines from the American Cancer Society suggest to reduce red and processed meat consumption by (9):

  • Limiting the consumption of bacon, sausage, luncheon meats, and hot dogs
  • Choosing fish, poultry, or beans as an alternative to red meat
  • Opting for lean cuts and eating smaller portions of red meat
  • Preparing meat, poultry, and fish by baking, broiling, or poaching rather than frying or charbroiling
DEFINITION
Carcinogen - cancer-causing agent
Oncogenic effect - ability to cause the development of a tumor

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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).
HIGHLIGHT
Consuming very hot beverages (including very hot tea, i.e., >65°C or >149°F) may damage the cells lining the upper digestive tract and specifically increase the risk of esophageal (152) and stomach (153) cancers.

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

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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).
HIGHLIGHT

The 2015-2020 Dietary Guidelines for Americans recommend consuming a minimum of three servings of whole-grain products daily.

Examples of one serving of whole grains:

  • 1 slice of whole-grain bread
  • ½ whole-grain English muffin, bagel, or bun
  • 1 ounce of ready-to-eat whole-grain cereal
  • ½ cup of oatmeal, brown rice, or whole-wheat pasta (cooked)
  • 5-6 whole-grain crackers
  • 1 tortilla (6” diameter)
  • 1 pancake (5” diameter)
DEFINITIONS
Carcinogen - cancer-causing agent
Oxidative damage - damage caused to large molecules (i.e., carbohydrates, protein, fat, DNA) by the presence of reactive oxygen species

For general information, see the Whole Grains article.

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