Cancer prevention

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Cancer prevention is the practice of taking active measures to decrease the incidence of cancer and mortality.[1][2] The practice of prevention is dependent upon both individual efforts to improve lifestyle and seek preventative screening and socioeconomic or public policy related to cancer prevention.[3] Globalized cancer prevention is regarded as a critical objective due to its applicability to large populations, reducing long term effects of cancer by promoting proactive health practices and behaviors, and its perceived cost-effectiveness and viability for all socioeconomic classes.[2]

The majority of cancer cases are due to environmental risk factors, and many, but not all, of these environmental factors are controllable lifestyle choices.[4] Greater than a reported 75% of cancer deaths could be prevented by avoiding risk factors including: tobacco, overweight / obesity, an insufficient diet, physical inactivity, alcohol, sexually transmitted infections, and air pollution.[5][6] Not all environmental causes are controllable, such as naturally occurring background radiation, and other cases of cancer are caused through hereditary genetic disorders. Current gene editing techniques under development may serve as preventative measures in the future.[7] Future preventative screening measures can be additionally improved by minimizing invasiveness and increasing specificity by taking individual biologic make up into account, also known as "population-based personalized cancer screening."[2]

The concerned[edit]

Death rate adjusted for age for malignant cancer per 100,000 inhabitants in 2004.[8]

Anyone can get cancer,[9] the age is one of the biggest factors that can make a person more likely to get cancer: 3 out of 4 cancers are found in people aged 55 or older.

Dietary[edit]

This advertisement advises a healthy diet to prevent cancer.

While many dietary recommendations have been proposed to reduce the risk of cancer, the evidence to support them is not definitive.[10][11] The primary dietary factors that increase risk are obesity and alcohol consumption; with a diet low in fruits and vegetables and high in red meat being implicated but not confirmed.[12][13] A 2014 meta-analysis did not find a relationship between fruits and vegetables and cancer.[14] Consumption of coffee is associated with a reduced risk of liver cancer.[15] Studies have linked excessive consumption of red or processed meat to an increased risk of breast cancer, colon cancer, and pancreatic cancer, a phenomenon which could be due to the presence of carcinogens in meats cooked at high temperatures.[16][17] Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains, and fish, and an avoidance of processed and red meat (beef, pork, lamb), animal fats, and refined carbohydrates.[10][11]

Physical activity[edit]

Research shows that regular physical activity helps to reduce up to 30%[18][19] the risk of a variety of cancer types, such as colon cancer, breast cancer, lung cancer and endometrium cancer.[20][21] The biological mechanisms underlying this association are still not well understood[21] but different biological pathways involved in cancer have been studied suggesting that physical activity reduces cancer risk by helping weight control, reducing hormones such as estrogen and insulin, reducing inflammation and strengthening the immune system.[21][22]

Medication[edit]

The concept that medications can be used to prevent cancer is attractive, and evidence supports their use in a few defined circumstances.[23] In the general population, NSAIDs reduce the risk of colorectal cancer however due to the cardiovascular and gastrointestinal side effects they cause overall harm when used for prevention.[24] Aspirin has been found to reduce the risk of death from cancer by about 7%.[25] COX-2 inhibitor may decrease the rate of polyp formation in people with familial adenomatous polyposis however are associated with the same adverse effects as NSAIDs.[26] Daily use of tamoxifen or raloxifene has been demonstrated to reduce the risk of developing breast cancer in high-risk women.[27] The benefit verses harm for 5-alpha-reductase inhibitor such as finasteride is not clear.[28]

Vitamins have not been found to be effective at preventing cancer,[29] although low blood levels of vitamin D are correlated with increased cancer risk.[30][31] Whether this relationship is causal and vitamin D supplementation is protective is not determined.[32] Beta-Carotene supplementation has been found to increase lung cancer rates in those who are high risk.[33] Folic acid supplementation has not been found effective in preventing colon cancer and may increase colon polyps.[34] It is unclear if selenium supplementation has an effect.[35]

Vaccination[edit]

Anti-cancer vaccines can be preventative / prophylactic or be used as therapeutic treatment.[2] All such vaccines incite adaptive immunity by enhancing cytotoxic T lymphocyte (CTL) recognition and activity against tumor-associated or tumor-specific antigens (TAA and TSAs).

Vaccines have been developed that prevent infection by some carcinogenic viruses.[36] Human papillomavirus vaccine (Gardasil and Cervarix) decreases the risk of developing cervical cancer.[36] The hepatitis B vaccine prevents infection with hepatitis B virus and thus decreases the risk of liver cancer.[36] The administration of human papillomavirus and hepatitis B vaccinations is recommended when resources allow.[37]

Some cancer vaccines are usually immunoglobulin-based and target antigens specific to cancer or abnormal human cells.[2][38] These vaccines may be given to treat cancer during the progression of disease to boost the immune system's ability to recognize and attack cancer antigens as foreign entities. Antibodies for cancer cell vaccines may be taken from the patient's own body (autologous vaccine) or from another patient (allogeneic vaccine).[36] Several autologous vaccines, such as Oncophage for kidney cancer and Vitespen for a variety of cancers, have either been released or are undergoing clinical trial. FDA-approved vaccines, such as Sipuleucel-T for metastasizing prostate cancer or Nivolumab for melanoma and lung cancer can act either by targeting over-expressed or mutated proteins or by temporarily inhibiting immune checkpoints to boost immune activity.[2][39]

Screening[edit]

Screening procedures, commonly sought for more prevalent cancers, such as colon, breast, and cervical, have greatly improved in the past few decades from advances in biomarker identification and detection.[2]

Cervical Cancer[edit]

Cervical cancer is usually screened through in vitro examination of the cells of the cervix (e.g. Pap smear), colposcopy, or direct inspection of the reproductive system, or DNA-testing for HPV, considered an oncogenic virus.[40] Recommended screening age is between 20 - 30 years, and women who are between 21 - 29 years old are encouraged to receive Pap smear screens every three years, and those over 29 every five years. [2] For women older than the age of 65 and with no history of cervical cancer or abnormality, and with an appropriate precedence of negative Pap test results may cease regular screening.[41]

Still, adherence to recommended screening plans depends on age and may be linked to "educational level, culture, psychosocial issues, and marital status," further emphasizing the importance of addressing these challenges in regards to cancer screening.[2]

Colorectal Cancer[edit]

Colorectal cancer is most often screened with the fecal occult blood test (FOBT). Variants of this test include guaiac-based FOBT (gFOBT), the fecal immunochemical test (FIT), and stool DNA (sDNA) testing.[42] Further testing includes flexible sigmoidoscopy (FS), total colonoscopy (TC), or computed tomography (CT) scans if a TC is non-ideal. A recommended age at which to begin screening is 50 years. However, this is highly dependent on medical history and exposure to CRC risk factors. Effective screening has been shown to reduce CRC incidence by 33% and CRC morality by 43%. [2]

Breast Cancer[edit]

The estimated number of new breast cancer cases in the US in 2018 is predicted to be more than 1.7 million, with more than six-hundred thousand deaths.[43] Factors such as breast size, reduced physical activity, obesity and overweight status, infertility and never having had children, hormone replacement therapy (HRT), and genetics are risk factors for breast cancer.[2] Mammograms are widely used to screen for breast cancer, and are recommended for women 50-74 years of age by the US Preventive Services Task Force (USPSTF). However, the USPSTF recommended against mammographies for women 40-49 years old due to possibility of overdiagnosis.[2][44]

Preventable causes of cancer[edit]

As of 2017, tobacco use, diet and nutrition, physical activity, obesity/overweight status, infectious agents, and chemical and physical carcinogens have been reported to be the leading areas where cancer prevention can be practiced through enacting positive lifestyle changes, getting appropriate regular screening, and getting vaccinated.[45]

The development of many common cancers are incited by such risk factors. For example, consumption of tobacco and alcohol, a medical history of genital warts and STDs, immunosuppression, unprotected sex, and early age of first sexual intercourse and pregnancy all may serve as risk factors for cervical cancer. Obesity, red meat of processed meat consumption, tobacco and alcohol, and a medical history of inflammatory bowel diseases are all risk factors for colorectal cancer (CRC). On the other hand, exercise and consumption of vegetables may help decrease the risk of CRC.[2]

Several preventable causes of cancer were highlighted in Doll and Peto's landmark 1981 study[46], estimating that 75 – 80% of cancers in the United States could be prevented by avoidance of 11 different factors. A 2013 review of more recent cancer prevention literature by Schottenfeld et al.,[47] summarizing studies reported between 2000 and 2010, points to most of the same avoidable factors identified by Doll and Peto. However, Schottenfeld et al. considered fewer factors (e.g. non inclusion of diet) in their review than Doll and Peto, and indicated that avoidance of these fewer factors would result in prevention of 60% of cancer deaths. The table below indicates the proportions of cancer deaths attributed to different factors, summarizing the observations of Doll and Peto, Shottenfeld et al. and several other authors, and shows the influence of major lifestyle factors on the prevention of cancer, such as tobacco, an unhealthy diet, obesity and infections.[48]

Proportions of cancer deaths in the United States attributed to different factors
Factor Doll and Peto[49] Schottenfeld et al.[50] Other reports
Tobacco 30% 30% 38% men, 23% women,[51] 30%,[52] 25-30%[53]
Deleterious diet 35% - 32%,[54] 10%,[55] 30-35%[53]
Obesity * 10% 14% women, 20% men, among non-smokers,[56] 10-20%,[53] 21% U.S., 9% China[57]
Infection 10% 5-8% 7-10%,[58] 8% developed nations, 26% developing nations,[52] 10% high income, 25% African[53]
Alcohol 3% 3-4% 3.6%,[52] 8% USA, 20% France[59]
Occupational exposures 4% 3-5% 2-10%, may be 15-20% in men[60]
Radiation (solar and ionizing) 3% 3-4% up to 10%[53]
Physical inactivity * <5% 7%[61]
Reproductive and sexual behavior 1-13% - -
Pollution 2% - -
Medicines and medical procedures 1% - -
Industrial products <1% - -
Food additives <1% - -

*Included in diet

†Carcinogenic infections include: for the uterine cervix (human papillomavirus [HPV]), liver (hepatitis B virus [HBV] and hepatitis C virus [HCV]), stomach (Helicobacter pylori [H pylori]), lymphoid tissues (Epstein-Barr virus [EBV]), nasopharynx (EBV), urinary bladder (Schistosoma hematobium), and biliary tract (Opisthorchis viverrini, Clonorchis sinensis)

History of Cancer Prevention[edit]

Cancer has been thought to be a preventable disease since the time of Roman physician Galen, who observed that unhealthy diet was correlated with cancer incidence. In 1713, Italian physician Ramazzini hypothesized that abstinence caused lower rates of cervical cancer in nuns. Further observation in the 18th century led to the discovery that certain chemicals, such as tobacco, soot and tar (leading to scrotal cancer in chimney sweepers, as reported by Percivall Pot in 1775), could serve as carcinogens for humans. Although Potts suggested preventative measures for chimney sweeps (wearing clothes to prevent contact bodily contact with soot), his suggestions were only put into practice in Holland, resulting in decreasing rates of scrotal cancer in chimney sweeps. Later, the 19th century brought on the onset of the classification of chemical carcinogens.[62]

In the early 20th century, physical and biological carcinogens, such as X ray radiation or the Rous Sarcoma Virus discovered 1911, were identified. Despite observed correlation of environmental or chemical factors with cancer development, there was a deficit of formal prevention research and lifestyle changes for cancer prevention were not feasible during this time.[62]

Timeline of Cancer Prevention Research [63][edit]

In the 1970s, federally-funded efforts brought the importance of diet and early screening in the prevention of cancer to the public eye.

1971 - Nixon signs NCA, federally-funded cancer research established.

1974 - Disadvantaged women benefit from NCI-funded ovarian screening.

1977 - Senate Select Committee on Nutrition publishes dietary guidelines for cancer prevention.

1978 - Community Hospital Oncology Program (CHOP)

1979 - NCI diet for cancer prevention: low-fat, low alcohol, increased fiber, balanced diet.

In the 1980s, early federally-funded programs and institutions were established to pioneer research in the field of cancer prevention.

1981 - Community Clinical Oncology Program.

1982 - "Chemoprevention:" Nutrients and compounds for cancer prevention. SBIR moves research to private sector. Smoking, Tobacco, and Cancer Program.

1983 - NCI begins chemoprevention and early detection research. Clinical Oncology Program (CCOP) and Division of Cancer Prevention and Control (DCPC) added to NCI.

1984 - DCPC research and clinical trials, meets with Kellogg company to discuss health claims in cereal publicity

1985 - Linxian China Dysplasia trial and ATBC cancer prevention studies

1986 - CCOP expands research to be large scale and include control groups

1987 - NCI guidelines for cervical and breast cancer screenings, cancer prevention fellowship program (CPFP)

1988 - Reagan signs Medicare Catastrophic Coverage Act (mammography screenings)

1989 - MB-CCOP (minority-based community clinical oncology program)

In the 1990s, many chemopreventative clinical trials began recruiting. Often, these studies lasted for more than a decade, so their results would be released in the early 2000s.

1991 - Chemoprevention (synthetic and natural) studies, DCPC + Produce for Better Health Foundation begins 5-A-Day message (fruit and veggie daily servings), ASSIST (smoking) initiative

1992 - Breast Cancer Prevention Trial (BCPT)

1993 - NCI mammography guidelines are dropped (controversy?), prostate lung colorectal, and ovarian cancer screening trial begins (PLCO), FOBT test for CRC mortality, CAPS (colorectal adenoma prevention), enrollment for prostate cancer trial, NCI international breast cancer screening workship

1994 - ATBC results show causal relationship between beta-carotene and lung cancer incidence in male Fins

1996 - ASCUS/LSIL Triage Study (HPV testing)

1997 - DCP and DCCPS splits from DCPC

1998 - Tamoxifen decreases breast cancer (Fisher?)

1999 - EDRN (early detection research network) and RAPID (access to prevention) established

1999 - Tamoxifen and raloxifene (STAR) clinical trials began, APC (adenoma celecoxib trial)

Due to technological advancements, improved detection of biomarkers, and increased public and governmental support for cancer prevention research, the 21st century brought large improvements in the understanding of cancer genesis and development.

2001 - Selenium and Vitamin E Cancer Prevention Trial (SELECT) Begins Recruiting Men over the age of 55 to test the effectiveness of these two dietary suppliments as prostate cancer prevention agents

2002 - Initial Results Released from the ASCUS/LSIL Triage Study (ALTS) on HPV Testing. HPV testing is found not useful for women with low-grade lesions due to the high incidence of HPV in women

2002 - National Lung Screening Trial (NLST) Begins

2002 - Results from the Colorectal Adenoma Prevention Study (CAPS) Released. Results indicate that daily use of aspirin can reduce the development of colorectal tumors by 35% in patients with a pre-existing history of polyps

2003 - Results from the Prostate Cancer Prevention Trial (PCPT) Released

2004 - August: “Decades of Progress 1983 to 2003” Published. The first 20 years of the NCI Community Clinical Oncology Program (CCOP), the precursor to the NCI Community Oncology Research Program (NCORP), are documented

2004 - Adenoma Prevention with Celecoxib (APC) Trial Suspended suspended based on an increased incidence of major cardiovascular events in participants taking celecoxib (Celebrex®)

2005 - Results of the Breast Cancer Prevention Trial (BCPT) Updated. Results show a continued reduction of invasive breast cancer incidence as well as a decrease in some negative side effects, including increased risk of stroke, pulmonary embolism, and deep vein thrombosis

2006 - Initial Results of the Study of Tamoxifen and Raloxifene (STAR) Released. Initial results show that postmenopausal women who are at increased risk of breast cancer can reduce their risk of developing the disease if they take the drug raloxifene

2008 - Initial results from the Selenium and Vitamin E Cancer Prevention Trial (SELECT) Released. Initial results indicate that selenium and vitamin E do not contribute to the prevention of prostate cancer. In fact, test results suggest a slight increase in prostate cancer incidence in subjects taking vitamin E

2009 - Prostate Results from the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial Released. Results show that screening men 55 years of age and older with PSA tests and digital rectal exams was not effective in reducing prostate cancer mortality

2010 - Early Detection Research Network (EDRN) Continues as New Grants Awarded

2010 - Alliance of Glycobiologists for Detection of Cancer Identify Key Antitumor Antibodies. They find that cancer patients produce antibodies that target abnormal proteins with sugar molecules attached made by their tumors, suggesting that antitumor antibodies in the blood may be a source of sensitive biomarkers for cancer detection

2010 - Initial Results of the Lung Cancer Screening Trial (NLST) Released. Initial results show that screening with low-dose helical computerized tomography (CT) reduced lung cancer deaths by about 20% among current and former heavy smokers

2011 - Lung Results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Released

2011 - Ovarian Results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Released. PLCO results show that screening for ovarian cancer with transvaginal ultrasound (TVU) and the CA-125 blood test did not result in fewer deaths from the disease compared with usual care

2012 - Colorectal Results from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial Released. Results confirm that screening people 55 years of age and older for colorectal cancer using flexible sigmoidoscopy reduces colorectal cancer incidence and mortality

2013 - NCI Community Oncology Research Program (NCORP) Approved for Start, opening the way for the program to bring state-of-the art cancer prevention, control, treatment and imaging clinical trials, cancer care delivery research, and disparities studies to individuals in their own communities

2013 - National Lung Screening Trial (NLST) Researchers Issue Finding on Overdiagnosis

2014 - Prevention of Early Menopause Study (POEMS) Clinical Trial Results Announced

2014 - Selenium and Vitamin E Cancer Prevention Trial (SELECT) Findings Updated. Men who had high levels of selenium at the start of the trial, as assessed by measures of selenium in their toenail clippings, had almost double the chance of developing a high-grade prostate cancer if they took the selenium supplement

2015 - Cancer Prevention and Control Central Institutional Review Board (CIRB) Established

2015 - NCORP Sites Participate in Enrolling Patients in the NCI-MATCH (Molecular Analysis for Therapy Choice) Precision Medicine Trial

2015 - Consortium on Imaging and Biomarkers is Created with Grants to Eight Principal Investigators. The consortium focuses on combining imaging methods with biomarkers to improve the accuracy of screening, early cancer detection, and diagnosis of early stage cancers

2015 - NCI Awards Grants to Create the Consortium for Molecular Characterization of Screen-Detected Lesions

2016 - The White House Announces $1 billion in Investments in the National Cancer Moonshot initiative. Prevention, including cancer vaccine development and early cancer detection, are two of the five opportunity areas

2016 - Ovarian Cancer Study Tests Lead Time of Potential Biomarkers

2016 - Largest Ever US Study to Research Causes and Genetics of Blood Diseases

2016 - Data from the Interactive Diet and Activity Tracking in AARP Study (IDATA) Are Made Available to Qualified Investigators

2016 - Olanzapine Helps Prevent Nausea and Vomiting Caused by Chemotherapy

2016 - Study Confirms Benefits of Early Palliative Care for Advanced Cancer 2016 - Think Tank Emphasizes Identifying and Creating the Next Generation of Community-Based Cancer Prevention Studies

2017 - NCI’s Cancer Prevention Fellowship Program (CPFP) Celebrates 30 Years

2017 - NCI Joins Leading Groups on Disparities Statement

2017 - TMIST Trial Aims to Provide Clarity on Breast Cancer Screening Approaches

2017 - Pre-Cancer Atlas and Other Human Tumor Atlas Network Funding Opportunity announcements Released

2017 - Experimental Ovarian Cancer Vaccine Shows Promise in Mice

See also[edit]

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