In 2018, an estimated 1,735,350 people will be diagnosed with cancer in the United States, and an estimated 609,640 people will die of cancer.  Cancer incidence and mortality help to define the scope of the burden that cancer imposes on society, but these indicators do not fully characterize the impact that cancer has on cancer patients and their families. In addition to the physical morbidity caused by cancer, cancer is frequently associated with emotional distress and an overall reduction in quality of life.  Cancer has also been observed to be a financial stressor. In a population-based study in western Washington, 197,840 cancer patients were matched with an equal number of controls by age, sex, and zip code. Cancer patients were 2.6 times more likely to file for bankruptcy than the cancer-free controls (P < .05). 
Prevention is defined as the reduction of cancer mortality via reduction in the incidence of cancer. This can be accomplished by avoiding a carcinogen or altering its metabolism; pursuing lifestyle or dietary practices that modify cancer-causing factors or genetic predispositions; medical interventions (e.g., chemoprevention) or risk-reducing surgical procedures; or early detection strategies that can result in removal of precancerous lesions, such as colonoscopy for colorectal polyps.
The PDQ cancer prevention summaries are primarily organized by specific anatomic cancer site to facilitate consideration of the unique characteristics of specific malignancies. In this section, an overview of cancer prevention strategies is provided, including a summary of evidence for selected preventive strategies used in the prevention of a broad spectrum of malignancies. The strength of evidence and magnitude of effects of these strategies, however, may vary by cancer site. Other PDQ cancer prevention summaries address the prevention of specific types of cancer and provide more detailed descriptions of the evidence.
There are many common beliefs or speculations about causes of cancer. However, putative causes of cancer for which there exist very little scientific evidence, positive or negative, are not considered in these summaries. Therefore, absence of an environmental, dietary, or lifestyle factor from these summaries implies insufficient evidence for detailed consideration and not necessarily absence of effect. Many such factors are deserving of research regarding their potential roles in cancer, but if that research does not exist, has not been published, or the Editorial Board judges the research to be of insufficient quantity or of poor quality, they are not addressed in these summaries.
Carcinogenesis refers to an underlying etiologic pathway that leads to cancer. Several models of carcinogenesis have been proposed. Knudson proposed a “two-hit” model requiring a mutation in both copies of a gene resulting in cancer. Expansion of this concept has resulted in other widely cited models of carcinogenesis including those of Vogelstein and Kinzler  and Hanahan and Weinberg.  The model of Vogelstein and Kinzler emphasizes that cancer is ultimately a disease of damaged DNA, comprised of a series of genetic mutations that can transform normal cells to cancerous cells. The genetic mutations include inactivation of tumor suppressor genes and activation of oncogenes. Compared with cancers arising in the general population, individuals with a major inherited predisposition to cancer are born with inherited (i.e., germline) mutations in genes involved in cancer causation, giving them a head start on the pathway to cancer. Similar mutations would be expected to result in cancer progression among all individuals; however, in those without a major inherited cancer predisposition, the mutation would occur as a somatic mutation later during their lifetime.
The model of Hanahan and Weinberg focuses on the hallmark events at the cellular level that lead to a malignant tumor. In this model, the hallmarks of cancer include sustained angiogenesis, limitless replicative potential, evading apoptosis, self-sufficiency in growth signals, and insensitivity to antigrowth signals, leading to the defining characteristics of malignant tumors, which give them the ability to invade and metastasize. This model highlights the fact that malignant tumors arise and flourish within the environment of a whole organism. The tissue organizational field theory  posits that carcinogenesis is better conceptualized at the level of tissues rather than cells. This theory is based on the dual premise that carcinogenesis is driven by defects in tissue organization and that all cells are inherently in a proliferative state.
Models of carcinogenesis such as these are purposefully simplistic but, nevertheless, illustrate that carcinogenesis requires a constellation of steps that often take place for decades.
The complexity of carcinogenesis is magnified when one considers that the specific details of the carcinogenic pathway described by these models would be expected to have unique characteristics for each anatomic site. Under these circumstances, the risk factors and clinical characteristics of malignancies exhibit considerable variation by anatomic site and by different tumor types within the same anatomic site. For these reasons, human cancer is really not a single disease but is a family of different diseases.
The promise for cancer prevention is derived from observational epidemiologic studies that show associations between modifiable lifestyle factors or environmental exposures and specific cancers. The expectation is that, if a risk factor truly causes cancer, it would also be the case that a lifestyle modification (i.e., changing one's risk profile from bad to good) would actually reduce cancer risk, at least partially. This expectation can be fulfilled only if the association is due to a causal (and ideally, reversible) relationship. Because observational studies rarely provide conclusive evidence of such relationships, additional evidence is required.  For a few exposures, randomized controlled trials have tested whether interventions suggested by epidemiologic studies and leads based on laboratory research result in reduced cancer incidence and mortality.
Decades of research have consistently established the strong association between tobacco use and cancers of many sites. Specifically, cigarette smoking has been established as a cause of cancers of the lung, oral cavity, esophagus, bladder, kidney, pancreas, stomach, and cervix, and acute myelogenous leukemia. The body of epidemiologic evidence confirming these associations is substantial. Further support is demonstrated by the lung cancer death rates in the United States, which have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking followed by decreases in lung cancer death rates in men. As a single exposure that is relatively easy to measure accurately, this extensive body of evidence has led to the estimation that cigarette smoking causes 30% of all cancer deaths in the United States. Smoking avoidance and smoking cessation result in decreased incidence and mortality from cancer. (Refer to the PDQ summaries on Lung Cancer Prevention; Lung Cancer Screening; and Cigarette Smoking: Health Risks and How to Quit for more information.)
Globally, infectious agents have been estimated to cause 18% of all cancer cases.  The burden of cancers caused by infections is much greater in developing nations (26%) than in developed nations (8%). Infection with an oncogenic strain of human papillomavirus (HPV) is considered a necessary event for subsequent cervical cancer, and vaccine-conferred immunity results in a marked decrease in precancerous lesions. Oncogenic strains of HPV are also linked with cancers of the penis, vagina, anus, and oropharynx. Other examples of infectious agents that cause cancer are hepatitis B and hepatitis C viruses (liver cancer), Epstein-Barr virus (Burkitt lymphoma), and Helicobacter pylori (gastric cancer). If an infectious agent is truly a cause of cancer, then efficacious, anti-infective interventions would be expected in most instances to be effective cancer prevention interventions. This is the expectation with vaccines that protect against infection with oncogenic strains of HPV. (Refer to the PDQ summaries on Cervical Cancer Prevention; Cervical Cancer Screening; Liver (Hepatocellular) Cancer Prevention; and Liver (Hepatocellular) Cancer Screening for more information.)
Radiation is energy in the form of high-speed particles or electromagnetic waves. Exposure to radiation, primarily ultraviolet (UV) radiation and ionizing radiation, is a clearly established cause of cancer. Exposure to solar UV radiation is the major cause of nonmelanoma skin cancers, which are by far the most common malignancies in human populations. 
Ionizing radiation is radiation with enough energy to remove tightly bound electrons from their orbits, causing atoms to become charged or ionized. Ions formed in the molecules of living cells can go on to react with and potentially damage other atoms in the cell. At low doses (e.g., those associated with background radiation), the cells repair the damage rapidly. At moderate doses, the cells may be changed permanently or die from their inability to repair the damage. Cells changed permanently may go on to produce abnormal cells when they divide, and in some circumstances, these altered cells may become cancerous or lead to other abnormalities (e.g., birth defects). Defects in ability to repair damage caused by ionizing radiation may influence the impact of radiation exposure on cancer risk.
There is extensive epidemiologic and biologic evidence that links exposure to ionizing radiation with the development of cancer, and in particular, cancer that involves the hematological system, breast, lungs, and thyroid. The National Research Council of the National Academies, Committee to Assess the Health Risks from Exposure to Low Levels of Ionizing Radiation, the Biologic Effects of Ionizing Radiation VII report,  the most widely cited source on the topic, concluded after a comprehensive review of the medical literature that no dose of radiation should be considered completely safe, and attempts should be made to keep radiation doses as low as possible. In this report, three lines of evidence were cited documenting the association between ionizing radiation exposure and cancer. The first line of evidence comes from studies of the development of cancer among Japanese atomic-bomb survivors. Even at low doses of radiation, atomic-bomb survivors were at a significantly increased risk of developing cancer.  The second line of evidence comes from epidemiological studies of medically irradiated populations who were therapeutically irradiated for both malignant and benign diseases. Following high-dose radiation therapy for malignant disease, the risk of secondary malignancy is high. The relatively common use of radiation for benign disease between 1940 and 1960 resulted in a substantially increased relative risk (RR) of developing cancer. The third line of evidence comes from an increased risk of cancer-specific mortality associated with exposure to medical ionizing radiation, for both the recipients of diagnostic x-rays and x-ray personnel.
The major sources of population exposure to ionizing radiation are medical radiation (including x-rays, computed tomography [CT], fluoroscopy, and nuclear medicine) and naturally occurring radon gas in the basements of homes. Limiting unnecessary CT scans and other diagnostic studies, as well as reducing radiation exposure doses, are important prevention strategies.   (Refer to the PDQ summaries on Breast Cancer Prevention; Breast Cancer Screening; Skin Cancer Prevention; and Lung Cancer Prevention for more information.)
Exposure to ionizing radiation has increased during the last 2 decades as a result of the dramatic increase in the use of CT. Exposure to ionizing radiation associated with CT is in the range where carcinogenesis has been demonstrated.   Repeat exposure to radiation from medical imaging will further increase cancer risk, because risk is proportional to exposure. One study found that half the subjects who were exposed to radiation from medical imaging underwent repeat imaging within 3 years. Overall, 0.2% of the nearly 1 million participants followed for 3 years received doses above 50 mSv. 
One approach to estimate the potential contribution of exposure to ionizing radiation from medical imaging is to develop statistical models based on the estimated cancer risks associated with a range of dose levels. For example, one estimate of the CT scans performed in the United States in 2007 predicted that 29,000 (95% uncertainty limits of 15,000–45,000) cancers might result in the future. One-third of the projected cancers were caused by CT scans done on individuals aged 35 to 54 years. This estimate was derived from risk models based on organ-specific radiation doses from national surveys, frequency of CT scans in 2007 by age and sex from survey and insurance claim data, and the National Research Council’s "Biological Effects of Ionizing Radiation” report. 
Data are now emerging from studies large enough to directly estimate the cancer risk associated with CT scans. For example, in a cohort of 10.9 million Australians, electronic medical records were used to document the diagnostic CT scans of youths who received CT scans when they were aged 0 to 19 years. This cohort was then linked to the National Death Index and Australian Cancer Database.  Compared with those who did not have a CT scan, those who had at least one CT scan were statistically significantly more likely to be diagnosed with cancer as they were followed into young adulthood (RR, 1.24; 95% confidence interval [CI], 1.20–1.29; average follow-up in those who had a CT was 9.5 years). A statistically significant dose-response relationship was observed, with cancer risk increasing with each additional CT scan. Thus, the findings of cohort studies with directly measured CT scans now substantiate the statistical models and document the real-world cancer risks associated with exposure to ionizing radiation via medical imaging.
Medications that suppress the immune system in patients undergoing organ transplantation are associated with an increased cancer risk.  A retrospective population-based cohort study of solid-organ transplant recipients in Ontario, Canada during a 20-year period demonstrated that solid organ transplant recipients are at increased risk of cancer-specific death, regardless of age, sex, and organ transplanted. The risk is higher during the first 6 months posttransplant but persists for many years. It is especially high for cancers linked to viral infections. As outcomes of transplantation have improved, cancer mortality from secondary cancers has increased and is now the second most common cause of death after transplantation. 
Estimates concerning the potential contribution of diet to the population burden of cancer have varied widely. In contrast to the epidemiologic evidence on cigarette smoking and cancer, evidence for the influence of dietary factors and cancer is uncertain. An assessment of the potential role of diet entails measuring the net contribution of diets, comprising factors that may protect against cancer and other factors that may increase cancer risk. Measuring an individual’s usual diet and its direct relevance to cancer risk also poses challenges.
An assessment of the overall evidence of diet in relation to cancer prevention published by the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR)   was based on systematic reviews of the epidemiologic evidence. With respect to dietary factors that may protect against cancer, the greatest consistency was seen for fruits and nonstarchy vegetables. In the WCRF/AICR report, conclusions were reached that both fruits and nonstarchy vegetables were associated with “probable decreased risk” for cancers of the mouth, esophagus, and stomach. Fruits, but not nonstarchy vegetables, were also judged to be associated with “probable decreased risk” of lung cancer. Thus, even for the two classes of dietary exposure that the current evidence suggests may have the greatest cancer prevention potential, the evidence was judged to be less than convincing and was applicable to only a few malignancies.
Examples in which the type of study design led to substantively different results further illustrate the complexities of the relationship between food and nutrient intake and human cancer risk. Observational epidemiologic studies (case-control and cohort studies) have suggested associations between diet and cancer development, but randomized trials of interventions provided little or no support. For example, on the basis of population-based epidemiologic data, high-fiber diets were recommended to prevent colon neoplasms. However, a randomized, controlled trial of supplemental wheat bran fiber did not reduce the risk of subsequent adenomatous polyps in individuals with previously resected polyps. Ecologic, cohort, and case-control studies found an association between fat and red meat intake and colon cancer risk, but a randomized, controlled trial of a low-fat diet in postmenopausal women showed no reduction in colon cancer. The low-fat diet did not affect all-cancer mortality, overall mortality, or cardiovascular disease.
Life-long dietary patterns or dietary intake during specific life stages may be important in inducing or preventing cancer but would not be detected by relatively short-term, randomized, clinical trials.
With respect to dietary factors that may increase cancer risk, the strongest evidence in the WCRF/AICR report was for drinking alcohol. The evidence was judged to be “convincing” that drinking alcohol increased the risk of cancers of the mouth, esophagus, breast, and colorectum (the latter in men). Further, the evidence was judged to be “probable” that drinking alcohol increased the risk of liver cancer and colorectal cancer (CRC) (the latter in women).
In relation to human cancer, diets reflect the sum total of a complex mixture of exposures, as demonstrated by the examples of fruit/vegetable intake and alcohol consumption. No dietary factors appear to be uniformly relevant to all forms of cancer. (Refer to the PDQ summaries on Breast Cancer Prevention; Colorectal Cancer Prevention; and Lung Cancer Prevention for more information.)
A growing body of epidemiologic evidence suggests that people who are more physically active have a lower risk of certain malignancies than those who are more sedentary. In the WCRF/AICR report, the evidence was judged to be “convincing” that increased physical activity protects against CRC. The evidence was also judged to be “probable” that physical activity was associated with lower risk of postmenopausal breast cancer and endometrial cancer. As with the dietary factors described above, physical activity seems to play a more prominent role in selected malignancies. The inverse associations observed for selected malignancies make this a promising area for cancer prevention research, particularly since causal associations have not been established. The excess risk of many cancers seen with obesity, in combination with evidence to suggest that physical activity is inversely associated with at least a few cancers, raises the hypothesis that energy balance may influence cancer risk. (Refer to the PDQ summaries on Breast Cancer Prevention; Colorectal Cancer Prevention; and Endometrial Cancer Prevention for more information.)
Obesity is being increasingly recognized as an important cancer risk factor. The WCRF/AICR report concluded that obesity is convincingly linked to postmenopausal breast cancer and cancers of the esophagus, pancreas, colorectum, endometrium, and kidney. Furthermore, the WCRF/AICR report judged body fatness to be a probable risk factor for cancer of the gallbladder and the evidence to be “limited suggestive” for liver cancer. These conclusions from the WCRF/AICR evidence review were corroborated in a cohort study based on medical records data from 5.24 million adults in the United Kingdom.  The results of this U.K. cohort study also bolstered the evidence for an association between body mass index (BMI) and cancer of the gall bladder (RR, 1.3; 95% CI, 1.1–1.5 per 5 kg/m2 increase in BMI) and for liver cancer (RR, 1.19; 95% CI, 1.12–1.27 per 5 kg/m2 increase in BMI).  A prospective study of nationally representative cohorts that examined obesity in relation to cancer mortality emphasized that factors associated with cancer do not uniformly apply to all human malignancies. The study results revealed that obesity was associated with an increased risk of dying from obesity-associated malignancies, but obesity was not associated with overall cancer mortality.  If the associations between obesity and the cancers mentioned above are causal, which has yet to be established, the current increase in the prevalence of obesity in the United States and elsewhere poses a severe challenge to cancer prevention efforts. The magnitude of the impact of obesity on public health and the population burden of cancer is likely to be substantial, but is expected to be less than that of cigarette smoking. Smoking has a high prevalence and is causally associated with 13 types of cancer, and the magnitude of the associations are often much stronger than those observed for obesity. Furthermore, weight loss has yet to be shown to reduce risk of obesity-associated malignancies.  (Refer to the PDQ summaries on Breast Cancer Prevention; Colorectal Cancer Prevention; Endometrial Cancer Prevention; and Lung Cancer Prevention for more information.)
A recent analysis  of the long-running Nurses' Health Study and Health Professionals Follow-up Study estimated the proportions of cancer cases and deaths in the U.S. population on the basis of adoption of a low-risk lifestyle (characterized by being a never-smoker or former smoker, having no or moderate alcohol drinking, having a BMI between 18.5 and 27.5, and meeting the 2008 Physical Activity Guidelines for Americans). One major weakness of the study was that its premise assumed the causality of the nonsmoking risk factors. The analysis was further weakened by using self-reported measures of diet and alcohol use, and by measuring only leisure-time (rather than all) physical activity. Also, the authors did not present the effects of the nonsmoking risk factors after accounting for smoking. This analysis and others with similar weaknesses should therefore be interpreted cautiously.
Observational studies suggest that all-cancer incidence and mortality are slightly increased (10%–15%) in individuals with diabetes, although the increase is greater for certain organ sites and null for others.    Given that there is biologic heterogeneity in diabetes and cancer, that diabetes and cancer share a number of risk factors, and that diabetes almost always requires long-term medication use, it is not possible to say what the observed associations (especially those that are small) actually represent. Furthermore, most observational studies rely on self-reports of diabetes (as “has diabetes” or “does not have diabetes”), making it impossible to explore whether associations differ by diabetic type or severity, degree of diabetic control, and other factors that can be determined only through the use of biospecimens and repeated measures. These limitations must be kept in mind when findings are interpreted.
At least four of the following characteristics of diabetes have been hypothesized to increase cancer risk:
Diabetes and cancer share a number of risk factors, including aging, obesity, smoking, unhealthy diet, and physical inactivity.  Diabetic treatments include exogenous insulin injections as well as oral medications that modify insulin secretion and sensitivity, reduce blood glucose levels, or prevent the kidneys from reabsorbing blood glucose. 
In prospective observational studies, risk of and death due to liver, pancreas, colon/colorectum, and female breast cancer are consistently higher in persons with diabetes. Increases in risk or death also have been observed for cancer of the endometrium, ovary, bladder, and oral cavity/pharynx. In a prospective cohort with long-term follow-up of more than a million U.S. adults  —with analyses that controlled for age, education, BMI, smoking, alcohol intake, vegetable intake, red meat intake, physical activity, and aspirin use—the greatest increase in mortality for the aforementioned cancer sites was for liver cancer in males (RR, 2.26; 95% CI, 1.89–2.70); the lowest was for breast cancer in females (RR, 1.16; 95% CI, 1.03–1.29). With the exception of death due to male breast cancer (analysis included 12 patients with diabetes who were dying of the cancer), the remainder of positive statistically significant RRs were no greater than 1.5. A pooled data analysis of 97 prospective studies (almost 821,000 individuals) that controlled for age, smoking status, and BMI and presented non–sex-stratified hazard ratios (HRs)  reported findings similar to those in the aforementioned study; however, contrary to that study, increases in risk of death caused by lung (HR, 1.27; 95% CI, 1.13–1.43) and ovarian cancer (HR, 1.45; 95% CI, 1.03–2.02) were found. An umbrella review of meta-analyses  of type 2 diabetes and cancer reported a statistically significant 10% increase in risk of all-cancer incidence, a statistically significant 16% increase in all-cancer mortality, and statistically significant increases in the incidence of 12 cancers. Relative increases in the incidence of pancreas, endometrium, and liver cancer were roughly twofold and statistically significant.
Metformin has been associated with a decrease in breast cancer incidence and mortality in observational studies and is currently under study in clinical trials. Metformin has been hypothesized to reduce risk by inhibiting tumor cell growth and proliferation through adenosine monophosphate (AMP)–kinase activation. The use of medications that affect incretin receptor signaling has been postulated to increase pancreatic cancer incidence, but neither animal nor clinical data (which are limited) support that claim at this time.  Long-term use of exogenous, long-acting insulin has never consistently been shown to increase cancer risk.
Many of the groundbreaking observational studies in cancer etiology date back to a time when widespread cancer screening did not occur. Given the extensive uptake of screening for certain cancers over the past quarter-century, recently conducted observational etiologic studies included participants whose disease was detected through screening. When overdiagnosis exists with screening, and screening behavior or willingness to seek diagnostic evaluation is correlated with cancer risk factors, relative risk measures generated from today’s etiology studies may not agree with those from studies conducted before the widespread use of screening. This is because overdiagnosed cases would never have been diagnosed in the absence of screening. For example, assume that blue eyes (relative to brown eyes) are associated with receiving prostate-specific antigen (PSA) screening or preference for diagnostic biopsy, but not with prostate cancer. In the absence of screening, a null result would have been observed for the association of blue eyes and prostate cancer. In the presence of screening, blue eyes would be associated with prostate cancer, because blue eyes would lead to screening, and screening would detect overdiagnosed cases. 
Chemoprevention refers to the use of natural or synthetic compounds to interfere with early stages of carcinogenesis, before invasive cancer appears.  Several agents have proven benefit.
Selective estrogen receptor modulators (tamoxifen and raloxifene), taken daily for up to 5 years, reduce breast cancer incidence by 50% in high-risk women.  Widespread use of these medications for prevention is limited because of side effects (hot flashes, and in the case of tamoxifen, endometrial cancer). (Refer to the PDQ summary on Breast Cancer Prevention for more information.)
Finasteride (an alpha-reductase inhibitor) lowers the incidence of prostate cancer.  Finasteride lowers PSA levels, resulting in fewer prostate biopsies, and shrinks normal prostate tissue, which allows easier detection of cancers. Both of these effects may account for the finding that finasteride recipients have an absolute higher incidence of high-grade prostate cancer, i.e., a lower incidence of low-risk cancer (lower overdiagnosis). (Refer to the PDQ summary on Prostate Cancer Prevention for more information.)
COX-2 inhibitors inhibit the cyclooxygenase enzymes that are involved in the synthesis of proinflammatory prostaglandins. Evidence suggests that COX-2 inhibitors may prevent colon and breast cancer but concerns about cardiovascular risk preclude extensive study. A randomized controlled trial (RCT) of moderately high-dose celecoxib in patients with arthritis showed no difference in cardiovascular outcomes when compared with nonselective nonsteroidal anti-inflammatory agents (NSAIDs).  (Refer to the PDQ summaries on Breast Cancer Prevention and Colorectal Cancer Prevention for more information.)
Aspirin has been studied extensively as a chemopreventive agent. A secondary analysis of pooled data from seven placebo-controlled RCTs with primary endpoints of vascular events showed that daily aspirin for at least 4 years reduced overall cancer deaths by 18% (odds ratio, 0.82; 95% CI, 0.70–0.95).  The effect of aspirin on cancer incidence seems to be limited to colorectal cancer. A significant side effect of aspirin is bleeding, which may preclude widespread use for cancer prevention. Because aspirin may help reduce death from cardiovascular disease (which is responsible for more deaths than cancer), use of aspirin should be considered in a larger context of prevention beyond cancer. Similarly, serious harms from bleeding (from gastrointestinal tract or intracranial) should be considered in light of patients' individual risks of specific harms. (Refer to the PDQ summary on Colorectal Cancer Prevention for more information.)
Some have advocated vitamin and mineral supplements for cancer prevention. Many different mechanistic pathways for anticancer effects have been invoked. A commonly tested hypothesis is that antioxidant vitamins may protect against cancer, based on the premise that oxidative damage to DNA leads to cancer progression. Hence preventing oxidative DNA damage would prevent progression to cancer. However, the evidence is insufficient to support the use of multivitamin and mineral supplements or single vitamins or minerals to prevent cancer.  Beta carotene is an antioxidant that was thought to prevent or reverse smoking-related changes leading to lung cancer based on the results of several observational epidemiologic studies examining either dietary intake of beta carotene from food sources or blood levels as a marker of dietary intake.  However, two prospective, placebo-controlled trials found that smokers and former smokers who received beta carotene supplements had increased lung cancer incidence and mortality. 
Other unanticipated adverse events have been documented for dietary supplement use. A meta-analysis of 11 randomized, double-blind, placebo-controlled trials of daily doses of calcium greater than or equal to 500 mg/day versus placebo documented that calcium supplements were associated with a significantly elevated risk of myocardial infarction (RR, 1.27; 95% CI, 1.01–1.59).  Dietary calcium intake has not been observed to be associated with an increased risk of myocardial infarction.  The discrepancy in findings between calcium in the diet versus high-dose supplementation raises questions about the value of dietary supplements compared with dietary intake. The Iowa Women’s Health Study, an observational study that enrolled over 40,000 women aged 55 to 69 years in 1986, examined the association between dietary supplement use and mortality.  Statistically significant excess mortality risk was observed with the use of multivitamins, B6, folic acid, iron, magnesium, zinc, and copper. Only calcium users were associated with a statistically significant reduction in mortality rates compared with nonusers.
Research into the potential anticancer properties of vitamin and mineral supplements is ongoing, and the results continue to reinforce the lack of efficacy of vitamin supplements in preventing cancer. The extended follow-up results of the Selenium and Vitamin E Cancer Prevention Trial (SELECT) found a statistically significant excess risk of prostate cancer associated with vitamin E supplementation (400 IU/day of all rac-α-tocopherol acetate) compared with placebo (HR, 1.17; 99% CI, 1.0004–1.36; P = .008). The absolute increase in risk of prostate cancer with vitamin E use was 1.6 per 1000 person-years. Selenium did not reduce the risk of prostate cancer (HR, 1.09; 99% CI, 0.93–1.27). 
The results of the Physicians’ Health Study II demonstrated that supplementation with vitamin E and/or vitamin C had no benefit compared with placebo in preventing either prostate cancer incidence or total cancer incidence. 
The results of the Women’s Antioxidant Cardiovascular Study indicated that, compared with placebo, supplementation with vitamin C, vitamin E, or beta carotene was not efficacious in reducing total cancer incidence.  In this same study, daily supplements containing folic acid, vitamin B6, and vitamin B12 were compared with placebo; this intervention was not efficacious in reducing the overall risk of developing cancer.  An exploratory analysis of pooled data from two Norwegian randomized controlled trials showed an increase in both cancer incidence and cancer death in patients treated with folic acid and vitamin B12 versus those receiving placebo or vitamin B6 alone.  (Refer to the PDQ summaries on Breast Cancer Prevention; Colorectal Cancer Prevention; Lung Cancer Prevention; and Prostate Cancer Prevention for more information.)
Vitamin D has also generated interest as a potential anti-cancer agent. Sources of vitamin D include cutaneous synthesis upon exposure to sunlight, dietary intake, and supplements. Evidence for the efficacy of vitamin D supplements with or without calcium in preventing cancer incidence is available as a secondary endpoint from randomized controlled trials, with a summary of the results from three trials providing evidence of lack of efficacy.  A fourth randomized, controlled trial further corroborates this lack of cancer chemopreventive effect.  Presently, the overall body of experimental evidence in humans indicates that at the doses studied (range: 400–1,100 IU daily), vitamin D supplements do not reduce or increase the overall risk of cancer.  This is a topic of ongoing interest, and a large-scale randomized trial of vitamin D (2,000 IU/day) and marine omega-3 fatty acid is under way that includes cancer as a primary endpoint. 
None of the randomized controlled trials mentioned above studied multivitamin supplements as commonly taken by the general U.S. population; however, a separate arm of the Physician Health Study (PHS) II directly studied this question. In the PHS II, 14,641 male physicians were randomly assigned to receive either a daily multivitamin supplement or a placebo for a median of 11 years.  Multivitamin supplements were associated with an 8% relative decrease in cancer incidence (HR, 0.92; 95% CI, 0.86–0.998; P = .04). The overall reduction in cancer risk was more pronounced in men who had been diagnosed with cancer before the study began (HR, 0.66; 95% CI, 0.50–0.88) than in those with no history of cancer (HR, 0.95; 95% CI, 0.87–1.03), suggesting that the small benefit of multivitamins in reducing overall cancer incidence largely stemmed from the prevention of second primary cancers. This puzzling result, along with the weak association and multiple statistical comparisons made for many different trial endpoints, diminishes the strength of evidence provided by the PHS II trial. Of note, no significant association between multivitamin use and total mortality was observed in the PHS II (HR, 0.94; 95% CI, 0.88–1.02; P = .13), suggesting neither a negative nor positive effect on life span.  This finding differs from the association between supplements and higher mortality reported in the observational Iowa Women’s Health Study. 
The relationship between environmental pollutants and cancer risk has been of long-standing interest to researchers and the public. When estimates of the potential burden of cancer have been calculated for different classes of exposure, the factors described earlier, such as cigarette smoking and infections, have represented much greater proportions of the cancer burden than have environmental pollutants. Nevertheless, some associations between environmental pollutants and cancer have been clearly established. Perhaps because the lung is most heavily exposed to air pollutants, many of the most firmly established examples of pollutants and cancer relate specifically to lung cancer, including secondhand tobacco smoke, indoor radon, outdoor air pollution, and asbestos for mesothelioma. Another environmental pollutant linked with cancer is highly concentrated inorganic arsenic in drinking water, which is causally associated with cancers of the skin, bladder, and lung. Many other environmental pollutants, such as pesticides, have been assessed for risk with human cancer, but with indeterminate results. There are challenging methodological issues to address in these studies, such as accurately measuring exposures for long periods, which often make it difficult to clearly establish an association between an environmental pollutant and cancer.
The list of topics considered above is not exhaustive. Other lifestyle and environmental factors known to affect cancer risk (either beneficially or detrimentally) include certain sexual and reproductive practices, the use of exogenous estrogens, and certain occupational and chemical exposures.
In this summary, factors were selected that appear to impact the risk of several types of cancer and that have been identified as being potentially modifiable. These include cigarette smoking, which has been conclusively linked with a wide range of malignancies; avoidance of cigarette smoking has been shown to reduce cancer incidence. Other potential modifiable cancer risk factors include alcohol consumption and obesity; physical activity is inversely associated with the risk of certain cancers. More research is needed to determine whether these associations are causal and whether avoiding risk behaviors or increasing protective behaviors would actually reduce cancer incidence.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Added text to state that the expectation is that, if a risk factor truly causes cancer, it would also be the case that a lifestyle modification (i.e., changing one's risk profile from bad to good) would actually reduce cancer risk, at least partially; this expectation can be fulfilled only if the association is due to a causal (and ideally, reversible) relationship. Because observational studies rarely provide conclusive evidence of such relationships, additional evidence is required (cited Song et al. as reference 4).
Added text to state that the risk of cancer-specific death after a solid organ transplant is higher during the first 6 months posttransplant but persists for many years; it is especially high for cancers linked to viral infections.
Added text to state that a recent analysis of the long-running Nurses' Health Study and Health Professionals Follow-up Study estimated the proportions of cancer cases and deaths in the U.S. population on the basis of adoption of a low-risk lifestyle (characterized by being a never-smoker or former smoker, having no or moderate alcohol drinking, having a BMI between 18.5 and 27.5, and meeting the 2008 Physical Activity Guidelines for Americans). Also added text to state that one major weakness of the study was that its premise assumed the causality of the nonsmoking risk factors; the analysis was further weakened by using self-reported measures of diet and alcohol use, and by measuring only leisure-time physical activity. Also, the authors did not present the effects of the nonsmoking risk factors after accounting for smoking; this analysis and others with similar weaknesses should therefore be interpreted cautiously (cited Song et al. as reference 4).
This summary is written and maintained by the PDQ Screening and Prevention Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about cancer prevention. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
This summary is reviewed regularly and updated as necessary by the PDQ Screening and Prevention Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
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The preferred citation for this PDQ summary is:
PDQ® Screening and Prevention Editorial Board. PDQ Cancer Prevention Overview. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/causes-prevention/hp-prevention-overview-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389451]
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