infectious causes of cancer

Infection is the fourth most important risk factor for cancer mortality in the developed world, causing about 10% of cancer mortality (see cancer prevention), coming after tobacco (~30% of cancers), diet (~30%) and obesity (~15%). Cancer causes 22.5% of deaths in the United States,{{cite web | url=https://www.medicalnewstoday.com/articles/282929.php |title = The top 10 leading causes of death in the United States|date = 4 July 2019}} so that about 2% of mortality in the United States appears to be due to cancers caused by infections. This is comparable to mortality caused by influenza and pneumonia, which cause 2.1% of deaths in the United States.

Worldwide in 2015, the most common causes of cancer death were lung cancer (1.6 million deaths), liver cancer (745,000 deaths), and stomach cancer (723,000 deaths).{{cite journal | vauthors = Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F | title = Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012 | journal = International Journal of Cancer | volume = 136 | issue = 5 | pages = E359-86 | date = March 2015 | pmid = 25220842 | doi = 10.1002/ijc.29210 | s2cid = 6067341 | doi-access = free }} Lung cancer is largely due to non-infectious causes, such as tobacco smoke. However, liver and stomach cancer are primarily due to infectious causes. Liver cancer is largely caused by infectious hepatitis B virus (HBV) plus hepatitis C virus (HBC) and stomach cancer is largely caused by Helicobacter pylori bacteria. World-wide, the estimated number of people chronically infected with HBV and/or HCV is ~325 million.{{cite web |url=https://www.who.int/mediacentre/news/releases/2017/global-hepatitis-report/en/ |archive-url=https://web.archive.org/web/20170421134842/http://www.who.int/mediacentre/news/releases/2017/global-hepatitis-report/en/ |url-status=dead |archive-date=April 21, 2017 |title=WHO | New hepatitis data highlight need for urgent global response }} Over half of the world's population is colonized with H. pylori and it is estimated that H. pylori-positive patients have a 1-2% risk of developing distal gastric cancer.{{cite journal | vauthors = Kusters JG, van Vliet AH, Kuipers EJ | title = Pathogenesis of Helicobacter pylori infection | journal = Clinical Microbiology Reviews | volume = 19 | issue = 3 | pages = 449–90 | date = July 2006 | pmid = 16847081 | pmc = 1539101 | doi = 10.1128/CMR.00054-05 }}

Genomic instability through various means such as DNA damage and epigenetic modifications{{cite journal | vauthors = Ferguson LR, Chen H, Collins AR, Connell M, Damia G, Dasgupta S, Malhotra M, Meeker AK, Amedei A, Amin A, Ashraf SS, Aquilano K, Azmi AS, Bhakta D, Bilsland A, Boosani CS, Chen S, Ciriolo MR, Fujii H, Guha G, Halicka D, Helferich WG, Keith WN, Mohammed SI, Niccolai E, Yang X, Honoki K, Parslow VR, Prakash S, Rezazadeh S, Shackelford RE, Sidransky D, Tran PT, Yang ES, Maxwell CA | title = Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition | journal = Seminars in Cancer Biology | volume = 35 Suppl | pages = S5–S24 | date = December 2015 | issue = Suppl | pmid = 25869442 | pmc = 4600419 | doi = 10.1016/j.semcancer.2015.03.005 }} appear to be the basic causes of sporadic (non-familial) cancer. While infections have many effects, infectious organisms that increase the risk of cancer are frequently a source of DNA damage or genomic instability, as discussed below for oncogenic viruses and an oncogenic bacterium.{{citation needed|date=March 2021}}

Viruses are one of the most important risk factors for cancer development in humans.

Infection by some hepatitis viruses, especially hepatitis B and hepatitis C, can induce a long-term 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. People with chronic hepatitis B infection are more than 200 times more likely to develop liver cancer than uninfected people.{{cite book | last1 = Sung | first1 = Max W | first2 = Swan N | last2 = Thung | first3 = George | last3 = Acs | veditors = Bast RC, Kufe DW, Pollock RE | title = Holland-Frei Cancer Medicine | edition = 5th | publisher = B.C. Decker | location = Hamilton, Ontario | year = 2000 | chapter = Hepatitis Viruses | isbn = 1-55009-113-1 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK20828/ | display-editors = etal }} Liver cirrhosis, whether from chronic viral hepatitis infection or excessive alcohol use 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-Saharan Africa.{{citation needed|date=March 2021}}

Human papillomaviruses (HPV) also cause many cancers. 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 esophagus larynx, lining of the mouth, nose, and throat, anus, vulva, vagina, and penis. 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.{{cite book | last1 = McLachlin | first1 = Catherine M | first2 = Christopher P | last2 = Crum | veditors = Bast RC, Kufe DW, Pollock RE | title = Holland-Frei Cancer Medicine | edition = e.5 | publisher = B.C. Decker | location = Hamilton, Ontario | year = 2000 | chapter = Papillomaviruses and Cervical Neoplasia | isbn = 1-55009-113-1 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK20831 | display-editors = etal }}

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).{{cite book | last1 = Cohen | first1 = Jeffrey I | veditors = Bast RC, Kufe DW, Pollock RE | title = Cancer Medicine | edition = e.5 | publisher = B.C. Decker | location = Hamilton, Ontario | year = 2000 | chapter = Herpesviruses | isbn = 1-55009-113-1 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK20829/ | display-editors = etal }} EBV appears to cause all nonkeratinizing nasopharyngeal carcinomas, Epstein–Barr virus-positive diffuse large B-cell lymphomas, not otherwise specified,{{cite journal | vauthors = Grimm KE, O'Malley DP | title = Aggressive B cell lymphomas in the 2017 revised WHO classification of tumors of hematopoietic and lymphoid tissues | journal = Annals of Diagnostic Pathology | volume = 38 | pages = 6–10 | date = February 2019 | pmid = 30380402 | doi = 10.1016/j.anndiagpath.2018.09.014 | s2cid = 53196244 }} diffuse large B-cell lymphomas associated with chronic inflammation, Epstein–Barr virus-positive mucocutaneous ulcers,{{cite journal | vauthors = Ikeda T, Gion Y, Yoshino T, Sato Y | title = A review of EBV-positive mucocutaneous ulcers focusing on clinical and pathological aspects | journal = Journal of Clinical and Experimental Hematopathology | volume = 59 | issue = 2 | pages = 64–71 | date = 2019 | pmid = 31257347 | pmc = 6661964 | doi = 10.3960/jslrt.18039 }} Lymphomatoid granulomatoses{{cite journal | vauthors = Sukswai N, Lyapichev K, Khoury JD, Medeiros LJ | title = Diffuse large B-cell lymphoma variants: an update | journal = Pathology | volume = 52 | issue = 1 | pages = 53–67 | date = January 2020 | pmid = 31735345 | doi = 10.1016/j.pathol.2019.08.013 | s2cid = 208142227 }} and, in many cases, fibrin-associated diffuse large B-cell lymphoma{{cite journal | vauthors = Boyer DF, McKelvie PA, de Leval L, Edlefsen KL, Ko YH, Aberman ZA, Kovach AE, Masih A, Nishino HT, Weiss LM, Meeker AK, Nardi V, Palisoc M, Shao L, Pittaluga S, Ferry JA, Harris NL, Sohani AR | title = Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation | journal = The American Journal of Surgical Pathology | volume = 41 | issue = 3 | pages = 299–312 | date = March 2017 | pmid = 28195879 | doi = 10.1097/PAS.0000000000000775 | s2cid = 3521190 }} and intravascular NK/T cell lymphomas.{{cite journal | vauthors = Zanelli M, Mengoli MC, Del Sordo R, Cagini A, De Marco L, Simonetti E, Martino G, Zizzo M, Ascani S | title = Intravascular NK/T-cell lymphoma, Epstein-Barr virus positive with multiorgan involvement: a clinical dilemma | journal = BMC Cancer | volume = 18 | issue = 1 | pages = 1115 | date = November 2018 | pmid = 30442097 | pmc = 6238309 | doi = 10.1186/s12885-018-5001-6 | doi-access = free }} It also appears to cause some cases of lymphoma, including Burkitt's lymphoma (this causal association is especially strong in Africa) and Hodgkin's disease, EBV has 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{{cite journal | vauthors = Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS | title = Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma | journal = Science | volume = 266 | issue = 5192 | pages = 1865–9 | date = December 1994 | pmid = 7997879 | doi = 10.1126/science.7997879 | url = https://zenodo.org/record/842914 | bibcode = 1994Sci...266.1865C | s2cid = 29977325 }} causes all cases of Kaposi's sarcoma, and has been found in some cases of a cancer-related condition called Castleman's disease. Studies involving other kinds of cancer, particularly prostate cancer, have been inconsistent. Both of these herpesviruses are commonly found in cancerous cells of primary effusion lymphoma. Herpesviruses also cause cancer in animals, especially leukemias and lymphomas.

Human T cell lymphotropic virus (HTLV-1) was the first human retrovirus discovered by Robert Gallo and colleagues at NIH.{{cite journal | vauthors = Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC | title = Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 77 | issue = 12 | pages = 7415–9 | date = December 1980 | pmid = 6261256 | pmc = 350514 | doi = 10.1073/pnas.77.12.7415 | bibcode = 1980PNAS...77.7415P | doi-access = free }} The virus causes Adult T-cell leukemia, a disease first described by Takatsuki and colleagues in Japan{{cite journal | vauthors = Takatsuki K | title = Discovery of adult T-cell leukemia | journal = Retrovirology | volume = 2 | pages = 16 | date = March 2005 | pmid = 15743528 | pmc = 555581 | doi = 10.1186/1742-4690-2-16 | doi-access = free }} and other neurological diseases. Closely related to human T-cell leukemia virus, is another deltaretrovirus, bovine leukemia virus (BLV), which recently has met the expected criteria to accept a possible infectious agent causation of breast cancer, using sensitive PCR methods to detect BLV, and having samples from women with breast cancer compared to a control sample of women with no history of breast cancer.{{cite journal|vauthors=Buehring GC, Shen HM, Jensen HM, Jin DL, Hudes M, Block G|date=2 September 2015|title=Exposure to Bovine Leukemia Virus Is Associated with Breast Cancer: A Case-Control Study|journal=PLOS ONE|volume=10|issue=9|page=e0134304|doi=10.1371/journal.pone.0134304|pmc=4557937|pmid=26332838|bibcode=2015PLoSO..1034304B|doi-access=free}}{{cite journal|vauthors=Schwingel D, Andreolla AP, Erpen LM, Frandoloso R, Kreutz LC|date=27 February 2019|title=Bovine leukemia virus DNA associated with breast cancer in women from South Brazil|journal=Sci Rep|volume=9|issue=1|page=2949|doi=10.1038/s41598-019-39834-7|pmc=6393560|pmid=30814631|bibcode=2019NatSR...9.2949S}}

Merkel cell polyomavirus is the most recently discovered human cancer virus, isolated from Merkel cell carcinoma tissues in 2008,{{cite journal | vauthors = Feng H, Shuda M, Chang Y, Moore PS | title = Clonal integration of a polyomavirus in human Merkel cell carcinoma | journal = Science | volume = 319 | issue = 5866 | pages = 1096–100 | date = February 2008 | pmid = 18202256 | pmc = 2740911 | doi = 10.1126/science.1152586 | bibcode = 2008Sci...319.1096F }} 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.{{citation needed|date=March 2021}}

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.{{cite journal | vauthors = Wood C, Harrington W | title = AIDS and associated malignancies | journal = Cell Research | volume = 15 | issue = 11–12 | pages = 947–52 | year = 2005 | pmid = 16354573 | doi = 10.1038/sj.cr.7290372 | s2cid = 9498126 | doi-access = free | url = http://digitalcommons.unl.edu/cgi/viewcontent.cgi?article=1002&context=bioscivirology }} Certain other immune deficiency states (e.g. common variable immunodeficiency and IgA deficiency) are also associated with increased risk of malignancy.{{cite journal | vauthors = Mellemkjaer L, Hammarstrom L, Andersen V, Yuen J, Heilmann C, Barington T, Bjorkander J, Olsen JH | title = Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study | journal = Clinical and Experimental Immunology | volume = 130 | issue = 3 | pages = 495–500 | date = December 2002 | pmid = 12452841 | pmc = 1906562 | doi = 10.1046/j.1365-2249.2002.02004.x }}

In Western developed countries, human papillomavirus (HPV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most frequently encountered oncogenic DNA viruses.{{cite journal | vauthors = Anand P, Kunnumakkara AB, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, Lai OS, Sung B, Aggarwal BB | title = Cancer is a preventable disease that requires major lifestyle changes | journal = Pharmaceutical Research | volume = 25 | issue = 9 | pages = 2097–116 | date = September 2008 | pmid = 18626751 | pmc = 2515569 | doi = 10.1007/s11095-008-9661-9 }}{{Erratum|doi=10.1007/s11095-008-9690-4|pmid=18626751|checked=yes}}

Worldwide, HPV causes the second largest fraction of infection-associated cancers or 5.2% of the global cancer burden.{{cite journal | vauthors = Parkin DM | title = The global health burden of infection-associated cancers in the year 2002 | journal = International Journal of Cancer | volume = 118 | issue = 12 | pages = 3030–44 | date = June 2006 | pmid = 16404738 | doi = 10.1002/ijc.21731 | citeseerx = 10.1.1.623.9022 | s2cid = 10042384 }}

In the United States, HPV causes most cervical cancers, as well as some cancers of the vagina, vulva, penis, anus, rectum, and oropharynx (cancers of the back of the throat, including the base of the tongue and tonsils).{{cite web | url=https://www.cdc.gov/cancer/hpv/index.htm |title = Human Papillomavirus (HPV) and Cancer | CDC|date = 2019-08-21}} Each year in the United States, about 39,800 new cases of cancer are found in parts of the body where HPV is often found. HPV causes about 31,500 of these cancers.

As reviewed by Münger et al.{{cite journal | vauthors = Münger K, Baldwin A, Edwards KM, Hayakawa H, Nguyen CL, Owens M, Grace M, Huh K | title = Mechanisms of human papillomavirus-induced oncogenesis | journal = Journal of Virology | volume = 78 | issue = 21 | pages = 11451–60 | date = November 2004 | pmid = 15479788 | pmc = 523272 | doi = 10.1128/JVI.78.21.11451-11460.2004 }} there are about 200 HPVs. They can be classified into mucosal and cutaneous HPVs. Within each of these HPV groups, individual viruses are designated high risk or low risk according to the propensity for malignant progression of the lesions that they cause. Among the HPV high-risk viruses, the HPV E6 and E7 oncoproteins functionally inactivate the p53 and retinoblastoma tumor suppressors respectively. In addition, the high-risk HPV E6 and E7 oncoproteins can each independently induce genomic instability in normal human cells. They generate mitotic defects and aneuploidy through the induction of centrosome abnormalities.{{citation needed|date=March 2021}}

Hepatitis virus-associated hepatocarcinogenesis is a serious health concern.{{cite journal | vauthors = Takeda H, Takai A, Inuzuka T, Marusawa H | title = Genetic basis of hepatitis virus-associated hepatocellular carcinoma: linkage between infection, inflammation, and tumorigenesis | journal = Journal of Gastroenterology | volume = 52 | issue = 1 | pages = 26–38 | date = January 2017 | pmid = 27714455 | doi = 10.1007/s00535-016-1273-2 | s2cid = 20772491 | doi-access = free }} Liver cancer in the United States is primarily due to three main factors: hepatitis C virus (HCV) (22%), hepatitis B virus (HBV) (12%) and alcohol use (47%).{{cite journal | vauthors = Akinyemiju T, Abera S, Ahmed M, Alam N, Alemayohu MA, Allen C, Al-Raddadi R, Alvis-Guzman N, Amoako Y, Artaman A, Ayele TA, Barac A, Bensenor I, Berhane A, Bhutta Z, Castillo-Rivas J, Chitheer A, Choi JY, Cowie B, Dandona L, Dandona R, Dey S, Dicker D, Phuc H, Ekwueme DU, Zaki MS, Fischer F, Fürst T, Hancock J, Hay SI, Hotez P, Jee SH, Kasaeian A, Khader Y, Khang YH, Kumar A, Kutz M, Larson H, Lopez A, Lunevicius R, Malekzadeh R, McAlinden C, Meier T, Mendoza W, Mokdad A, Moradi-Lakeh M, Nagel G, Nguyen Q, Nguyen G, Ogbo F, Patton G, Pereira DM, Pourmalek F, Qorbani M, Radfar A, Roshandel G, Salomon JA, Sanabria J, Sartorius B, Satpathy M, Sawhney M, Sepanlou S, Shackelford K, Shore H, Sun J, Mengistu DT, Topór-Mądry R, Tran B, Vlassov V, Vollset SE, Vos T, Wakayo T, Weiderpass E, Werdecker A, Yonemoto N, Younis M, Yu C, Zaidi Z, Zhu L, Murray CJ, Naghavi M, Fitzmaurice C | title = The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015 | journal = JAMA Oncology | volume = 3 | issue = 12 | pages = 1683–1691 | date = December 2017 | pmid = 28983565 | pmc = 5824275 | doi = 10.1001/jamaoncol.2017.3055 }} In 2017 there will be about 40,710 new cases of liver cancer in the United States.{{cite web | url=https://www.cancer.org/cancer/liver-cancer/about/what-is-key-statistics.html |title = Key Statistics About Liver Cancer}} World-wide, liver cancer mortality is more often due to hepatitis B virus (HBV) (33%), less often due to hepatitis C virus (HCV) (21%), and still frequently due to alcohol use (30%).{{cite journal | vauthors = Wang H, Naghavi M, Allen C, Barber RM, Bhutta ZA, Carter A, etal | collaboration = GBD 2015 Mortality and Causes of Death Collaborators | title = Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980-2015: a systematic analysis for the Global Burden of Disease Study 2015 | journal = Lancet | volume = 388 | issue = 10053 | pages = 1459–1544 | date = October 2016 | pmid = 27733281 | pmc = 5388903 | doi = 10.1016/S0140-6736(16)31012-1 }} World-wide, liver cancer is the 4th most frequent cause of cancer mortality, causing 9% of all cancer mortality (total liver cancer deaths in 2015 being 810,500), and coming, in frequency, after lung, colorectal and stomach cancers.

As reviewed by Takeda et al., HCV and HBV cause carcinogenic DNA damage and genomic instability by a number of mechanisms. HBV, and especially HCV, cause chronic inflammation in the liver, increasing reactive oxygen species (ROS) formation. ROS interact directly with DNA, causing multiple types of DNA damages (26 ROS-induced DNA damages are described by Yu et al.{{cite journal | vauthors = Yu Y, Cui Y, Niedernhofer LJ, Wang Y | title = Occurrence, Biological Consequences, and Human Health Relevance of Oxidative Stress-Induced DNA Damage | journal = Chemical Research in Toxicology | volume = 29 | issue = 12 | pages = 2008–2039 | date = December 2016 | pmid = 27989142 | pmc = 5614522 | doi = 10.1021/acs.chemrestox.6b00265 }}) It also appears that chronic inflammation caused by HCV infection triggers the aberrant up-regulation of activation-induced cytidine deaminase (AID) in hepatocytes. AID creates mutations in DNA by deamination (a DNA damage) of the cytosine base, which converts cytosine into uracil. Thus, it changes a C:G base pair into a mutagenic U:G mismatch. In a still further cause of DNA damage, HCV core protein binds to the NBS1 protein and inhibits the formation of the Mre11/NBS1/Rad50 complex, thereby inhibiting DNA binding of repair enzymes.{{cite journal | vauthors = Machida K, McNamara G, Cheng KT, Huang J, Wang CH, Comai L, Ou JH, Lai MM | title = Hepatitis C virus inhibits DNA damage repair through reactive oxygen and nitrogen species and by interfering with the ATM-NBS1/Mre11/Rad50 DNA repair pathway in monocytes and hepatocytes | journal = Journal of Immunology | volume = 185 | issue = 11 | pages = 6985–98 | date = December 2010 | pmid = 20974981 | pmc = 3101474 | doi = 10.4049/jimmunol.1000618 }} As a result of reduced DNA repair mutagenic DNA damages can accumulate.{{cn|date=March 2023}}

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.{{cite journal | vauthors = Peter S, Beglinger C | title = Helicobacter pylori and gastric cancer: the causal relationship | journal = Digestion | volume = 75 | issue = 1 | pages = 25–35 | year = 2007 | pmid = 17429205 | doi = 10.1159/000101564 | s2cid = 21288653 }}{{cite journal | vauthors = Wang C, Yuan Y, Hunt RH | title = The association between Helicobacter pylori infection and early gastric cancer: a meta-analysis | journal = The American Journal of Gastroenterology | volume = 102 | issue = 8 | pages = 1789–98 | date = August 2007 | doi = 10.1111/j.1572-0241.2007.01335.x | pmid = 17521398 | s2cid = 22361105 }}{{cite journal|date=2021-03-01|title=Molecular modelling of the gastric barrier response, from infection to carcinogenesis|url=https://www.sciencedirect.com/science/article/abs/pii/S1521691821000135|journal=Best Practice & Research Clinical Gastroenterology|language=en|volume=50-51|pages=101737|doi=10.1016/j.bpg.2021.101737|issn=1521-6918|last1=Traulsen|first1=Jan|last2=Zagami|first2=Claudia|last3=Daddi|first3=Alice Anna|last4=Boccellato|first4=Francesco|pmid=33975688|s2cid=233900318}}

Although the data varies between different countries, overall about 1% to 3% of people infected with Helicobacter pylori develop gastric cancer in their lifetime compared to 0.13% of individuals who have no H. pylori infection.Kuipers EJ. Review article: exploring the link between Helicobacter pylori and gastric cancer. Alimentary Pharmacology & Therapeutics. Mar 1999 Supplement, Vol. 13, p3-11. 9p. DOI: 10.1046/j.1365-2036.1999.00002.x. (open access). Due to the prevalence of infection by H. pylori in middle-aged adults (74% in developing countries and 58% in developed countries in 2002{{cite journal | vauthors = Parkin DM | title = The global health burden of infection-associated cancers in the year 2002 | journal = International Journal of Cancer | volume = 118 | issue = 12 | pages = 3030–44 | date = June 2006 | pmid = 16404738 | doi = 10.1002/ijc.21731 | s2cid = 10042384 | doi-access = free }}), and 1% to 3% likelihood of infected individuals developing gastric cancer,{{cite journal | vauthors = Wroblewski LE, Peek RM, Wilson KT | title = Helicobacter pylori and gastric cancer: factors that modulate disease risk | journal = Clinical Microbiology Reviews | volume = 23 | issue = 4 | pages = 713–39 | date = October 2010 | pmid = 20930071 | pmc = 2952980 | doi = 10.1128/CMR.00011-10 }} H. pylori-induced gastric cancer is the third highest cause of worldwide cancer mortality as of 2018.{{cite journal | vauthors = Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Piñeros M, Znaor A, Bray F | title = Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods | journal = International Journal of Cancer | volume = 144 | issue = 8 | pages = 1941–1953 | date = April 2019 | pmid = 30350310 | doi = 10.1002/ijc.31937 | s2cid = 53034092 | doi-access = free }}

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.{{cite journal | vauthors = Hatakeyama M, Higashi H | title = Helicobacter pylori CagA: a new paradigm for bacterial carcinogenesis | journal = Cancer Science | volume = 96 | issue = 12 | pages = 835–43 | date = December 2005 | pmid = 16367902 | doi = 10.1111/j.1349-7006.2005.00130.x | s2cid = 5721063 | doi-access = free | pmc = 11159386 }}

As reviewed by Chang and Parsonnet,{{cite journal | vauthors = Chang AH, Parsonnet J | title = Role of bacteria in oncogenesis | journal = Clinical Microbiology Reviews | volume = 23 | issue = 4 | pages = 837–57 | date = October 2010 | pmid = 20930075 | pmc = 2952975 | doi = 10.1128/CMR.00012-10 }} chronic H. pylori infection in the human stomach is characterized by chronic inflammation. This is accompanied by epithelial cell release of reactive oxygen species (ROS) and reactive nitrogen species (RNOS), followed by the assembly of activated macrophages at the stomach site of infection. The macrophages also release ROS and RNOS. Levels of 8-oxo-2'-deoxyguanosine (8-OHdG), one of the predominant forms of free radical-induced oxidative DNA damages,{{cite journal | vauthors = Valavanidis A, Vlachogianni T, Fiotakis C | title = 8-hydroxy-2' -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis | journal = Journal of Environmental Science and Health. Part C, Environmental Carcinogenesis & Ecotoxicology Reviews | volume = 27 | issue = 2 | pages = 120–39 | date = April 2009 | pmid = 19412858 | doi = 10.1080/10590500902885684 | s2cid = 8109353 | url = http://www.reanimatology.com/rmt/article/view/1409 }} are increased more than 8-fold in DNA after infection by H. pylori, especially if the H. pylori are cagA positive.{{cite journal | vauthors = Raza Y, Khan A, Farooqui A, Mubarak M, Facista A, Akhtar SS, Khan S, Kazi JI, Bernstein C, Kazmi SU | title = Oxidative DNA damage as a potential early biomarker of Helicobacter pylori associated carcinogenesis | journal = Pathology & Oncology Research | volume = 20 | issue = 4 | pages = 839–46 | date = October 2014 | pmid = 24664859 | doi = 10.1007/s12253-014-9762-1 | s2cid = 18727504 }} The increase in 8-OHdG likely increases mutation.{{cite journal | vauthors = Yasui M, Kanemaru Y, Kamoshita N, Suzuki T, Arakawa T, Honma M | title = Tracing the fates of site-specifically introduced DNA adducts in the human genome | journal = DNA Repair | volume = 15 | pages = 11–20 | date = March 2014 | pmid = 24559511 | doi = 10.1016/j.dnarep.2014.01.003 | doi-access = free }} In addition, oxidative stress, with high levels of 8-OHdG in DNA, also affects genome stability by altering chromatin status. Such alterations can lead to abnormal methylation of promoters of tumor suppressor genes.{{cite journal | vauthors = Nishida N, Arizumi T, Takita M, Kitai S, Yada N, Hagiwara S, Inoue T, Minami Y, Ueshima K, Sakurai T, Kudo M | title = Reactive oxygen species induce epigenetic instability through the formation of 8-hydroxydeoxyguanosine in human hepatocarcinogenesis | journal = Digestive Diseases | volume = 31 | issue = 5–6 | pages = 459–66 | year = 2013 | pmid = 24281021 | doi = 10.1159/000355245 | s2cid = 23484545 | doi-access = free }}

In addition to mutations caused by the direct damage to DNA by H. pylori-induced ROS, H. pylori-induced carcinogenic mutations and protein expression alterations are very often a result of H. pylori-induced epigenetic alterations.{{cite journal | vauthors = Muhammad JS, Eladl MA, Khoder G | title = Helicobacter pylori-induced DNA Methylation as an Epigenetic Modulator of Gastric Cancer: Recent Outcomes and Future Direction | journal = Pathogens | volume = 8 | issue = 1 | date = February 2019 | page = 23 | pmid = 30781778 | pmc = 6471032 | doi = 10.3390/pathogens8010023 | doi-access = free }}{{cite journal | vauthors = Noto JM, Peek RM | title = The role of microRNAs in Helicobacter pylori pathogenesis and gastric carcinogenesis | journal = Frontiers in Cellular and Infection Microbiology | volume = 1 | pages = 21 | date = 2011 | pmid = 22919587 | pmc = 3417373 | doi = 10.3389/fcimb.2011.00021 | doi-access = free }} These epigenetic alterations include H. pylori-induced methylation of CpG sites in promoters of genes and H. pylori-induced altered expression of multiple microRNAs.

As reviewed by Santos and Ribeiro{{cite journal | vauthors = Santos JC, Ribeiro ML | title = Epigenetic regulation of DNA repair machinery in Helicobacter pylori-induced gastric carcinogenesis | journal = World Journal of Gastroenterology | volume = 21 | issue = 30 | pages = 9021–37 | date = August 2015 | pmid = 26290630 | pmc = 4533035 | doi = 10.3748/wjg.v21.i30.9021 | doi-access = free }} H. pylori infection is associated with epigenetically reduced efficiency of the DNA repair machinery, which favors the accumulation of mutations and genomic instability as well as gastric carcinogenesis. In particular, as reviewed by Raza et al.,{{cite journal | vauthors = Raza Y, Ahmed A, Khan A, Chishti AA, Akhter SS, Mubarak M, Bernstein C, Zaitlin B, Kazmi SU | title = Helicobacter pylori severely reduces expression of DNA repair proteins PMS2 and ERCC1 in gastritis and gastric cancer | journal = DNA Repair | volume = 89 | pages = 102836 | date = February 2020 | pmid = 32143126 | doi = 10.1016/j.dnarep.2020.102836 | s2cid = 212622031 | doi-access = free }} human gastric infection with H. pylori causes epigenetically reduced protein expression of DNA repair proteins MLH1, MGMT and MRE11. In addition, Raza et al. showed that two further DNA repair proteins, ERCC1 and PMS2 had epigenetically severely reduced protein expression once H. pylori infection had progressed to cause dyspepsia (which occurs in 20% of infected individuals{{cite journal | vauthors = Dore MP, Pes GM, Bassotti G, Usai-Satta P | title = Dyspepsia: When and How to Test for Helicobacter pylori Infection | journal = Gastroenterology Research and Practice | volume = 2016 | pages = 8463614 | date = 2016 | pmid = 27239194 | pmc = 4864555 | doi = 10.1155/2016/8463614 | doi-access = free }}).

Tuberculosis is a risk factor for lung cancer.{{cite journal | vauthors = Pallis AG, Syrigos KN | title = Lung cancer in never smokers: disease characteristics and risk factors | journal = Critical Reviews in Oncology/Hematology | volume = 88 | issue = 3 | pages = 494–503 | date = December 2013 | pmid = 23921082 | doi = 10.1016/j.critrevonc.2013.06.011 }}

Colibactin is a genotoxin produced by Escherichia coli infection that can cause colorectal cancer to develop.{{cite journal |last1=Steele |first1=Christopher D |last2=Pillay |first2=Nischalan |last3=Alexandrov |first3=Ludmil B |title=An overview of mutational and copy number signatures in human cancer |journal=The Journal of Pathology |date=July 2022 |volume=257 |issue=4 |pages=454–465 |doi=10.1002/path.5912 |pmid=35420163 |pmc=9324981 |issn=0022-3417}}

One meta-analysis of serological data comparing prior Chlamydia 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.{{cite journal | vauthors = Zhan P, Suo LJ, Qian Q, Shen XK, Qiu LX, Yu LK, Song Y | title = Chlamydia pneumoniae infection and lung cancer risk: a meta-analysis | journal = European Journal of Cancer | volume = 47 | issue = 5 | pages = 742–7 | date = March 2011 | pmid = 21194924 | doi = 10.1016/j.ejca.2010.11.003 | display-authors = etal }}{{cite journal | vauthors = Mager DL | title = Bacteria and cancer: cause, coincidence or cure? A review | journal = Journal of Translational Medicine | volume = 4 | issue = 1 | pages = 14 | date = March 2006 | pmid = 16566840 | pmc = 1479838 | doi = 10.1186/1479-5876-4-14 | doi-access = free }}{{cite journal | vauthors = Littman AJ, Jackson LA, Vaughan TL | title = Chlamydia pneumoniae and lung cancer: epidemiologic evidence | journal = Cancer Epidemiology, Biomarkers & Prevention | volume = 14 | issue = 4 | pages = 773–8 | date = April 2005 | pmid = 15824142 | doi = 10.1158/1055-9965.EPI-04-0599 | s2cid = 6510957 }}

The parasites that cause schistosomiasis (bilharzia), especially S. haematobium, can cause bladder cancer and cancer at other sites.{{cite book | last1 = Mustacchi | first1 = Piero | editor1-first = Robert C | editor1-last = Bast | editor2-first = Donald W | editor2-last = Kufe | editor3-first = Raphael E | editor3-last = Pollock | editor4-first = Ralph R | editor4-last = Weichselbaum | editor5-first = James F | editor5-last = Holland | editor6-first = Emil | editor6-last = Frei | title = Holland-Frei Cancer Medicine | edition = 5th | publisher = B.C. Decker | location = Hamilton, Ontario | year = 2000 | chapter = Parasites | isbn = 1-55009-113-1 | chapter-url = https://www.ncbi.nlm.nih.gov/books/NBK20917/ }} 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.

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

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.

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. Spirocerca lupi is associated with esophageal cancer in dogs, at least within the southern United States.

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."{{cite journal | vauthors = Muehlenbachs A, Bhatnagar J, Agudelo CA, Hidron A, Eberhard ML, Mathison BA, Frace MA, Ito A, Metcalfe MG, Rollin DC, Visvesvara GS, Pham CD, Jones TL, Greer PW, Vélez Hoyos A, Olson PD, Diazgranados LR, Zaki SR | title = Malignant Transformation of Hymenolepis nana in a Human Host | journal = The New England Journal of Medicine | volume = 373 | issue = 19 | pages = 1845–52 | date = November 2015 | pmid = 26535513 | doi = 10.1056/NEJMoa1505892 | doi-access = free }}

• Barry Marshall
• Clonally transmissible cancer
• Harald zur Hausen
• Helicobacter pylori eradication protocols
• J. Robin Warren
• List of human diseases associated with infectious pathogens
• List of oncogenic bacteria
• List of infectious diseases
• Francis Peyton Rous

{{reflist|30em}}

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

• {{Commons category-inline}}

Category:Carcinogenesis

Category:Lymphoma

Category:Viral diseases

Category:Infectious diseases