Estimates place the worldwide risk of cancers from infectious causes at 16.1%. Viral infections are risk factors for cervical cancer, 80% of liver cancers, and 15–20% of the other cancers. 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. ''Helicobacter pylori'' is associated with

stomach cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymp ...

, and ''

Mycobacterium ''Mycobacterium'' is a genus of over 190 species in the phylum Actinomycetota, assigned its own family, Mycobacteriaceae. This genus includes pathogens known to cause serious diseases in mammals, including tuberculosis ('' M. tuberculosis'') and ...

'', some other bacteria and

parasites Parasitism is a close relationship between species, where one organism, the parasite, lives on or inside another organism, the host, causing it some harm, and is adapted structurally to this way of life. The entomologist E. O. Wilson has c ...

also have an effect. A virus that can cause cancer is called an ''

oncovirus An oncovirus or oncogenic virus is a virus that can cause cancer. This term originated from studies of acutely transforming retroviruses in the 1950–60s, when the term "oncornaviruses" was used to denote their RNA virus origin. With the letter ...

'' or ''tumor virus''. These include the

human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

, which is associated with cervical carcinoma and

nasopharyngeal carcinoma Nasopharyngeal carcinoma (NPC), or nasopharynx cancer, is the most common cancer originating in the nasopharynx, most commonly in the postero-lateral nasopharynx or pharyngeal recess ( fossa of Rosenmüller), accounting for 50% of cases. NPC occu ...

; Epstein-Barr virus, which is associated with a variety of Epstein-Barr virus associated lymphoproliferative lymphomas;

Kaposi's sarcoma herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) is the ninth known human herpesvirus; its formal name according to the International Committee on Taxonomy of Viruses (ICTV) is ''Human gammaherpesvirus 8'', or HHV-8 in short. Like other herpesvirus ...

, which is associated with

Kaposi's sarcoma Kaposi's sarcoma (KS) is a type of cancer that can form masses in the skin, in lymph nodes, in the mouth, or in other organs. The skin lesions are usually painless, purple and may be flat or raised. Lesions can occur singly, multiply in a limit ...

and

primary effusion lymphoma Primary effusion lymphoma (PEL) is classified as a diffuse large B cell lymphoma. It is a rare malignancy of plasmablastic cells that occurs in individuals that are infected with the Kaposi's sarcoma-associated herpesvirus (i.e. KSHV/HHV8). Plasma ...

;

hepatitis B Hepatitis B is an infectious disease caused by the ''Hepatitis B virus'' (HBV) that affects the liver; it is a type of viral hepatitis. It can cause both acute and chronic infection. Many people have no symptoms during an initial infection. For ...

and

hepatitis C Hepatitis C is an infectious disease caused by the hepatitis C virus (HCV) that primarily affects the liver; it is a type of viral hepatitis. During the initial infection people often have mild or no symptoms. Occasionally a fever, dark urine, a ...

viruses which are associated with hepatocellular carcinoma; human T-cell leukemia virus-1, which is associated with

adult T-cell leukemia/lymphoma Adult T-cell leukemia/lymphoma (ATL or ATLL) is a rare cancer of the immune system's T-cells caused by human T cell leukemia/lymphotropic virus type 1 (HTLV-1). All ATL cells contain integrated HTLV-1 provirus further supporting that causal role o ...

; and

bovine leukemia virus Bovine leukemia virus (BLV) is a retrovirus which causes enzootic bovine leukosis in cattle. It is closely related to the human T‑lymphotropic virus type 1 ( HTLV-I). BLV may integrate into the genomic DNA of B‑lymphocytes as a DNA intermedi ...

, which is associated with

breast cancer Breast cancer is cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a r ...

. Bacterial infection may also increase the risk of cancer, as seen in ''

Helicobacter pylori ''Helicobacter pylori'', previously known as ''Campylobacter pylori'', is a gram-negative, microaerophilic, spiral (helical) bacterium usually found in the stomach. Its helical shape (from which the genus name, helicobacter, derives) is though ...

''-induced

. Parasitic infections strongly associated with cancer include ''

Schistosoma haematobium ''Schistosoma haematobium'' (urinary blood fluke) is a species of digenetic trematode, belonging to a group (genus) of blood flukes (''Schistosoma''). It is found in Africa and the Middle East. It is the major agent of schistosomiasis, the mos ...

'' ( squamous cell carcinoma of the bladder) and the

liver fluke Liver fluke is a collective name of a polyphyletic group of parasitic trematodes under the phylum Platyhelminthes. They are principally parasites of the liver of various mammals, including humans. Capable of moving along the blood circulation, t ...

s, ''

Opisthorchis viverrini ''Opisthorchis viverrini'', common name Southeast Asian liver fluke, is a food-borne trematode parasite from the family Opisthorchiidae that infects the bile duct. People are infected after eating raw or undercooked fish. Infection with the p ...

'' and '' Clonorchis sinensis'' (

cholangiocarcinoma Cholangiocarcinoma, also known as bile duct cancer, is a type of cancer that forms in the bile ducts. Symptoms of cholangiocarcinoma may include abdominal pain, yellowish skin, weight loss, generalized itching, and fever. Light colored stoo ...

Infection, cancer and mortality in the developed world

Infection is the fourth most important risk factor for cancer mortality in the developed world, causing about 10% of cancer mortality (see

cancer prevention Cancer prevention is the practice of taking active measures to decrease the incidence of cancer and mortality. The practice of prevention is dependent upon both individual efforts to improve lifestyle and seek preventive screening, and socioeconomi ...

), coming after tobacco (~30% of cancers), diet (~30%) and obesity (~15%). Cancer causes 22.5% of deaths in the United States, 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.

Importance of infectious causes of cancer mortality worldwide

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). 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. 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.

Genome instability due to oncogenic infections

Genomic instability Genome instability (also genetic instability or genomic instability) refers to a high frequency of mutations within the genome of a cellular lineage. These mutations can include changes in nucleic acid sequences, chromosomal rearrangements or aneu ...

through various means such as DNA damage and epigenetic modifications appear to be the basic causes of sporadic (non-familial) cancer. While

infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dis ...

s 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.

Viruses

Viruses are one of the most important risk factors for cancer development in humans. Infection by some hepatitis viruses, especially

and

, can induce a long-term viral infection that leads to

liver cancer Liver cancer (also known as hepatic cancer, primary hepatic cancer, or primary hepatic malignancy) is cancer that starts in the liver. Liver cancer can be primary (starts in liver) or secondary (meaning cancer which has spread from elsewhere to th ...

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

each year. People with chronic hepatitis B infection are more than 200 times more likely to develop liver cancer than uninfected people.

Liver cirrhosis Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...

, 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 Viral hepatitis is liver inflammation due to a viral infection. It may present in acute form as a recent infection with relatively rapid onset, or in chronic form. The most common causes of viral hepatitis are the five unrelated hepatotropic v ...

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.

Human papillomavirus Human papillomavirus infection (HPV infection) is caused by a DNA virus from the ''Papillomaviridae'' family. Many HPV infections cause no symptoms and 90% resolve spontaneously within two years. In some cases, an HPV infection persists and res ...

es (HPV) also cause many cancers. HPV is well known for causing

genital warts Genital warts are a sexually transmitted infection caused by certain types of human papillomavirus (HPV). They are generally pink in color and project out from the surface of the skin. Usually they cause few symptoms, but can occasionally be pai ...

and essentially all cases of

cervical cancer Cervical cancer is a cancer arising from the cervix. It is due to the abnormal growth of cells that have the ability to invade or spread to other parts of the body. Early on, typically no symptoms are seen. Later symptoms may include abnormal va ...

, but it can also infect and cause cancer in several other parts of the body, including the

esophagus The esophagus ( American English) or oesophagus (British English; both ), non-technically known also as the food pipe or gullet, is an organ in vertebrates through which food passes, aided by peristaltic contractions, from the pharynx to th ...

larynx The larynx (), commonly called the voice box, is an organ in the top of the neck involved in breathing, producing sound and protecting the trachea against food aspiration. The opening of larynx into pharynx known as the laryngeal inlet is about ...

, lining of the mouth, nose, and throat,

anus The anus (Latin, 'ring' or 'circle') is an opening at the opposite end of an animal's digestive tract from the mouth. Its function is to control the expulsion of feces, the residual semi-solid waste that remains after food digestion, which, de ...

vulva The vulva (plural: vulvas or vulvae; derived from Latin for wrapper or covering) consists of the external female sex organs. The vulva includes the mons pubis (or mons veneris), labia majora, labia minora, clitoris, vestibular bulbs, vulval ...

vagina In mammals, the vagina is the elastic, muscular part of the female genital tract. In humans, it extends from the vestibule to the cervix. The outer vaginal opening is normally partly covered by a thin layer of mucosal tissue called the hymen ...

, and

penis A penis (plural ''penises'' or ''penes'' () is the primary sexual organ that male animals use to inseminate females (or hermaphrodites) during copulation. Such organs occur in many animals, both vertebrate and invertebrate, but males do no ...

. 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.

Herpesvirus ''Herpesviridae'' is a large family of DNA viruses that cause infections and certain diseases in animals, including humans. The members of this family are also known as herpesviruses. The family name is derived from the Greek word ''ἕρπει� ...

es are a third group of common cancer-causing viruses. Two types of herpesviruses have been associated with cancer: the

Epstein–Barr virus The Epstein–Barr virus (EBV), formally called ''Human gammaherpesvirus 4'', is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. It is b ...

(EBV) and human herpesvirus 8 (HHV-8). EBV appears to cause all nonkeratinizing

s, Epstein–Barr virus-positive diffuse large B-cell lymphomas, not otherwise specified, diffuse large B-cell lymphomas associated with chronic inflammation, Epstein–Barr virus-positive mucocutaneous ulcers, Lymphomatoid granulomatoses and, in many cases, fibrin-associated diffuse large B-cell lymphoma and intravascular NK/T cell lymphomas. It also appears to cause some cases of lymphoma, including

Burkitt's lymphoma Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. ...

(this causal association is especially strong in Africa) and

Hodgkin's disease Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...

, 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 causes all cases of

, and has been found in some cases of a cancer-related condition called

Castleman's disease Castleman disease (CD) describes a group of rare lymphoproliferative disorders that involve enlarged lymph nodes, and a broad range of inflammatory symptoms and laboratory abnormalities. Whether Castleman disease should be considered an autoimmun ...

. Studies involving other kinds of cancer, particularly

prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that sur ...

, have been inconsistent. Both of these herpesviruses are commonly found in cancerous cells of

. Herpesviruses also cause cancer in animals, especially leukemias and lymphomas. Human T cell lymphotropic virus (

HTLV-1 Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseas ...

) was the first human

retrovirus A retrovirus is a type of virus that inserts a DNA copy of its RNA genome into the DNA of a host cell that it invades, thus changing the genome of that cell. Once inside the host cell's cytoplasm, the virus uses its own reverse transcriptase ...

discovered by

Robert Gallo Robert Charles Gallo (; born March 23, 1937) is an American biomedical researcher. He is best known for his role in establishing the human immunodeficiency virus (HIV) as the infectious agent responsible for acquired immune deficiency syndrome ...

and colleagues at

NIH The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late 1 ...

. The virus causes Adult T-cell leukemia, a disease first described by Takatsuki and colleagues in Japan 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.

Merkel cell polyomavirus Merkel cell polyomavirus (MCV or MCPyV) was first described in January 2008 in Pittsburgh, Pennsylvania. It was the first example of a human viral pathogen discovered using unbiased metagenomic next-generation sequencing with a technique called ...

is the most recently discovered human cancer virus, isolated from

Merkel cell carcinoma Merkel cell carcinoma (MCC) is a rare and aggressive skin cancer occurring in about 3 people per 1,000,000 members of the population. It is also known as cutaneous APUDoma, primary neuroendocrine carcinoma of the skin, primary small cell carcin ...

tissues in 2008, 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 The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

does not directly cause cancer, but it is associated with a number of malignancies, especially

non-Hodgkin's lymphoma Non-Hodgkin lymphoma (NHL), also known as non-Hodgkin's lymphoma, is a group of blood cancers that includes all types of lymphomas except Hodgkin lymphomas. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and tiredness ...

anal cancer Anal cancer is a cancer which arises from the anus, the distal opening of the gastrointestinal tract. Symptoms may include bleeding from the anus or a lump near the anus. Other symptoms may include pain, itchiness, or discharge from the anus. A c ...

and

. Kaposi's sarcoma is caused by human herpesvirus 8.

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...

-related cases of anal cancer and cervical cancer are commonly caused by

. After HIV destroys the immune system, the body is no longer able to control these viruses, and the infections manifest as cancer. Certain other immune deficiency states (e.g.

common variable immunodeficiency Common variable immunodeficiency (CVID) is an immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM and IgA. Symptoms generally include high susceptibility to foreign i ...

and IgA deficiency) are also associated with increased risk of malignancy.

Common oncogenic viruses

In Western developed countries,

(HPV), hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most frequently encountered oncogenic DNA viruses.

Human papillomavirus

Worldwide, HPV causes the second largest fraction of infection-associated cancers or 5.2% of the global cancer burden. 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). 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. 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.

Hepatitis B and hepatitis C viruses

Hepatitis virus-associated hepatocarcinogenesis is a serious health concern. 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%). In 2017 there will be about 40,710 new cases of liver cancer in the United States. 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%). 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 A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive substan ...

DNA damage and genomic instability by a number of mechanisms. HBV, and especially HCV, cause chronic inflammation in the liver, increasing

reactive oxygen species In chemistry, reactive oxygen species (ROS) are highly reactive chemicals formed from diatomic oxygen (). Examples of ROS include peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen. The reduction of molecular oxygen () ...

(ROS) formation. ROS interact directly with DNA, causing multiple types of DNA damages (26 ROS-induced DNA damages are described by Yu et al.) It also appears that chronic inflammation caused by HCV infection triggers the aberrant up-regulation of

activation-induced cytidine deaminase Activation-induced cytidine deaminase, also known as AICDA, AID and single-stranded DNA cytosine deaminase, is a 24 kDa enzyme which in humans is encoded by the ''AICDA'' gene. It creates mutations in DNA by deamination of cytosine base, which ...

(AID) in

hepatocyte A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, ...

s. AID creates mutations in DNA by

deamination Deamination is the removal of an amino group from a molecule. Enzymes that catalyse this reaction are called deaminases. In the human body, deamination takes place primarily in the liver, however it can also occur in the kidney. In situations of ...

(a DNA damage) of the

cytosine Cytosine () (symbol C or Cyt) is one of the four nucleobases found in DNA and RNA, along with adenine, guanine, and thymine (uracil in RNA). It is a pyrimidine derivative, with a heterocyclic aromatic ring and two substituents attached (an amin ...

base, which converts cytosine into

uracil Uracil () (symbol U or Ura) is one of the four nucleobases in the nucleic acid RNA. The others are adenine (A), cytosine (C), and guanine (G). In RNA, uracil binds to adenine via two hydrogen bonds. In DNA, the uracil nucleobase is replaced by t ...

. 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. As a result of reduced DNA repair mutagenic DNA damages can accumulate.

Bacteria

''H. pylori'', a common oncogenic bacterium

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 ''

'' and

gastric cancer Stomach cancer, also known as gastric cancer, is a cancer that develops from the lining of the stomach. Most cases of stomach cancers are gastric carcinomas, which can be divided into a number of subtypes, including gastric adenocarcinomas. Lymp ...

. 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. Due to the prevalence of infection by ''H. pylori'' in middle-aged adults (74% in developing countries and 58% in developed countries in 2002), and 1% to 3% likelihood of infected individuals developing gastric cancer, ''H. pylori''-induced gastric cancer is the third highest cause of worldwide cancer mortality as of 2018. 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 ''Helicobacter pylori'' virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa protein encoded on the 40kb ''cag'' pathogenicity island (PAI). ''H. pylori'' strains can be divided into CagA positive or negative strains. Approximately ...

has been implicated in carcinogenesis. As reviewed by Chang and Parsonnet, chronic ''H. pylori'' infection in the human stomach is characterized by chronic inflammation. This is accompanied by epithelial cell release of

(ROS) and

reactive nitrogen species Reactive nitrogen species (RNS) are a family of antimicrobial molecules derived from nitric oxide (•NO) and superoxide (O2•−) produced via the enzymatic activity of inducible nitric oxide synthase 2 ( NOS2) and NADPH oxidase respectivel ...

(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-Oxo-2'-deoxyguanosine (8-oxo-dG) is an oxidized derivative of deoxyguanosine. 8-Oxo-dG is one of the major products of DNA oxidation. Concentrations of 8-oxo-dG within a cell are a measurement of oxidative stress. In DNA Steady-state levels ...

(8-OHdG), one of the predominant forms of free radical-induced oxidative DNA damages, are increased more than 8-fold in DNA after infection by ''H. pylori'', especially if the ''H. pylori'' are

cagA ''Helicobacter pylori'' virulence factor CagA (cytotoxin-associated gene A) is a 120–145kDa protein encoded on the 40kb ''cag'' pathogenicity island (PAI). ''H. pylori'' strains can be divided into CagA positive or negative strains. Approximately ...

positive. The increase in 8-OHdG likely increases mutation. 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. 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 In biology, epigenetics is the study of stable phenotypic changes (known as ''marks'') that do not involve alterations in the DNA sequence. The Greek prefix '' epi-'' ( "over, outside of, around") in ''epigenetics'' implies features that are "o ...

alterations. These

alterations include ''H. pylori''-induced methylation of CpG sites in promoters of genes and ''H. pylori''-induced altered expression of multiple

microRNA MicroRNA (miRNA) are small, single-stranded, non-coding RNA molecules containing 21 to 23 nucleotides. Found in plants, animals and some viruses, miRNAs are involved in RNA silencing and post-transcriptional regulation of gene expression. miRN ...

s. As reviewed by Santos and Ribeiro ''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., human gastric infection with H. pylori causes epigenetically reduced protein expression of DNA repair proteins

MLH1 DNA mismatch repair protein Mlh1 or MutL protein homolog 1 is a protein that in humans is encoded by the MLH1 gene located on chromosome 3. It is a gene commonly associated with hereditary nonpolyposis colorectal cancer. Orthologs of human MLH1 ...

MGMT MGMT () is an American indie rock band formed in 2002 in Middletown, Connecticut. It was founded by multi-instrumentalists Andrew VanWyngarden and Ben Goldwasser. Alongside VanWyngarden and Goldwasser, MGMT's live lineup currently consists o ...

and

MRE11 Double-strand break repair protein MRE11 is an enzyme that in humans is encoded by the ''MRE11'' gene. The gene has been designated ''MRE11A'' to distinguish it from the pseudogene ''MRE11B'' that is nowadays named ''MRE11P1''. Function This ge ...

. In addition, Raza et al. showed that two further DNA repair proteins,

ERCC1 DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ''ERCC1'' gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination. Many aspects of these two gen ...

and

PMS2 Mismatch repair endonuclease PMS2 is an enzyme that in humans is encoded by the ''PMS2'' gene. Function This gene is one of the PMS2 gene family members which are found in clusters on chromosome 7. Human PMS2 related genes are located at bands ...

had epigenetically severely reduced protein expression once ''H. pylori'' infection had progressed to cause

dyspepsia Indigestion, also known as dyspepsia or upset stomach, is a condition of impaired digestion. Symptoms may include upper abdominal fullness, heartburn, nausea, belching, or upper abdominal pain. People may also experience feeling full earlier ...

(which occurs in 20% of infected individuals).

''Mycobacterium''

Tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in w ...

is a risk factor for

lung cancer Lung cancer, also known as lung carcinoma (since about 98–99% of all lung cancers are carcinomas), is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung. Lung carcinomas derive from transformed, malignan ...

Other bacteria

One

meta-analysis A meta-analysis is a statistical analysis that combines the results of multiple scientific studies. Meta-analyses can be performed when there are multiple scientific studies addressing the same question, with each individual study reporting me ...

serological Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. Such antibodies are typically formed in response to an infection (against a given mi ...

data comparing prior ''

Chlamydia pneumoniae ''Chlamydia pneumoniae'' is a species of ''Chlamydia'', an obligate intracellular bacterium that infects humans and is a major cause of pneumonia. It was known as the Taiwan acute respiratory agent (TWAR) from the names of the two original isola ...

'' infection in patients with and without lung cancer found results suggesting prior infection was associated with a slightly increased risk of developing lung cancer.

Parasites

The parasites that cause

schistosomiasis Schistosomiasis, also known as snail fever, bilharzia, and Katayama fever, is a disease caused by parasitic flatworms called schistosomes. The urinary tract or the intestines may be infected. Symptoms include abdominal pain, diarrhea, bloody ...

(bilharzia), especially '' S. haematobium'', can cause

bladder cancer Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mal ...

and cancer at other sites. 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 Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel m ...

. Distomiasis, caused by parasitic

s, is associated with

(cancer of the

bile duct A bile duct is any of a number of long tube-like structures that carry bile, and is present in most vertebrates. Bile is required for the digestion of food and is secreted by the liver into passages that carry bile toward the hepatic duct. It ...

) in East Asia.

Malaria Malaria is a Mosquito-borne disease, mosquito-borne infectious disease that affects humans and other animals. Malaria causes Signs and symptoms, symptoms that typically include fever, fatigue (medical), tiredness, vomiting, and headaches. In se ...

is associated with

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 Esophageal cancer is cancer arising from the esophagus—the food pipe that runs between the throat and the stomach. Symptoms often include difficulty in swallowing and weight loss. Other symptoms may include pain when swallowing, a hoarse voic ...

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 Malignant transformation is the process by which cells acquire the properties of cancer. This may occur as a primary process in normal tissue, or secondarily as ''malignant degeneration'' of a previously existing benign tumor. Causes There are ...

, 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 Public health is "the science and art of preventing disease, prolonging life and promoting health through the organized efforts and informed choices of society, organizations, public and private, communities and individuals". Analyzing the det ...

but is interesting for being "a novel disease mechanism that links infection and cancer."

References

;Bibliography *

External links

* {{Commons category-inline Carcinogenesis Lymphoma Viral diseases Infectious diseases