Infectious causes of cancer

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Helicobacter pylori

Estimates place the worldwide risk of cancers from infectious causes at 16.1%.[1] Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers.[2] This proportion varies in different regions of the world from a high of 32.7% in Sub-Saharan Africa to 3.3% in Australia and New Zealand.[1] Viruses are the usual infectious agents that cause cancer but Mycobacterium, some other bacteria and parasites 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.[3] 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).[4]

Mycobacterium

Tuberculosis is a risk factor for lung cancer.[5]

Viruses

Viruses are one of the most important risks factor for cancer development in humans.[2]

Infection by some hepatitis viruses, especially hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer in about 1 in 200 of people infected with hepatitis B each year (more in Asia, fewer in North America), and in about 1 in 45 of people infected with hepatitis C each year.[6] People with chronic hepatitis B infection are more than 200 times more likely to develop liver cancer than uninfected people.[6] Liver cirrhosis, whether from chronic viral hepatitis infection or alcohol abuse or some other cause, is independently associated with the development of liver cancer, and the combination of cirrhosis and viral hepatitis presents the highest risk of liver cancer development. Because chronic viral hepatitis is so common, and liver cancer so deadly, liver cancer is one of the most common causes of cancer-related deaths in the world, and is especially common in East Asia and parts of sub-Sarahan Africa.

Human papillomaviruses (HPV) are another particularly common cancer-causing virus. HPV is well known for causing genital warts and essentially all cases of cervical cancer, but it can also infect and cause cancer in several other parts of the body, including the larynx, lining of the mouth, nose, and throat, anus, and esophagus. The Papanicolaou smear ("Pap" smear) is a widely used cancer screening test for cervical cancer. DNA-based tests to identify the virus are also available.[7]

Herpesviruses are a third group of common cancer-causing viruses. Two types of herpesviruses have been associated with cancer: the Epstein-Barr virus (EBV) and human herpesvirus 8 (HHV-8).[8] EBV appears to cause all nonkeratinizing nasopharyngeal carcinomas and some cases of lymphoma, including Burkitt’s lymphoma—the association is especially strong in Africa—and Hodgkin’s disease.[8] EBV has also been found in a variety of other types of cancer cells, although its role in causing these other cancers is not well established. KSHV/HHV-8[9] causes all cases of Kaposi’s sarcoma, and has been found in some cases of a cancer-related condition called Castleman's disease.[8] Studies involving other kinds of cancer, particularly prostate cancer, have been inconsistent.[8] Both of these herpesviruses are commonly found in cancerous cells of primary effusion lymphoma.[8] Herpesviruses also cause cancer in animals, especially leukemias and lymphomas.[8]

Human T cell lymphotropic virus (HTLV-1) was the first human retrovirus discovered by Robert Gallo and colleagues at NIH.[10] The virus causes Adult T cell leukemia, a disease first described by Takatsuki and colleagues in Japan [11] and other neurological diseases.

Merkel cell polyomavirus is the most recently discovered human cancer virus, isolated from Merkel cell carcinoma tissues in 2008,[12] by the same group that discovered KSHV/HHV-8 in 1994, using a new technology called digital transcriptome subtraction. About 80% of Merkel cell carcinomas are caused by Merkel cell polyomavirus; the remaining tumors have an unknown etiology and possibly a separate histogenesis. This is the only member of this group of viruses known to cause human cancer but other polyomaviruses are suspects for being additional cancer viruses.

HIV does not directly cause cancer, but it is associated with a number of malignancies, especially Kaposi's sarcoma, non-Hodgkin's lymphoma, anal cancer and cervical cancer. Kaposi's sarcoma is caused by human herpesvirus 8. AIDS-related cases of anal cancer and cervical cancer are commonly caused by human papillomavirus. After HIV destroys the immune system, the body is no longer able to control these viruses, and the infections manifest as cancer.[13] Certain other immune deficiency states (e.g. common variable immunodeficiency and IgA deficiency) are also associated with increased risk of malignancy.[14]

Bacteria

In addition to viruses, certain kinds of bacteria can cause some cancers. The most prominent example is the link between chronic infection of the wall of the stomach with Helicobacter pylori and gastric cancer.[15][16] Although only a minority of those infected with Helicobacter go on to develop cancer, since this bacterial infection is quite common, it may be responsible for most of these cancers.[17] The mechanism by which H. pylori causes cancer may involve chronic inflammation, or the direct action of some of its virulence factors, for example, CagA has been implicated in carcinogenesis.[18]

C. pneumoniae infection has been found to cause to lung cancer. One meta-analysis of serological data comparing prior C. pneumoniae infection in patients with and without lung cancer found results suggesting prior infection was associated with a slightly increased risk of developing lung cancer.[19][20][21]

Mycoplasma species also have been found to cause cancer.[22][23]

Parasites

The parasites that cause schistosomiasis (bilharzia), especially S. haematobium, can cause bladder cancer and cancer at other sites.[24] Inflammation triggered by the worm's eggs appears to be the mechanism by which squamous cell carcinoma of the bladder is caused. In Asia, infection by S. japonicum is associated with colorectal cancer.[24]

Distomiasis, caused by parasitic liver flukes, is associated with cholangiocarcinoma (cancer of the bile duct) in East Asia.[24]

Malaria is associated with Burkitt's lymphoma in Africa, especially when present in combination with Epstein-Barr virus, although it is unclear whether it is causative.[24]

Parasites are also a significant cause of cancer in animals. Cysticercus fasciolaris, the larval form of the common tapeworm of the cat, Taenia taeniaformis, causes cancer in rats.[24] Spirocerca lupi is associated with esophageal cancer in dogs, at least within the southern United States.[24]

A novel type of case, reported in 2015, involved an immunocompromised man whose tapeworm underwent malignant transformation, causing metastasis of tapeworm cell neoplasia throughout his body. This was not a cancer of his own cells but of the parasite's. This isolated case has no substantive bearing on public health but is interesting for being "a novel disease mechanism that links infection and cancer."[25]

See also

Further reading

  • Cornwall, Claudia M. Catching cancer : the quest for its viral and bacterial causes. Lanham: Rowman & Littlefield Publishers, 2013.

References

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