Causes of cancer

Source: Wikipedia, the free encyclopedia.
For the cellular mechanisms of cancer development, see Carcinogenesis and Oncogenomics.
Cancer requires multiple mutations to progress.

Cancer is caused by

biophysical environment (e.g. exposure to factors such as air pollution or sunlight), but also includes lifestyle and behavioral factors.[6]

Over one third of cancer deaths worldwide (and about 75–80% in the United States) are potentially avoidable by reducing exposure to known factors.[7][8] Common environmental factors that contribute to cancer death include exposure to different chemical and physical agents (tobacco use accounts for 25–30% of cancer deaths), environmental pollutants, diet and obesity (30–35%), infections (15–20%), and radiation (both ionizing and non-ionizing, up to 10%).[9] These factors act, at least partly, by altering the function of genes within cells.[10] Typically many such genetic changes are required before cancer develops.[10] Aging has been repeatedly and consistently regarded as an important aspect to consider when evaluating the risk factors for the development of particular cancers. Many molecular and cellular changes involved in the development of cancer accumulate during the aging process and eventually manifest as cancer.[11]

Genetics

Main article:
Cancer syndrome
Multiple colon polyps within the colon of an individual with familial adenomatous polyposis

Although there are over 50 identifiable hereditary forms of cancer, less than 0.3% of the population are carriers of a cancer-related genetic mutation and these make up less than 3–10% of all cancer cases.

cancer syndrome
or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predisposes the affected individuals to the development of cancers and may also cause the early onset of these cancers. Although cancer syndromes exhibit an increased risk of cancer, the risk varies. For some of these diseases, cancer is not the primary feature and is a rare consequence.

Many of the cancer syndrome cases are caused by mutations in

oncogenes and genes involved in the production of blood vessels.[12] Certain inherited mutations in the genes BRCA1 and BRCA2 with a more than 75% risk of breast cancer and ovarian cancer.[3] Some of the inherited genetic disorders that can cause colorectal cancer include familial adenomatous polyposis and hereditary non-polyposis colon cancer; however, these represent less than 5% of colon cancer cases.[13] In many cases, genetic testing
can be used to identify mutated genes or chromosomes that are passed through generations.

Gene mutations are classified as germline or somatic depending on the cell type where they appear (germline cells include the egg and the sperm and somatic cells are those forming the body). The germline mutations are carried through generations and increase the risk of cancer.[citation needed]

Cancer syndromes

Physical and chemical agents

Further information:
Safety of electronic cigarettes

Particular substances, known as

carcinogens, have been linked to specific types of cancer. Common examples of non-radioactive carcinogens are inhaled asbestos, certain dioxins, and tobacco smoke. Although the public generally associates carcinogenicity with synthetic chemicals, it is equally likely to arise in both natural and synthetic substances.[14] 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.[15] Every year, at least 200,000 people die worldwide from cancer related to their workplace.[16] 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.[16] Cancer related to one's occupation is believed to represent between 2–20% of all cases.[17] Most cancer deaths caused by occupational risk factors occur in the developed world.[16] Job stress does not appear to be a significant factor at least in lung, colorectal, breast and prostate cancers.[18]
Participation in Operation Ranchhand in Vietnam during the Vietnam war, or living near a golf course, or living on a farm would increase the risk of non-Hodgkins lymphoma due to exposure to the chemical 2,4-D. When 2,4-D is mixed with another chemical pesticide or herbicide, 2,4-T, at a 50:50 ratio, they are collectively known as Agent Orange.

Smoking

Share of cancer deaths attributed to tobacco in 2016.[19]
The incidence of lung cancer is highly correlated with smoking.

tobacco epidemic.[29]

Electronic cigarettes or

e-cigarettes are handheld electronic devices that simulate the feeling of tobacco smoking. Daily long-term use of high voltage (5.0 V) electronic cigarettes may generate formaldehyde-forming chemicals at a greater level than smoking, which was determined to be a lifetime cancer risk of approximately 5 to 15 times greater than smoking.[30] However, the overall safety and long-term health effects of electronic cigarettes is still uncertain.[31]

Materials

crystalline silica (quartz, cristobalite, and tridymite).[32] Usually, physical carcinogens must get inside the body (such as through inhaling tiny pieces) and require years of exposure to develop cancer.[32] Common occupational carcinogens include:[33]

Lifestyle

Further information: Alcohol and cancer, Diet and cancer, and Obesity and cancer

Many different lifestyle factors contribute to increasing cancer risk. Together, diet and obesity are related to approximately 30–35% of cancer deaths.[9][34] Dietary recommendations for cancer prevention typically include an emphasis on vegetables, fruit, whole grains, and fish, and avoidance of processed meat, red meat, animal fats, and refined carbohydrates.[35] The evidence to support these dietary changes is not definitive.[36]

Alcohol

Group 1 carcinogen.[37] In Western Europe 10% of cancers in males and 3% of cancers in females are attributed to alcohol.[38] Worldwide, 3.6% of all cancer cases and 3.5% of cancer deaths are attributable to alcohol.[39] In particular, alcohol use has been shown to increase the risk of developing cancers of the mouth, esophagus, pharynx, larynx, stomach, liver, ovaries, and colon.[40] The main mechanism of cancer development involves increased exposure to acetaldehyde, a carcinogen and breakdown product of ethanol.[41] Acetaldehyde induces DNA interstrand crosslinks, a form of DNA damage. These can be repaired by an inaccurate replication-coupled DNA repair pathway.[42] This repair pathway results in increased mutation frequency and altered mutational spectrum.[42] Other mechanisms have been proposed, including alcohol-related nutritional deficiencies, changes in DNA methylation, and induction of oxidative stress in tissues.[43]

Diet

Some specific foods have been linked to specific cancers.

gastric cancer. Aflatoxin B1, a frequent food contaminate, is associated with liver cancer. Betel nut chewing has been shown to cause oral cancers.[47]

The relationship between diet and the development of particular cancers may partly explain differences in cancer incidence in different countries. For example,

gastric cancer is more common in Japan due to the frequency of high-salt diets and colon cancer is more common in the United States due to the increased intake of processed and red meats.[48] Immigrant communities tend to develop the cancer risk profile of their new country, often within one to two generations, suggesting a substantial link between diet and cancer.[49][50]

When

deoxycholate was added to the food of mice so that their feces contained deoxycholate at about the same level present in feces of human on a high fat diet, 45% to 56% of the mice developed colon cancer over the next 10 months, while none of the mice on a diet without deoxycholate developed cancer.[51][52] A recent prospective human study investigating the relationship between microbial metabolites and cancer found a strong correlation between circulating deoxycholate as well as other specific bile acids and colorectal cancer risk in women.[53]

Obesity

Cancers related to obesity[54]
Men Women
Colorectal cancer Colorectal cancer
Esophageal adenocarcinoma
 Endometrial cancer
Kidney cancer
Esophageal adenocarcinoma
Pancreatic cancer Gallbladder cancer
Thyroid cancer Kidney cancer
Pancreatic cancer
Post-menopausal breast cancer

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.[34] Every year, nearly 85,000 new cancer diagnoses in the United States are related to obesity.[54] Individuals who underwent bariatric surgery for weight loss have reduced cancer incidence and mortality.[54]

There is an association between obesity and colon cancer, post-menopausal breast cancer, endometrial cancer, kidney cancer, and esophageal cancer.

progestogens).[54] Adipose tissue also creates an inflammatory environment which may contribute to the development of cancers.[56] Adipose tissue dysregulation can result in oxidative stress leading to oxidative DNA damage and cancer associated genetic instability.[57]

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.[34] More than half of the effect from diet is due to overnutrition rather than from eating too little healthy foods.[54]

Hormones

Macroscopic appearance of invasive ductal carcinoma of the breast. The tumor is the pale, crab-shaped mass at the center, surrounded by normal, yellow fatty tissue.

Some hormones play a role in the development of cancer by promoting cell proliferation.[58] Insulin-like growth factors and their binding proteins play a key role in cancer cell growth, differentiation and apoptosis, suggesting possible involvement in carcinogenesis.[59]

Hormones are important agents in sex-related cancers such as cancer of the breast, endometrium, prostate, ovary, and testis, and also of

bone cancer.[58] 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.[58] 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.[58] Men of Asian ancestry, with the lowest levels of testosterone-activating androstanediol glucuronide, have the lowest levels of prostate cancer.[58]

Other factors are also relevant: obese people have higher levels of some hormones associated with cancer and a higher rate of those cancers.

hormone replacement therapy have a higher risk of developing cancers associated with those hormones.[58] On the other hand, people who exercise far more than average have lower levels of these hormones, and lower risk of cancer.[58] Osteosarcoma may be promoted by growth hormones.[58]

Some treatments and prevention approaches leverage this cause by artificially reducing hormone levels, and thus discouraging hormone-sensitive cancers. Because steroid hormones are powerful drivers of gene expression in certain cancer cells, changing the levels or activity of certain hormones can cause certain cancers to cease growing or even undergo cell death.

aromatase inhibitors
, now have an expanding role in the treatment of breast cancer.

Infection and inflammation

Main article: Infectious causes of cancer

Worldwide, approximately 18% of cancer cases are related to

parasites
also contribute. Infectious organisms that increase the risk of cancer are frequently a source of DNA damage or genomic instability.

Viruses

HPV is the most common virus that infects the reproductive tract. Infection can lead to the development of cervical cancer in women.

Viral infection is a major risk factor for cervical and liver cancer.

Human T-cell leukemia virus-1
(T-cell leukemias).

In Western developed countries, human papillomavirus (HPV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most common oncoviruses.

tumor suppressor genes when infecting cells. In addition, the oncoproteins independently induce genomic instability in normal human cells, leading to an increased risk of cancer development.[64] Individuals with chronic hepatitis B virus infection are more than 200 times more likely to develop liver cancer than uninfected individuals.[65] Liver cirrhosis, whether from chronic viral hepatitis infection or excessive alcohol use, is independently associated with the development of liver cancer, but the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development.[65]

Bacteria and parasites

gastric carcinoma.[66] The mechanism by which H. pylori causes cancer may involve chronic inflammation or the direct action of some of the bacteria's virulence factors.[67] 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).[68] Inflammation triggered by the worm's eggs appears to be the cancer-causing mechanism. Certain parasitic infections can also increase the presence of carcinogenic compounds in the body, leading to the development of cancers.[69] Tuberculosis infection, caused by the mycobacterium M. tuberculosis, has also been linked with the development of lung cancer.[70]

Inflammation

There is evidence that inflammation itself plays an important role in the development and progression of cancer.[71] Chronic inflammation can lead to DNA damage over time and the accumulation of random genetic alterations in cancer cells.[72] Inflammation can contribute to proliferation, survival, angiogenesis and migration of cancer cells by influencing tumor microenvironment.[73] Individuals with inflammatory bowel disease are at increased risk of developing colorectal cancers.[13]

Radiation

Main article: Radiation-induced cancer

Up to 10% of invasive cancers are related to radiation exposure, including both

cellular immortality (losing normal, life-limiting cell regulatory processes), and adaptations that favor formation of a tumor.[74] Even if the radiation particle does not strike the DNA directly, it triggers responses from cells that indirectly increase the likelihood of mutations.[74]

Non-ionizing radiation

chemical bonds. 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.[75][76] However, studies have not found a consistent link between cell phone radiation and cancer risk.[77]

Higher-energy radiation, including

UVB, as the cause of most non-melanoma skin cancers, which are the most common forms of cancer in the world.[78]

Ionizing radiation

nevoid basal cell carcinoma syndrome or retinoblastoma, are more susceptible than average to developing cancer from radiation exposure.[74] Children and adolescents are twice as likely to develop radiation-induced leukemia as adults; radiation exposure before birth has ten times the effect.[74]

Ionizing radiation is also used in some kinds of medical imaging. In industrialized countries, medical imaging contributes almost as much radiation dose to the public as natural background radiation. Nuclear medicine techniques involve the injection of radioactive pharmaceuticals directly into the bloodstream. Radiotherapy deliberately deliver high doses of radiation to tumors and surrounding tissues as a form of disease treatment. 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.[80]

Residential exposure to radon gas has similar cancer risks as passive smoking.[74] Low-dose exposures, such as living near a nuclear power plant, are generally believed to have no or very little effect on cancer development.[74] 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.[74]

Rare causes

Organ transplantation

Malignant melanoma metastases in a heart.

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.[81] There have also been reports of Kaposi's sarcoma occurring after transplantation due to tumorous outgrowth of virus-infected donor cells.[82]

Trauma

See also: Marjolin's ulcer

chemicals are also present.[83]

Frequently drinking scalding hot tea may produce esophageal cancer.[83] 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.[83] However, repeated injuries to the same tissues might promote excessive cell proliferation
, which could then increase the odds of a cancerous mutation.

Maternal-fetal transmission

In the

transmissible disease. The main reason for this is tissue graft rejection caused by MHC incompatibility.[84]
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.

References

  1. PMID 29570697
    .
  2. PMID 25869442
    .
  3. ^
    S2CID 24746283.Open access icon
  4. ISBN 978-9283204299
    .
  5. ^ 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'.{{cite book}}: CS1 maint: location (link)
  6. ISBN 978-0-387-78192-1 – via Open Library
    . 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.
  7. PMID 7017215
    .
  8. PMID 27460784 – via ScienceDirect
    .
  9. ^
    PMID 18626751
    .
  10. ^
    ISBN 978-9283204299
    .
  11. ^ "Cancer Fact sheet N°297". World Health Organization. February 2014. Retrieved 10 June 2014.
  12. PMID 18196605
    .
  13. ^
    ISBN 978-9283204299
    .
  14. PMID 10686303
    .
  15. ^ "National Institute for Occupational Safety and Health- Occupational Cancer". United States National Institute for Occupational Safety and Health. Retrieved 13 October 2007.
  16. ^ a b c "WHO calls for prevention of cancer through healthy workplaces" (Press release). World Health Organization. 27 April 2007. Archived from the original on 1 May 2007. Retrieved 13 October 2007.
  17. PMID 18055160
    .
  18. PMID 23393080
    .
  19. ^ "Share of cancer deaths attributed to tobacco". Our World in Data. Retrieved 5 March 2020.
  20. ^
    PMID 15552776
    .
  21. S2CID 20891885
    .
  22. ^
    S2CID 6132726
    .
  23. ^ Cunningham FH, Fiebelkorn S, Johnson M, Meredith C. A novel application of the Margin of Exposure approach: segregation of tobacco smoke toxicants. Food Chem Toxicol. 2011 Nov;49(11):2921-33. doi: 10.1016/j.fct.2011.07.019. Epub 2011 Jul 23. PMID 21802474
  24. ^ Pu X, Kamendulis LM, Klaunig JE. Acrylonitrile-induced oxidative stress and oxidative DNA damage in male Sprague-Dawley rats. Toxicol Sci. 2009;111(1):64-71. doi:10.1093/toxsci/kfp133
  25. ^ Li L, Jiang L, Geng C, Cao J, Zhong L. The role of oxidative stress in acrolein-induced DNA damage in HepG2 cells. Free Radic Res. 2008 Apr;42(4):354-61. doi: 10.1080/10715760802008114. PMID 18404534
  26. ^
    S2CID 9172672
    .
  27. PMID 16998161
    .
  28. PMID 18434333
    .
  29. PMID 15217537
    .
  30. PMID 26164573
    .
  31. PMID 25572196
    .
  32. ^
    ISBN 978-1-55009-113-7
    . Retrieved 31 January 2011.
  33. OCLC 69672074.{{cite book}}: CS1 maint: others (link
    )
  34. ^
    S2CID 19823935
    .
  35. S2CID 2067308
    .
  36. PMID 21904992
    .
  37. ^ "IARC: IARC Strengthens its Findings on Several Carcinogenic Personal Habits and Household Exposures" (PDF). International Agency for Research on Cancer - World Health Organization. 2009.
  38. PMID 21474525
    .
  39. S2CID 14938863
    .
  40. ^ "Alcohol Consumption and the Risk of Cancer". pubs.niaaa.nih.gov. Archived from the original on 21 February 2018. Retrieved 22 March 2018.
  41. PMID 15972793
    .
  42. ^ a b Hodskinson MR, Bolner A, Sato K, Kamimae-Lanning AN, Rooijers K, Witte M, Mahesh M, Silhan J, Petek M, Williams DM, Kind J, Chin JW, Patel KJ, Knipscheer P. Alcohol-derived DNA crosslinks are repaired by two distinct mechanisms. Nature. 2020 Mar;579(7800):603-608. doi: 10.1038/s41586-020-2059-5. Epub 2020 Mar 4. PMID 32132710; PMCID: PMC7116288.
  43. PMID 15082451
    .
  44. ISBN 9789283204299
    .
  45. PMID 20374790
    .
  46. ^ "Colorectal Cancer 2011 Report: Food, Nutrition, Physical Activity, and the Prevention of Colorectal Cancer" (PDF). World Cancer Research Fund & American Institute for Cancer Research. 2011. Archived from the original (PDF) on 22 May 2019. Retrieved 22 March 2018.
  47. PMID 18990005. Archived from the original
    (PDF) on 4 September 2011. Retrieved 17 July 2014.
  48. PMID 19107449
    .
  49. S2CID 39881987
    .
  50. PMID 9081351
    .
  51. ^ Prasad AR, Prasad S, Nguyen H, Facista A, Lewis C, Zaitlin B, et al. (July 2014). "Novel diet-related mouse model of colon cancer parallels human colon cancer". World Journal of Gastrointestinal Oncology. 6 (7): 225–43. doi:10.4251/wjgo.v6.i7.225. PMC 4092339. PMID 25024814
  52. PMID 21267546
    .
  53. ^ Erikka Loftfield, PhD, MPH, Roni T Falk, MS, Joshua N Sampson, PhD, Wen-Yi Huang, PhD, Autumn Hullings, MPH, Gwen Murphy, PhD, MPH, Stephanie J Weinstein, PhD, Demetrius Albanes, MD, Neal D Freedman, PhD, MPH, Rashmi Sinha, PhD, Prospective Associations of Circulating Bile Acids and Short-Chain Fatty Acids with Incident Colorectal Cancer, JNCI Cancer Spectrum, 2022;, pkac027, https://doi.org/10.1093/jncics/pkac027
  54. ^
    PMID 21080117
    .
  55. PMID 24007864
    .
  56. PMID 23121183
    .
  57. ^ Kompella P, Vasquez KM. Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability. Mol Carcinog. 2019 Sep;58(9):1531-1550. doi: 10.1002/mc.23048. Epub 2019 Jun 5. PMID 31168912; PMCID: PMC6692207
  58. ^
    ISBN 978-1-55009-113-7
    . Retrieved 27 January 2011.
  59. PMID 19142965
    .
  60. PMID 22575588
    .
  61. S2CID 38402898
    .
  62. PMID 18626751
    .
  63. ^ "Human Papillomavirus (HPV) and Cancer". CDC. 2 January 2018. Retrieved 22 March 2018.
  64. PMID 15479788
    .
  65. ^ a b Sung MW, Thung SN, Acs G (2000). Hepatitis Viruses. BC Decker.
  66. PMID 15489139
    .
  67. PMID 16367902
    .
  68. PMID 20539059
    .
  69. ^ Mustacchi, Piero (2000). Parasites. BC Decker.
  70. PMID 23921082
    .
  71. PMID 24552665
    .
  72. PMID 19468060
    .
  73. PMID 20455855
    .
  74. ^
    ISBN 978-1-55009-113-7
    .
  75. ^ "IARC classifies radiofrequency electromagnetic fields as possibly carcinogenic to humans" (PDF). World Health Organization.
  76. ^ "IARC Monographs- Classifications". monographs.iarc.fr. Archived from the original on 10 June 2017. Retrieved 13 March 2018.
  77. ^ "Cell Phones and Cancer Risk - National Cancer Institute". Cancer.gov. 8 May 2013. Retrieved 15 December 2013.
  78. ^
    ISBN 978-1-55009-113-7
    . Retrieved 31 January 2011.
  79. PMID 27713063
    .
  80. S2CID 2760372
    .
  81. PMID 16957717
    .
  82. S2CID 2527251
    .
  83. ^
    ISBN 978-1-55009-113-7
    . Retrieved 27 January 2011.
  84. ^
    PMID 12794519
    .
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