Causes of cancer
Most cancers are related to environmental, lifestyle, or behavioral exposures. The term "environmental", as used by cancer researchers, refers to everything outside the body that interacts with humans. In this sense, the environment is not limited to the biophysical environment (e.g. exposure to factors such as air pollution or sunlight, encountered outdoors or indoors, at home or in the workplace), but also includes lifestyle, economic and behavioral factors. Common environmental factors that contribute to cancer death include tobacco (according to one estimate, accounting for 25–30% of deaths), diet and obesity[contradiction] (30–35%), infections (15–20%), radiation (both ionizing and non-ionizing, up to 10%), stress,[contradiction] lack of physical activity, and environmental pollutants.
It is nearly impossible to prove what caused a cancer in any individual, because most cancers have multiple possible causes. For example, if a person who uses tobacco heavily develops lung cancer, then it was probably caused by the tobacco use, but since everyone has a small chance of developing lung cancer as a result of air pollution or radiation, then there is a small chance that the cancer developed because of air pollution or radiation. Cancer is generally not contagious in humans, though it can be caused by oncoviruses and cancer bacteria.
Over 30% of cancers are potentially avoidable by reducing key risk factors, of which much the significant is tobacco use, which is the cause of about 22% of cancer deaths. Another 10% is due to obesity, a poor diet, lack of physical activity, and drinking alcohol. Other factors include certain infections, exposure to ionizing radiation, and environmental pollutants. In the developing world nearly 20% of cancers are due to infections such as hepatitis B, hepatitis C, and human papillomavirus. These factors act, at least partly, by changing the genes of a cell. Typically many such genetic changes are required before cancer develops. Approximately 5–10% of cancers are due to genetic defects inherited from a person's parents.
Many mutagens are also carcinogens, but some carcinogens are not mutagens. Alcohol is an example of a chemical carcinogen that is not a mutagen. In Western Europe 10% of cancers in males and 3% of cancers in females are attributed to alcohol.
Decades of research has demonstrated the link between tobacco use and cancer in the lung, larynx, head, neck, stomach, bladder, kidney, esophagus and pancreas. Tobacco smoke contains over fifty known carcinogens, including nitrosamines and polycyclic aromatic hydrocarbons. Tobacco is responsible for about one in three of all cancer deaths in the developed world, and about one in five worldwide. Lung cancer death rates in the United States have mirrored smoking patterns, with increases in smoking followed by dramatic increases in lung cancer death rates and, more recently, decreases in smoking rates since the 1950s followed by decreases in lung cancer death rates in men since 1990. However, the numbers of smokers worldwide is still rising, leading to what some organizations have described as the tobacco epidemic.
Cancer related to one's occupation is believed to represent between 2–20% of all cases. Every year, at least 200,000 people die worldwide from cancer related to their workplace. Most cancer deaths caused by occupational risk factors occur in the developed world. It is estimated that approximately 20,000 cancer deaths and 40,000 new cases of cancer each year in the U.S. are attributable to occupation. Millions of workers run the risk of developing cancers such as lung cancer and mesothelioma from inhaling asbestos fibers and tobacco smoke, or leukemia from exposure to benzene at their workplaces.
Diet and exercise
Diet, physical inactivity, and obesity are related to approximately 30–35% of cancer deaths. In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of all cancer deaths. Physical inactivity is believed to contribute to cancer risk not only through its effect on body weight but also through negative effects on immune system and endocrine system. More than half of the effect from diet is due to overnutrition rather than from eating too little healthy foods.
Diets that are low in vegetables, fruits and whole grains, and high in processed or red meats are linked with a number of cancers. A high-salt diet is linked to gastric cancer, aflatoxin B1, a frequent food contaminate, with liver cancer, and Betel nut chewing with oral cancer. This may partly explain differences in cancer incidence in different countries. For example, gastric cancer is more common in Japan due to its high-salt diet and colon cancer is more common in the United States. Immigrants develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.
Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion varies in different regions of the world from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but bacteria and parasites may also have an effect.
A virus that can cause cancer is called an oncovirus. These include human papillomavirus (cervical carcinoma), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma), and Human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in Helicobacter pylori-induced gastric carcinoma. Parasitic infections strongly associated with cancer include Schistosoma haematobium (squamous cell carcinoma of the bladder) and the liver flukes, Opisthorchis viverrini and Clonorchis sinensis (cholangiocarcinoma).
Up to 10% of invasive cancers are related to radiation exposure, including both ionizing radiation and non-ionizing ultraviolet radiation. Additionally, the vast majority of non-invasive cancers are non-melanoma skin cancers caused by non-ionizing ultraviolet radiation.
Sources of ionizing radiation include medical imaging, and radon gas. Radiation can cause cancer in most parts of the body, in all animals, and at any age, although radiation-induced solid tumors usually take 10–15 years, and can take up to 40 years, to become clinically manifest, and radiation-induced leukemias typically require 2–10 years to appear. Some people, such as those with nevoid basal cell carcinoma syndrome or retinoblastoma, are more susceptible than average to developing cancer from radiation exposure. Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect. Ionizing radiation is not a particularly strong mutagen. Residential exposure to radon gas, for example, has similar cancer risks as passive smoking. Low-dose exposures, such as living near a nuclear power plant, are generally believed to have no or very little effect on cancer development. Radiation is a more potent source of cancer when it is combined with other cancer-causing agents, such as radon gas exposure plus smoking tobacco.
Unlike chemical or physical triggers for cancer, ionizing radiation hits molecules within cells randomly. If it happens to strike a chromosome, it can break the chromosome, result in an abnormal number of chromosomes, inactivate one or more genes in the part of the chromosome that it hit, delete parts of the DNA sequence, cause chromosome translocations, or cause other types of chromosome abnormalities. Major damage normally results in the cell dying, but smaller damage may leave a stable, partly functional cell that may be capable of proliferating and developing into cancer, especially if tumor suppressor genes were damaged by the radiation. Three independent stages appear to be involved in the creation of cancer with ionizing radiation: morphological changes to the cell, acquiring cellular immortality (losing normal, life-limiting cell regulatory processes), and adaptations that favor formation of a tumor. Even if the radiation particle does not strike the DNA directly, it triggers responses from cells that indirectly increase the likelihood of mutations.
Medical use of ionizing radiation is a growing source of radiation-induced cancers. Ionizing radiation may be used to treat other cancers, but this may, in some cases, induce a second form of cancer. It is also used in some kinds of medical imaging. It is estimated that 0.4% of cancers in 2007 in the United States are due to CTs performed in the past and that this may increase to as high as 1.5–2% with rates of CT usage during this same time period.
Prolonged exposure to ultraviolet radiation from the sun can lead to melanoma and other skin malignancies. Clear evidence establishes ultraviolet radiation, especially the non-ionizing medium wave UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.
Non-ionizing radio frequency radiation from mobile phones, electric power transmission, and other similar sources have been described as a possible carcinogen by the World Health Organization's International Agency for Research on Cancer. However, studies have not found a consistent link between cell phone radiation and cancer risk.
The vast majority of cancers are non-hereditary ("sporadic cancers"). Hereditary cancers are primarily caused by an inherited genetic defect. Less than 0.3% of the population are carriers of a genetic mutation which has a large effect on cancer risk and these cause less than 3–10% of all cancer. Some of these syndromes include: certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer, and hereditary nonpolyposis colorectal cancer (HNPCC or Lynch syndrome) which is present in about 3% of people with colorectal cancer, among others.
Some substances cause cancer primarily through their physical, rather than chemical, effects on cells. A prominent example of this is prolonged exposure to asbestos, naturally occurring mineral fibers which are a major cause of mesothelioma, which is a cancer of the serous membrane, usually the serous membrane surrounding the lungs. Other substances in this category, including both naturally occurring and synthetic asbestos-like fibers such as wollastonite, attapulgite, glass wool, and rock wool, are believed to have similar effects. Non-fibrous particulate materials that cause cancer include powdered metallic cobalt and nickel, and crystalline silica (quartz, cristobalite, and tridymite). Usually, physical carcinogens must get inside the body (such as through inhaling tiny pieces) and require years of exposure to develop cancer.
Physical trauma resulting in cancer is relatively rare. Claims that breaking bones resulted in bone cancer, for example, have never been proven. Similarly, physical trauma is not accepted as a cause for cervical cancer, breast cancer, or brain cancer. One accepted source is frequent, long-term application of hot objects to the body. It is possible that repeated burns on the same part of the body, such as those produced by kanger and kairo heaters (charcoal hand warmers), may produce skin cancer, especially if carcinogenic chemicals are also present. Frequently drinking scalding hot tea may produce esophageal cancer. Generally, it is believed that the cancer arises, or a pre-existing cancer is encouraged, during the process of repairing the trauma, rather than the cancer being caused directly by the trauma. However, repeated injuries to the same tissues might promote excessive cell proliferation, which could then increase the odds of a cancerous mutation. There is no evidence that inflammation itself causes cancer, yet inflammation can contribute to proliferation, survival and migration of cancer cells by influencing the microenvironment around tumors.
Some hormones play a role in the development of cancer by promoting cell proliferation. Insulin-like growth factors and their binding proteins play a key role in cancer cell proliferation, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.
Hormones are important agents in sex-related cancers such as cancer of the breast, endometrium, prostate, ovary, and testis, and also of thyroid cancer and bone cancer. For example, the daughters of women who have breast cancer have significantly higher levels of estrogen and progesterone than the daughters of women without breast cancer. These higher hormone levels may explain why these women have higher risk of breast cancer, even in the absence of a breast-cancer gene. Similarly, men of African ancestry have significantly higher levels of testosterone than men of European ancestry, and have a correspondingly much higher level of prostate cancer. Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.
Other factors are also relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers. Women who take hormone replacement therapy have a higher risk of developing cancers associated with those hormones. On the other hand, people who exercise far more than average have lower levels of these hormones, and lower risk of cancer. Osteosarcoma may be promoted by growth hormones. Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels, and thus discouraging hormone-sensitive cancers.
Excepting the rare transmissions that occur with pregnancies and only a marginal few organ donors, cancer is generally not a transmissible disease. The main reason for this is tissue graft rejection caused by MHC incompatibility. In humans and other vertebrates, the immune system uses MHC antigens to differentiate between "self" and "non-self" cells because these antigens are different from person to person. When non-self antigens are encountered, the immune system reacts against the appropriate cell. Such reactions may protect against tumor cell engraftment by eliminating implanted cells. In the United States, approximately 3,500 pregnant women have a malignancy annually, and transplacental transmission of acute leukemia, lymphoma, melanoma and carcinoma from mother to fetus has been observed. The development of donor-derived tumors from organ transplants is exceedingly rare. The main cause of organ transplant associated tumors seems to be malignant melanoma, that was undetected at the time of organ harvest. Job stress does not appear to be a significant factor at least in lung, colorectal, breast and prostate cancers.
- Stewart, BW; Wild, CP, ed. (2014). "Cancer etiology". World Cancer Report 2014. World Health Organization. ISBN 9283204298.
- Cancer and the Environment: What you Need to Know, What You Can Do. NIH Publication No. 03-2039: National Institutes of Health. 2003.
Cancer develops over several years and has many causes. Several factors both inside and outside the body contribute to the development of cancer. In this context, scientists refer to everything outside the body that interacts with humans as 'environmental'.
- Kravchenko J, Akushevich I, Manton, KG (2009). Cancer mortality and morbidity patterns from the U. S. population: an interdisciplinary approach. Berlin: Springer. ISBN 0-387-78192-7.
The term environment refers not only to air, water, and soil but also to substances and conditions at home and at the workplace, including diet, smoking, alcohol, drugs, exposure to chemicals, sunlight, ionizing radiation, electromagnetic fields, infectious agents, etc. Lifestyle, economic and behavioral factors are all aspects of our environment.
- Anand P, Kunnumakkara AB, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB (September 2008). "Cancer is a preventable disease that requires major lifestyle changes". Pharm. Res. 25 (9): 2097–116. PMC 2515569. PMID 18626751. doi:10.1007/s11095-008-9661-9.
- "Cancer Fact sheet N°297". World Health Organization. February 2014. Retrieved 10 June 2014.
- World Cancer Report 2014. World Health Organization. 2014. pp. Chapter 1.1. ISBN 9283204298.
- "Heredity and Cancer". American Cancer Society. Retrieved July 22, 2013.
- Sasco AJ, Secretan MB, Straif K (August 2004). "Tobacco smoking and cancer: a brief review of recent epidemiological evidence". Lung Cancer. 45 Suppl 2: S3–9. PMID 15552776. doi:10.1016/j.lungcan.2004.07.998.
- Biesalski HK, Bueno de Mesquita B, Chesson A, Chytil F, Grimble R, Hermus RJ, Köhrle J, Lotan R, Norpoth K, Pastorino U, Thurnham D (1998). "European Consensus Statement on Lung Cancer: risk factors and prevention. Lung Cancer Panel". CA Cancer J Clin 48 (3): 167–76; discussion 164–6. PMID 9594919. doi:10.3322/canjclin.48.3.167.
- Seitz HK, Pöschl G, Simanowski UA (1998). "Alcohol and cancer". Recent Dev Alcohol. Recent Developments in Alcoholism 14: 67–95. ISBN 0-306-45747-4. PMID 9751943. doi:10.1007/0-306-47148-5_4.
- Schütze M, Boeing H, Pischon T, Rehm J, Kehoe T, Gmel G, Olsen A, Tjønneland AM, Dahm CC, Overvad K, Clavel-Chapelon F, Boutron-Ruault MC, Trichopoulou A, Benetou V, Zylis D, Kaaks R, Rohrmann S, Palli D, Berrino F, Tumino R, Vineis P, Rodríguez L, Agudo A, Sánchez MJ, Dorronsoro M, Chirlaque MD, Barricarte A, Peeters PH, van Gils CH, Khaw KT, Wareham N, Allen NE, Key TJ, Boffetta P, Slimani N, Jenab M, Romaguera D, Wark PA, Riboli E, Bergmann MM (2011). "Alcohol attributable burden of incidence of cancer in eight European countries based on results from prospective cohort study". BMJ 342: d1584. PMC 3072472. PMID 21474525. doi:10.1136/bmj.d1584.
- Kuper H, Boffetta P, Adami HO (September 2002). "Tobacco use and cancer causation: association by tumour type". Journal of Internal Medicine 252 (3): 206–24. PMID 12270001. doi:10.1046/j.1365-2796.2002.01022.x.
- Kuper H, Adami HO, Boffetta P (June 2002). "Tobacco use, cancer causation and public health impact". Journal of Internal Medicine 251 (6): 455–66. PMID 12028500. doi:10.1046/j.1365-2796.2002.00993.x.
- Thun MJ, Jemal A (October 2006). "How much of the decrease in cancer death rates in the United States is attributable to reductions in tobacco smoking?". Tob Control 15 (5): 345–7. PMC 2563648. PMID 16998161. doi:10.1136/tc.2006.017749.
- Dubey S, Powell CA (May 2008). "Update in lung cancer 2007". Am. J. Respir. Crit. Care Med. 177 (9): 941–6. PMC 2720127. PMID 18434333. doi:10.1164/rccm.200801-107UP.
- Proctor RN (May 2004). "The global smoking epidemic: a history and status report". Clin Lung Cancer 5 (6): 371–6. PMID 15217537. doi:10.3816/CLC.2004.n.016.
- Irigaray P, Newby JA, Clapp R, Hardell L, Howard V, Montagnier L, Epstein S, Belpomme D (December 2007). "Lifestyle-related factors and environmental agents causing cancer: an overview". Biomed. Pharmacother. 61 (10): 640–58. PMID 18055160. doi:10.1016/j.biopha.2007.10.006.
- "WHO calls for prevention of cancer through healthy workplaces" (Press release). World Health Organization. 27 April 2007. Retrieved 13 October 2007.
- "National Institute for Occupational Safety and Health- Occupational Cancer". United States National Institute for Occupational Safety and Health. Retrieved 13 October 2007.
- Kushi LH, Byers T, Doyle C, Bandera EV, McCullough M, McTiernan A, Gansler T, Andrews KS, Thun MJ (2006). "American Cancer Society Guidelines on Nutrition and Physical Activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity". CA Cancer J Clin 56 (5): 254–81; quiz 313–4. PMID 17005596. doi:10.3322/canjclin.56.5.254.
- Park S, Bae J, Nam BH, Yoo KY (2008). "Aetiology of cancer in Asia" (PDF). Asian Pac. J. Cancer Prev. 9 (3): 371–80. PMID 18990005.
- Brenner H, Rothenbacher D, Arndt V (2009). "Epidemiology of stomach cancer". Methods Mol. Biol. Methods in Molecular Biology 472: 467–77. ISBN 978-1-60327-491-3. PMID 19107449. doi:10.1007/978-1-60327-492-0_23.
- Buell P, Dunn JE (May 1965). "Cancer mortality among Japanese Issei and Nisei of California". Cancer 18 (5): 656–64. PMID 14278899. doi:10.1002/1097-0142(196505)18:5<656::AID-CNCR2820180515>3.0.CO;2-3.
- Pagano JS, Blaser M, Buendia MA, Damania B, Khalili K, Raab-Traub N, Roizman B (December 2004). "Infectious agents and cancer: criteria for a causal relation". Semin. Cancer Biol. 14 (6): 453–71. PMID 15489139. doi:10.1016/j.semcancer.2004.06.009.
- Samaras V, Rafailidis PI, Mourtzoukou EG, Peppas G, Falagas ME (May 2010). "Chronic bacterial and parasitic infections and cancer: a review" (PDF). J Infect Dev Ctries 4 (5): 267–81. PMID 20539059. doi:10.3855/jidc.819.
- Little JB (2000). "Chapter 14: Ionizing Radiation". In Kufe DW, Pollock RE, Weichselbaum RR, Bast RC Jr, Gansler TS, Holland JF, Frei E III. Cancer medicine (6th ed.). Hamilton, Ont: B.C. Decker. ISBN 1-55009-113-1.
- Brenner DJ, Hall EJ (November 2007). "Computed tomography—an increasing source of radiation exposure". N. Engl. J. Med. 357 (22): 2277–84. PMID 18046031. doi:10.1056/NEJMra072149.
- Cleaver JE, Mitchell DL (2000). "15. Ultraviolet Radiation Carcinogenesis". In Bast RC, Kufe DW, Pollock RE et al. Holland-Frei Cancer Medicine (5th ed.). Hamilton, Ontario: B.C. Decker. ISBN 1-55009-113-1. Retrieved 31 January 2011.
- "IARC classifies radiofrequency electromagnetic fields as possibly carcinogenic to humans" (PDF). World Health Organization.
- "Cell Phones and Cancer Risk - National Cancer Institute". Cancer.gov. 2013-05-08. Retrieved 2013-12-15.
- Roukos DH (April 2009). "Genome-wide association studies: how predictable is a person's cancer risk?". Expert Rev Anticancer Ther 9 (4): 389–92. PMID 19374592. doi:10.1586/era.09.12.
- Cunningham D, Atkin W, Lenz HJ, Lynch HT, Minsky B, Nordlinger B, Starling N (March 2010). "Colorectal cancer". Lancet 375 (9719): 1030–47. PMID 20304247. doi:10.1016/S0140-6736(10)60353-4.
- Maltoni CFM, Holland JF (2000). "Chapter 16: Physical Carcinogens". In Bast RC, Kufe DW, Pollock RE et al. Holland-Frei Cancer Medicine (5th ed.). Hamilton, Ontario: B.C. Decker. ISBN 1-55009-113-1. Retrieved 31 January 2011.
- Gaeta, John F (2000). "Chapter 17: Trauma and Inflammation". In Bast RC, Kufe DW, Pollock RE et al. Holland-Frei Cancer Medicine (5th ed.). Hamilton, Ontario: B.C. Decker. ISBN 1-55009-113-1. Retrieved 27 January 2011.
- Hendrik Ungefroren; Susanne Sebens; Daniel Seidl; Hendrik Lehnert; Ralf Haas (2011). "Interaction of tumor cells with the microenvironment". Cell Communication and Signaling 9 (18). doi:10.1186/1478-811X-9-18.
- Henderson BE, Bernstein L, Ross RK (2000). "Chapter 13: Hormones and the Etiology of Cancer". In Bast RC, Kufe DW, Pollock RE et al. Holland-Frei Cancer Medicine (5th ed.). Hamilton, Ontario: B.C. Decker. ISBN 1-55009-113-1. Retrieved 27 January 2011.
- Rowlands MA, Mari-Anne; , Gunnell D, Harris R, Vatten LJ, Holly JM, Martin RM (May 15, 2009). "Circulating insulin-like growth factor peptides and prostate cancer risk: a systematic review and meta-analysis". Int J Cancer. 124 (10): 2416–29. PMC 2743036. PMID 19142965. doi:10.1002/ijc.24202.
- Tolar J, Neglia JP (June 2003). "Transplacental and other routes of cancer transmission between individuals". J. Pediatr. Hematol. Oncol. 25 (6): 430–4. PMID 12794519. doi:10.1097/00043426-200306000-00002.
- Dingli D, Nowak MA (September 2006). "Cancer biology: infectious tumour cells". Nature 443 (7107): 35–6. Bibcode:2006Natur.443...35D. PMC 2711443. PMID 16957717. doi:10.1038/443035a.
- Heikkilä, K; Nyberg, ST; Theorell, T; Fransson, EI; Alfredsson, L; Bjorner, JB; Bonenfant, S; Borritz, M; Bouillon, K; Burr, H; Dragano, N; Geuskens, GA; Goldberg, M; Hamer, M; Hooftman, WE; Houtman, IL; Joensuu, M; Knutsson, A; Koskenvuo, M; Koskinen, A; Kouvonen, A; Madsen, IE; Magnusson Hanson, LL; Marmot, MG; Nielsen, ML; Nordin, M; Oksanen, T; Pentti, J; Salo, P; Rugulies, R; Steptoe, A; Suominen, S; Vahtera, J; Virtanen, M; Väänänen, A; Westerholm, P; Westerlund, H; Zins, M; Ferrie, JE; Singh-Manoux, A; Batty, GD; Kivimäki, M; IPD-Work, Consortium (Feb 7, 2013). "Work stress and risk of cancer: meta-analysis of 5700 incident cancer events in 116 000 European men and women". BMJ (Clinical research ed.) 346: f165. PMC 3567204. PMID 23393080. doi:10.1136/bmj.f165.