Overview of cancer prevention

INTRODUCTION — Both screening and prevention can reduce mortality from many cancers. Screening detects abnormalities before they are clinically apparent, allowing for intervention either before cancer develops or at an early stage, when treatment is most often effective. Prevention strategies focus on modifying environmental and lifestyle risk factors that promote cancer. Despite a robust knowledge of what factors decrease cancer risk, implementation of cancer prevention lags [1,2].

This topic reviews the major modifiable cancer risk factors and briefly addresses cancer chemoprevention. More detailed discussion of prevention strategies for specific cancers can be found elsewhere:

●(See "Chemoprevention strategies in prostate cancer".)

●(See "Factors that modify breast cancer risk in women".)

●(See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)

●(See "Epidemiology and risk factors for colorectal cancer".)

The roles of physical activity, dietary patterns, and weight in cancer survivors are discussed separately. (See "The roles of diet, physical activity, and body weight in cancer survivors".)

GENERAL LIFESTYLE RECOMMENDATIONS — Lifestyle factors have been linked to a variety of malignancies, including those common across the globe, such as lung, colorectal, prostate, and breast cancer [3-6]. While multiple cancer risk factors have been identified, tobacco use, excess weight, poor diet, and physical inactivity have been implicated in the majority of cancer deaths in the United States and worldwide [7,8]. The Global Burden of Disease study estimated that in 2019, 50.6 percent of worldwide cancer deaths in males, and 36.3 percent of those in females were attributable to behavioral, environmental and occupational, or metabolic risk factors [9]. Smoking was the leading risk factor for all adults, while other important risk factors included alcohol use, high body mass index, and unsafe sex.

Our general lifestyle recommendations include:

●Avoid tobacco

●Be physically active

●Maintain a healthy weight

●Eat a diet rich in fruits, vegetables, and whole grains and low in saturated/trans fat, red meat, and processed meat

●Limit alcohol (zero is best)

●Protect against sexually transmitted infections; this includes vaccination against human papillomavirus (HPV)

●Protect against the sun and avoid tanning beds

●Get regular screening for breast, cervical, colorectal, and lung cancer (if applicable based on smoking history)

INFECTIONS — It is estimated that 13 percent of all new cancers worldwide are due to infections [10]. Viruses may increase cancer risk through cellular transformation, disruption of cell cycle control, increased cell turnover rates, and immune suppression [11]. Multiple links between infectious agents and cancer have been established:

●Human papillomavirus (HPV) with cervical and other anogenital cancers as well as squamous cell cancers of the head and neck [12] (see "Virology of human papillomavirus infections and the link to cancer" and "Epidemiology, staging, and clinical presentation of human papillomavirus associated head and neck cancer")

●Hepatitis B virus (HBV) and hepatitis C virus (HCV) with hepatocellular carcinoma [13] (see "Epidemiology and risk factors for hepatocellular carcinoma")

●Human T-cell lymphotropic virus type 1 (HTLV-1) with adult T-cell leukemia [14] (see "Treatment of large granular lymphocyte leukemia")

●HIV with Kaposi sarcoma as well as with non-Hodgkin lymphoma [15] and with multiple non-acquired immunodeficiency syndrome (AIDS)-defining malignancies [16] (see "HIV infection and malignancy: Epidemiology and pathogenesis")

●Human herpes virus 8 (HHV-8) with Kaposi sarcoma and primary effusion lymphoma [17,18] (see "Human herpesvirus-8 infection")

●Epstein-Barr virus (EBV) with Burkitt lymphoma [17] (see "Pathobiology of Burkitt lymphoma")

●The bacterium Helicobacter pylori with gastrointestinal malignancies including gastric cancer [19] and mucosa-associated lymphoid tissue (MALT) lymphomas (see "Association between Helicobacter pylori infection and gastrointestinal malignancy")

●Liver flukes with cholangiocarcinoma and hepatocellular carcinoma [20] (see "Liver flukes: Clonorchis, Opisthorchis, and Metorchis")

Interventions to decrease risk from infections — The majority of infections associated with cancer are due to viruses that are spread through contact with infected blood or body fluids. Strategies to prevent such transmission include safer sexual practices, use of sterile disposable needles for a single patient in health care settings, needle exchange programs, regulation of tattooing, continued screening of blood, organ, and semen donors, and the development of artificial blood products. (See "Prevention of sexually transmitted infections" and "Sexual development and sexuality in children and adolescents", section on 'Develop risk-reduction strategies'.)

For some viruses, specific interventions are available to either prevent infection or delay progression to cancer after infection:

●HPV vaccination is recommended for all children, as well as for young women and young men who were not vaccinated during childhood. Additionally, cervical cancer screening has dramatically reduced the incidence of cervical cancer where screening is widely available [21]. (See "Human papillomavirus vaccination" and "Screening for cervical cancer in resource-rich settings".)

●HBV vaccination for adults at high risk of HBV infection to reduce viral infection and subsequent hepatocellular carcinoma. (See "Hepatitis B virus immunization in adults".)

●HCV screening is recommended in all adults ages 18 to 79 years. This is a one-time screening for most adults and periodic screening for those at high risk, such as patients with a history of injection drug use [22].

●Pre-exposure prophylaxis (PrEP) can significantly lower the risk of HIV infection in high-risk groups, and retroviral therapy for HIV infection has greatly altered the course of disease and associated cancers. Antiretroviral therapy (ART) has been shown to reduce the incidence of AIDS-related lymphoma [23]. (See "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach".)

●Decreasing the hepatitis B viral load by treatment with interferon or nucleoside/tide analogues in patients with chronic hepatitis B infection was associated with a decreased risk for hepatoma [24,25]. (See "Hepatitis B virus: Overview of management".)

●Excess alcohol use may play a role in cancer development in patients with chronic HBV and HCV infections and should be avoided. Preliminary data suggest that antiviral therapy may reduce the risk of cancer in patients with chronic HCV infections, with reduction of HCV RNA, but the long-term effect of antiviral therapy on cancer risk is not known [26].

TOBACCO USE — Tobacco use is the most important preventable causes of cancer and accounts for 21 percent of total cancer deaths worldwide [27] and 30 percent of all cancer-related deaths in the United States [28]. Approximately one-half of all smokers die of a tobacco-related disease, and adult smokers lose an average of 13 years of life due to tobacco use [28,29]. (See "Cigarette smoking and other possible risk factors for lung cancer".)

Smoking is the strongest risk factor for lung cancer, increasing risk 10- to 20-fold [30,31]. Smoking is also implicated as a causative factor for leukemia as well as cancers of the oral cavity, nasal cavity, paranasal sinuses, nasopharynx, larynx, esophagus, pancreas, liver, stomach, cervix, kidney, large bowel, and bladder [32,33]. Studies also suggest that smoking is associated with increased incidence of breast cancer as well as prostate cancer, particularly in African American individuals [34-38].

Tobacco acts on multiple stages of carcinogenesis; it delivers carcinogens directly to tissues, causes irritation and inflammation, and interferes with the body's natural protective barriers [39]. The dangers of tobacco are most commonly associated with cigarette smoking but also occur with cigars, pipes, smokeless tobacco, and exposure to environmental (secondhand) tobacco smoke. (See "Secondhand smoke exposure: Effects in adults".)

Tobacco cessation and prevention — Significant health benefits accompany quitting, even for longtime tobacco users. The health benefits of quitting can be seen at all ages and can be measured almost immediately after cessation [40]. Smoking cessation leads to reduced risk of most tobacco-related diseases and a decrease in all-cause mortality.

Tobacco cessation is associated with a reduction in cancer risk, and among smokers with a smoking-related cancer, smoking cessation decreases the risk of developing a second smoking-related malignancy and may improve the outcomes of cancer treatment [38,41]. (See "Benefits and consequences of smoking cessation", section on 'Benefits of smoking cessation'.)

The role of the health care provider in smoking cessation includes advice and counseling, referrals to behavioral therapy and support groups, and prescriptions for nicotine replacement and other medications [42,43]. (See "Pharmacotherapy for smoking cessation in adults" and "Behavioral approaches to smoking cessation" and "Overview of smoking cessation management in adults".)

Programs and policies that reduce youth initiation and facilitate smoking cessation should be implemented in both clinical and community settings to prevent initiation of tobacco use [44]. Many of these same efforts should also be extended to the prevention of youth initiation and use of e-cigarettes, which, along with other possible harms, may increase the risk of combustible tobacco use. (See "Prevention of smoking and vaping initiation in children and adolescents".)

PHYSICAL ACTIVITY — Decreased physical activity is associated with an increased risk for cancer [45-47], and it is estimated that a sedentary lifestyle is associated with 5 percent of cancer deaths [48]. However, the optimal duration, intensity, and frequency of physical activity that may afford cancer protection is unknown. Physical activity during certain periods of life, such as adolescence, may offer additional protection against disease, particularly for breast cancer [49,50].

Greater physical activity is associated with a decreased risk for many different types of cancers, [47,51-53], but the most compelling data are in the association with reduction in colon and breast cancer risk [47,51,54-59]. For example, In a meta-analysis of 52 studies, there was a 24 percent reduced risk of colon cancer when comparing the most versus the least active individuals (relative risk [RR] 0.76, 95% CI 0.72-0.81) [51]. In a subsequent meta-analysis including 21 studies, there were similar findings of decreased risk for both proximal and distal colon cancers [60]. In another meta-analysis, increased physical activity was associated with a 16 percent reduction in the risk of developing adenomatous colon polyps (RR 0.84, 95% CI 0.77-0.92) [61].

Several mechanisms have been proposed to explain the possible protective effect of physical activity, including reduction in circulating levels of insulin, hormones, and other growth factors; impact on prostaglandin levels; improved immune function, and altered bile acid metabolism [62-64].

Strategies to encourage physical activity — Strategies for clinicians to encourage physical exercise in their patients are presented elsewhere. (See "Exercise prescription and guidance for adults" and "Physical activity and exercise in older adults".)

OBESITY — Excess weight is associated with an increased risk of 13 types of cancer [65]. The relationship between obesity and cancer risk is discussed in detail separately, and associations between obesity and specific cancer types are discussed in the individual topics that cover the specific cancer type. (See "Overweight and obesity in adults: Health consequences", section on 'Cancer'.)

Weight loss — Weight loss methods including bariatric surgery have been associated with decreased cancer mortality. In one retrospective cohort study, bariatric surgery was associated with a 60 percent reduction in cancer mortality (5.5 versus 13.3 per 10,000 person-years) over seven-year follow-up [66]. In another retrospective cohort study, bariatric surgery was associated with a 33 percent reduction in overall cancer risk, with greater reductions of 40 to 55 percent in specific weight-related cancers: colon cancer, postmenopausal breast cancer, endometrial cancer, and pancreatic cancer [67]. The International Agency for Research on Cancer (IARC) analysis also found that bariatric surgery was associated with a reduced risk of endometrial and breast cancers [65].

Intentional, nonsurgical weight loss has also been associated with reduced cancer risk, though there are fewer studies, and these are complicated by difficulty controlling for intentional versus unintentional weight loss. In the Nurses’ Health Study, sustained weight loss of 22 pounds or more in women who had not used menopausal hormone therapy lowered breast cancer risk [68]. In two Women’s Health Initiative studies, compared with women who maintained stable weight during a mean follow-up of 11.4 years, women who had lost weight had a 29 percent lower risk of endometrial cancer (hazard ratio [HR] 0.71, 95% CI 0.54-0.95) and a 12 percent lower risk of postmenopausal breast cancer (HR 0.88, 95% CI 0.78‐0.98) [69,70].

Weight loss strategies are presented elsewhere. (See "Obesity in adults: Overview of management".)

ALCOHOL — Alcohol consumption increases the risk of multiple cancers, which is discussed in detail elsewhere. (See "Overview of the risks and benefits of alcohol consumption", section on 'Cancer'.)

Several mechanisms have been postulated to account for the carcinogenicity of alcohol [71]. Its solvent properties may allow carcinogens to penetrate cell membranes. Alcohol increases estrogen levels and impacts folate metabolism. Alcohol may also act as an irritant, causing increased cell production; as a transporter carrying carcinogens; as an inhibitor of DNA methylation; or as a prometabolite for identified carcinogens such as acetaldehyde [71-73].

Treatment of alcohol use disorder is discussed separately. (See "Alcohol use disorder: Treatment overview".)

ENVIRONMENTAL EXPOSURES — Potentially modifiable or avoidable environmental contributors to increased cancer incidence include exposure to excessive solar radiation or to artificial ultraviolet radiation; air pollution; radon gas in enclosed environments; and arsenic in drinking water.

●Sun and ultraviolet radiation exposure – Radiation from the sun is the primary cause of both melanomatous and nonmelanomatous skin cancer [74]. Ultraviolet radiation causes genetic mutations and interferes with the cutaneous immune system, limiting the body's ability to reject abnormal cells. Risk of squamous cell and basal cell cancer appear to correlate with total lifetime sun exposure [74]. Cumulative sun exposure may also increase melanoma risk, but repeated intense exposures leading to blistering burns, particularly in childhood and adolescence, may be even more dangerous [75].

Ultraviolet exposure from tanning beds has been classified as a human carcinogen, with a 75 percent increase in risk for melanoma in patients who utilized tanning booths before age 35 [76]. (See "Melanoma: Epidemiology and risk factors".)

●Air pollution – Diesel exhaust and particulate matter air pollution have been associated with increased risk of lung cancer. These are discussed elsewhere. (See "Cigarette smoking and other possible risk factors for lung cancer", section on 'Air pollution and diesel exhaust'.)

●Radon – The small increase in lung cancer risk associated with increased indoor radon levels is described separately. (See "Cigarette smoking and other possible risk factors for lung cancer", section on 'Radon'.)

●Arsenic – Long-term exposure to elevated arsenic levels in drinking water is associated with an increase in the risk of certain cancers, with strong evidence supporting a dose-response relationship for bladder cancer [77,78]. Most municipal water supplies are tested regularly for arsenic to ensure safe levels. Private drinking wells are more likely to have elevated levels and should be professionally tested regularly. (See "Arsenic exposure and chronic poisoning", section on 'Drinking water'.)

Recommendations for sun/ultraviolet protection — Individuals should generally limit the time spent in the sun, especially between the hours of 10 AM and 4 PM; wear hats, sunglasses, and other protective clothing; and use sunscreen with sun protection factor (SPF) 30 or higher. Because the majority of lifetime sun exposure usually occurs during childhood and adolescence, protective behaviors early in life will provide the greatest benefit. The Environmental Protection Agency (EPA) offers simple action steps for sun protection. In addition, the World Health Organization (WHO) has recommended that tanning bed use should be avoided entirely [79]. (See "Primary prevention of melanoma" and "Sunburn".)

DIET — Specific components of diet as well as overall dietary patterns have been studied in relation to the risk of cancer. Overall, dietary fat, fruits, and vegetables have not consistently been shown to affect cancer risk [80,81]. However, certain dietary patterns, as well as intake of other nutrients, particularly certain micronutrients, may offer a degree of protection against certain malignancies.

Specific dietary patterns may affect the incidence and mortality rate of certain types of cancer. These are discussed separately:

●(See "Epidemiology and risk factors for colorectal cancer", section on 'Diet' and "Cigarette smoking and other possible risk factors for lung cancer", section on 'Dietary factors' and "Risk factors for prostate cancer", section on 'Diet' and "Factors that modify breast cancer risk in women", section on 'Low-fat dietary pattern in postmenopausal women'.)

●(See "Epidemiology and risk factors for colorectal cancer", section on 'Red and processed meat'.)

●(See "Epidemiology and risk factors for colorectal cancer", section on 'Diet' and "Cigarette smoking and other possible risk factors for lung cancer", section on 'Dietary factors' and "Risk factors for prostate cancer", section on 'Diet' and "Factors that modify breast cancer risk in women", section on 'Low-fat dietary pattern in postmenopausal women'.)

●(See "Epidemiology and risk factors for colorectal cancer", section on 'Diet' and "Cigarette smoking and other possible risk factors for lung cancer", section on 'Dietary factors' and "Risk factors for prostate cancer", section on 'Diet' and "Factors that modify breast cancer risk in women", section on 'Low-fat dietary pattern in postmenopausal women'.)

●(See "Epidemiology and risk factors for colorectal cancer", section on 'Diet' and "Cigarette smoking and other possible risk factors for lung cancer", section on 'Dietary factors' and "Risk factors for prostate cancer", section on 'Diet' and "Factors that modify breast cancer risk in women", section on 'Low-fat dietary pattern in postmenopausal women'.)

Advice on dietary patterns — We agree with the 2020 American Cancer Society guideline on diet and physical activity for cancer prevention which recommends a healthy diet, defined as having a variety of vegetables (dark green, red and orange, fiber-rich legumes and others), fruits, and whole grains, and limiting or not including red and processed meats, sugar-sweetened beverages, or highly processed foods and refined grain products [82].

A meta-analysis of prospective studies of “healthy” and “unhealthy” dietary patterns found favorable associations between a healthy diet and lower risks of certain types of cancers [83]. In a large cohort study of the Mediterranean diet (ie, high intake of fruits, vegetables, nuts, legumes, whole wheat bread, fish, and olive oil), a two-point increase in dietary compliance (on a 10-point scale) was associated with a 4 to 12 percent lower risk of cancer [84,85]. In a study of cancer risk and mortality [86], all-cause mortality was 17 percent lower with a vegetarian diet than for non-vegetarians.

By contrast, studies of a "Western" diet have found an association with increased risk of some cancers compared with adherence to a "prudent" diet, although the components of a "Western" diet vary from study to study [87]. In another cohort study, diets high in ultra-processed foods were associated with greater than 10 percent increases in the risk of all-cancer and breast cancer [88]. Ultra-processed foods included mass-produced packaged breads, packaged snacks, sodas, reconstituted meat products with nitrite preservatives, instant soups, frozen meals, and others.

Further information on a healthy diet is presented elsewhere. (See "Healthy diet in adults".)

Diet components — While associations have been found between dietary patterns and cancer incidence, none of the following studies should be construed as supportive of dietary supplement use for cancer prevention. Certain of the following components may have toxicity (flavonoids may cause hepatic failure), and supplementation with certain compounds (eg, vitamin E) has been associated with increased cancer incidence.

Dietary fat — Dietary fat has been extensively studied as a possible factor explaining the variation in international cancer rates; however, data to support this theory are limited. This is discussed elsewhere. (See "Dietary fat", section on 'Cancer'.)

Intake of large amounts of alpha-linoleic acid and low amounts of linoleic acid may increase prostate cancer risk, which is discussed in detail elsewhere. (See "Risk factors for prostate cancer", section on 'Animal fat'.)

Red meat — Consumption of red and processed meat is associated with an increased risk of colorectal cancer and advanced prostate cancer [89-91]. The International Agency for Research on Cancer (IARC) classifies processed meat as a Group 1 human carcinogen [92]. (See "Epidemiology and risk factors for colorectal cancer", section on 'Other risk factors'.)

Fruits and vegetables — Evidence that greater intake of fruits and vegetables decreases cancer risk is inconsistent [93-96]. Data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a cohort study of nearly 500,000 European adults followed for nine years, found only a weak association between increased intake of fruits and vegetables and overall risk of cancer (hazard ratio [HR] 0.97, 95% CI 0.96-0.99) [81].

Some study findings for specific cancers include:

●Many epidemiologic studies [97,98], though not all [99], suggest a weak association between the intake of a diet high in fruits and vegetables and protection from colorectal cancer. A pooled analysis of 14 cohort studies (n >750,000), including the previous study [99], concluded that eating more than 800 g/day of fruit and vegetables, compared with less than 200 g/day, decreased risk for distal colon cancer (relative risk [RR] 0.74) but not for proximal cancer [100]. A subsequent meta-analysis of 19 cohort studies concluded a weaker protective effect, with most of the risk reduction attributable identified at a far lower threshold (100 g/day) of fruit and vegetable intake [101]. A meta-analysis of the relationship between fiber and colorectal cancer found no significant association between fruit, vegetable, or legume fiber and the incidence of colorectal cancer [102].

●Evidence is somewhat stronger, albeit still weak, for a possible protective link between prostate cancer and consumption of tomato products. Initial studies provided conflicting results, and a systematic review performed by the US Food and Drug Administration (FDA) found "very limited evidence" to support an association between tomato consumption and reduced risk of prostate or other (ovarian, gastric, and pancreatic) cancers [103]. An analysis of a prospective cohort of 51,529 men from the Health Professionals Follow-up Study has suggested that dietary intake of lycopene is associated with a lower incidence of prostate cancer and a decreased risk of lethal prostate cancer [104]. Analysis of tumor biomarkers was consistent with a possible role of inhibition of tumor neoangiogenesis as the mechanism underlying these observations. (See "Risk factors for prostate cancer", section on 'Lycopene and tomato based products'.)

●In an analysis of the Pooling Project of Prospective Studies of Diet and Cancer, total fruit and vegetable intake was inversely related to the incidence of estrogen-receptor (ER)-negative breast cancer, with vegetable intake alone associated with an 18 percent risk reduction comparing the highest quintile of intake with the lowest [105].

●A meta-analysis found that intake of high amounts of soy (20 mg/day of isoflavone) in Asian women was associated with a decreased risk for breast cancer compared with Asian women consuming lower amounts (5 mg/day) [106]. However, even the lowest intake of soy isoflavones in the Asian population was more than fivefold the "high" intake (0.8 mg/day) of women in Western countries, where studies have not shown a protective effect for soy. In another meta-analysis, Chinese women who were in the highest quintile of soy intake had a decreased risk of lung cancer compared with those in the lowest quintile [107]. Diets with increased intake of foods high in flavonoids, such as tomatoes, green peppers, berries, and citrus fruits have been associated with a modest decrease in breast cancer risk in Western populations [108].

Dairy — Several studies suggest that intake of low-fat dairy products may protect against breast cancer, mainly in premenopausal women [109-112]. In the largest prospective cohort study of over 88,000 women in the Nurses' Health Study, there was an inverse association between breast cancer risk and the intake of low-fat dairy products, calcium (mainly dairy intake), and vitamin D (mainly non-dairy intake) in premenopausal but not postmenopausal women [109]. By contrast, a large pooled analysis of eight prospective studies mainly comprising postmenopausal women did not find a strong association between dairy intake and breast cancer risk [113].

The relationship between dairy intake and ovarian cancer is uncertain, with most studies finding no association [114-117].

Fiber — Dietary fiber intake is associated with a reduction in colorectal cancer [118]. Though there has been some variance in results of individual observational studies, a World Cancer Research Fund Continuous Update Project dose response meta-analysis has found a decrease in risk of colorectal cancer with increasing intake of fiber. This analysis, including 15 studies with a total of 14,876 cases, showed a 9 percent lower risk of disease for every 10 g/day intake of foods containing fiber (RR 0.91, 95% CI 0.88-0.94). Similar inverse associations were found in North American (RR 0.92, 95% CI 0.88-0.96) and European (RR 0.90, 95% CI 0.85-0.96) populations [119]. (See "Epidemiology and risk factors for colorectal cancer", section on 'Fiber'.)

Glycemic load — Insulin and insulin-like growth factors promote cell proliferation, and it is hypothesized that hyperinsulinemia may promote certain cancers [120]. An increased risk for certain cancers has been associated with diabetes (primarily type 2) [121]. Patients with diabetes have a twofold or greater risk of cancers of the liver, pancreas, and endometrium and a slightly lower but increased risk for cancers of the colon, breast and bladder; the risk of prostate cancer is decreased in patients with diabetes [122]. However, studies of glycemic load and risk of breast or colon cancer show mixed results [123-136].

Omega-3 fatty acids and dietary fish — A systematic review of prospective studies evaluating the effect of omega-3 fatty acid consumption on tumor incidence concluded that there is no association between omega-3 fatty acids and cancer risk for 11 different types of cancer [137]. Ten studies evaluated in this review reported significant findings, but individual studies indicated both increased and decreased risk with no consistent pattern. A subsequent randomized trial found an increase in cancer risk for women treated with omega-3 fatty acids, but not for men [138].

Coffee and caffeine — Coffee intake has been associated with a lower risk of certain cancers, including endometrial and liver cancer [139,140]. World Cancer Research Fund Continuous Update Project dose response meta-analyses found a significant 7 percent lower risk of endometrial cancer (RR 0.93, 95% CI 0.91-0.96) and a 14 percent lower risk of liver cancer (RR 0.86, 95% CI 0.81-0.90) for every one cup of coffee/day. For endometrial cancer, the results were similar for decaffeinated coffee, a significant 8 percent lower risk (RR 0.92, 95% CI 0.87-0.97) per one cup/day. The effects of caffeine on several types of cancer are described separately. (See "Benefits and risks of caffeine and caffeinated beverages", section on 'Cancer'.)

VITAMINS AND MICRONUTRIENTS — Multiple observational and prospective studies and systematic reviews of the use of supplemental vitamins and minerals to prevent cancer have had negative results [141-145], although there are some positive studies [146,147]. However, supplements may be appropriate for some groups whose diets may be deficient for a variety of reasons. Any decision to take supplements should take place after an individual discussion with a health care provider.

The World Cancer Research Fund and American Institute for Cancer Research recommend against using supplements to prevent cancer [148]. People are encouraged to consume a healthy diet to meet nutritional needs. Further information on vitamin supplementation to prevent cancer is provided elsewhere. (See "Vitamin intake and disease prevention".)

Specific components

Vitamin D — Studies of the relationship between vitamin D intake or serum levels of 25(OH)D and cancer risk have been inconsistent [149]. Studies vary in regard to participants (sex, baseline serum levels), types of cancer evaluated, and dose of vitamin D. Overall, it does not appear that vitamin D supplements should be prescribed to decrease cancer risk [150]. (See "Vitamin D and extraskeletal health", section on 'Cancer'.)

Calcium — Increased calcium intake has been linked to reduced risk of colorectal cancer but may be associated with an increased risk of prostate cancer. There may be a minimum level of calcium intake, around 700 mg/day, that confers protection against colorectal cancer without significantly increasing prostate cancer risk.

●Colorectal cancer – Multiple observational studies have demonstrated that higher calcium intake (either dietary or supplemental) is associated with a reduced risk of colorectal cancer [151,152]. In a combined cohort from the Health Professionals Follow-up Study and Nurse's Health Study, the risk of distal, but not proximal, colon cancer was reduced in subjects who consumed more than 1250 mg/day elemental calcium versus ≤500 mg/day (relative risk [RR] 0.58, 95% CI 0.32-1.05) [153].

Calcium supplementation also appears to prevent the recurrence of colorectal adenomas. Meta-analyses have found a 12 to 13 percent lower risk of recurrence of adenomas in patients randomized to calcium supplementation [154,155]. (See "Overview of colon polyps".)

However, a protective effect of calcium supplementation was not shown by the Women's Health Initiative, which found no significant decrease in incidence or stage of colorectal cancer in the group assigned to receive calcium 500 mg and vitamin D 200 international units twice/day compared with placebo [156].

Overall, the World Cancer Research Fund Continuous Update Project panel concludes that “taking calcium supplements probably protects against colorectal cancer” [148].

●Prostate cancer – Case-control and prospective studies of calcium and prostate cancer have reported inconsistent results [157]. Three large cohort studies found an increased risk of prostate cancer with higher levels of calcium intake [158-160]. Two other prospective studies found no association [161,162]. (See "Risk factors for prostate cancer", section on 'Calcium and vitamin D'.)

Vitamin E — Evidence does not support a role for vitamin E supplementation in the prevention of cancer, and some evidence suggests that vitamin E supplementation may increase the risk of prostate cancer [163,164]. In 2014, the US Preventive Services Task Force (USPSTF) made a recommendation against use of vitamin E for cancer prevention, but also noted that vitamin E has few or no substantial harms [165]. (See "Vitamin intake and disease prevention", section on 'Cancer' and "Overview of vitamin E", section on 'Potential benefits'.)

Folic acid — The role of folic acid in cancer prevention is uncertain and is discussed in detail elsewhere. (See "Vitamin intake and disease prevention", section on 'Cancer'.)

Iron — Observational studies suggest that increased iron stores or dietary iron may be associated with increased risk for cancer [166,167]. A randomized trial conducted to evaluate the benefits of phlebotomy in patients with peripheral artery disease found a significant reduction in cancer incidence at six months (hazard ratio [HR] 0.65, 95% CI 0.43-0.97) in patients assigned to the phlebotomy group compared with controls [168]. This finding warrants confirmation with additional trial data.

Selenium — Although human epidemiologic studies and animal studies have suggested a potential protective effect of selenium on cancer incidence, randomized controlled human trials have not found a beneficial effect of selenium on overall cancer mortality or incidence [169-173].

Vitamin A and carotenoids — Trials evaluating vitamin A or carotenoid supplementation have reported no benefit or an increased risk of cancer. This is discussed in detail elsewhere. (See "Vitamin intake and disease prevention", section on 'Cancer' and "Cigarette smoking and other possible risk factors for lung cancer", section on 'Beta-carotene supplementation'.)

CHEMOPREVENTION — Chemoprevention for breast and prostate cancer are discussed in detail elsewhere:

●(See "Chemoprevention strategies in prostate cancer".)

●(See "Selective estrogen receptor modulators and aromatase inhibitors for breast cancer prevention".)

●(See "Cancer risks and management of BRCA1/2 carriers without cancer".)

Aspirin and other antiinflammatory drugs — Regular use of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) has been shown to decrease the risk of adenomatous polyps and colorectal cancer [174-177]. In high-risk patients with Lynch syndrome, a randomized controlled trial found 600 mg/day of aspirin decreased the risk of colorectal cancer by 60 percent [178]. The optimal dose of aspirin for patients at lower risk, however, has not been established [179]. (See "NSAIDs (including aspirin): Role in prevention of colorectal cancer".)

Several theories have been proposed for why aspirin and other NSAIDs are effective in reducing colorectal cancer risk and possibly effective for other cancers. These medications may cause cell cycle arrest or apoptosis (programmed cell death) of abnormal cells. Reduced risk may also relate to irreversible inhibition of cyclooxygenase 2 (COX-2). Inhibition of this enzyme decreases the synthesis of prostaglandins, which may inhibit tumor growth. Finally, aspirin may influence intracellular signaling through inhibition of phospholipase activity.

There are limited data to suggest that aspirin is associated with a reduction in cancers other than colorectal. Use of aspirin and other NSAIDS for cancer prevention is discussed elsewhere(See "Aspirin in the primary prevention of cardiovascular disease and cancer" and "Factors that modify breast cancer risk in women".)

Other medications — Although evidence is not compelling enough to suggest initiation of other drugs for cancer prevention, observational studies and limited experimental evidence suggest a possible future role for other drugs [180-191].

Metformin — Metformin has been associated with reduced incidence of several types of cancer in patients with type 2 diabetes.

●A systematic review and meta-analysis included 11 independent studies contributing 4042 cases of cancer and 529 deaths in patients with diabetes [183]. Both cancer incidence and cancer mortality were reduced by 30 percent among users of metformin. Reductions in the incidence of pancreatic and liver cancer as well as nonsignificant reductions for breast, colon, and prostate cancer were observed. There was a trend toward a dose-response relationship. In two subsequent meta-analyses in patients with diabetes, there was an association between metformin use and a decrease in colorectal cancer risk [184] and a decrease in risk of colorectal, liver, and lung cancers [185].

●In an observational study of 4085 patients in the United Kingdom who used metformin for type 2 diabetes from 1994 to 2003, cancer incidence was 40 percent lower than among diabetic patients who did not take metformin (7.3 versus 11.6 percent, hazard ratio [HR] 0.46, 95% CI 0.40-0.53) [181].

●In a prospective study of 1353 patients with type 2 diabetes in the Netherlands, during 9.6 years of follow-up, cancer mortality was reduced in those who used metformin (HR 0.43, CI 0.23-0.80) [182].

●In a registry-based case control study in the United Kingdom, metformin use was associated with a substantial decrease in pancreatic cancer risk among women but had no effect on cancer risk among men [186].

Among postulated mechanisms for such a benefit are the inhibition of cancer cell growth and suppression of HER2 overexpression and inhibition of mTOR [187-189]. Alternatively, these results may reflect increased risk due to use of other regimens for diabetes rather than decreased risk due to use of metformin.

Warfarin — Studies show mixed results regarding the association between warfarin use and cancer risk [191,192]. In a population-based cohort study of over one million people in Norway, warfarin users (for at least six months) had a lower incidence of all cancers diagnosed at least two years after initiating warfarin (incidence rate ratio [IRR] 0.84; 95% CI 0.82-0.86) [191]. Warfarin users also had lower incidence of lung, prostate, and breast cancer. Warfarin is known to block murine tumorigenesis, and it is postulated that its biochemical actions enhance antitumor immune surveillance [191].

Statins — Studies of statins show mixed results; there is no convincing evidence that statins influence the risk of cancer. An association between statin use and decreased risk of a variety of cancers (particularly gastrointestinal and breast cancers) has been suggested in multiple observational studies; however, such data are subject to confounding by risk factors and comorbidities [180]. By contrast, a meta-analysis of 27 randomized trials of statins (in which cancer prevention was not a primary outcome) did not find that statins reduced the incidence of any cancer [190].

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Beyond the Basics topics (see "Patient education: Medications for the prevention of breast cancer (Beyond the Basics)")

SUMMARY

●Many cancers are preventable. Basic lifestyle changes can have a tremendous impact on the rates of cancer. General lifestyle recommendations include avoiding tobacco, being physically active, maintaining a healthy weight, eating a healthy diet, limiting or eliminating alcohol, protecting against sexually transmitted infections, avoiding sun exposure, and obtaining appropriate cancer screening. (See 'Introduction' above.)

●Human papillomavirus (HPV), hepatitis C virus (HCV), human T-lymphotropic virus type 1 (HTLV-1), HIV, hepatitis B virus (HBV), Epstein-Barr virus (EBV), and Helicobacter pylori have been linked to human cancers. Exposure prevention, pre-exposure prophylaxis (PrEP), screening, vaccination, and early treatment can help prevent infection-associated cancers. (See 'Infections' above.)

●Tobacco use is the most preventable cause of cancer. Significant health benefits accompany quitting, even for longtime tobacco users. The health benefits of quitting can be seen at all ages and can be measured almost immediately after cessation. (See 'Tobacco use' above.)

●Decreased physical activity appears to increase the risk for cancer. Physical activity is associated with a decreased risk for many different types of cancers [47], but the most compelling data are in the reduction in colon and breast cancer risk. (See 'Physical activity' above.)

●Obesity has been found to increase the risk of many types of cancers, and weight loss decreases risk. (See 'Obesity' above.)

●Alcohol intake, even in light to moderate quantities, increases the risk for colon, breast, esophageal, and oropharyngeal cancer. (See 'Alcohol' above.)

●Potentially modifiable or avoidable environmental contributors to cancer incidence include exposure to excessive solar radiation or to artificial ultraviolet radiation, air pollution, radon gas in enclosed environments, and arsenic in drinking water. (See 'Environmental exposures' above.)

●Skin cancer is directly related to natural and artificial ultraviolet exposure. A history of blistering sunburns and indoor tanning, especially in youth and young adults, is of particular risk for melanoma; cumulative sun exposure has more impact on non-melanoma cancers. (See 'Environmental exposures' above.)

●The association of dietary fat, fruits, and vegetables with cancer risk is largely unconfirmed. Red meat and processed meat consumption may promote colorectal cancer and a high intake of tomatoes probably decreases prostate cancer risk. (See 'Diet' above.)

●High calcium intake (>2000 mg/day) increases risk for prostate cancer but is associated with a reduced risk of colorectal cancer. Folate in diet has been associated with a decreased risk of colon cancer, especially in women who drink alcohol; data on folic acid or multivitamin supplementation are inconsistent. (See 'Vitamins and micronutrients' above.)

●Chemoprevention may be helpful in high-risk patients, but risks and benefits should be weighed carefully. Aspirin and nonsteroidal antiinflammatory drugs (NSAIDs) offer protection against adenomatous polyps and colorectal cancer, and long-term use in low doses likely decreases cancer-related mortality risk from other solid tumors. (See 'Chemoprevention' above.)