Germs That Can Cause Lymphoma

Germs linked to lymphoma include viruses, parasites and bacteria.

About 18 percent of the entire global cancer incidence may be linked to germs, according to one estimate. However, exposure to the germ, alone, is not sufficient to cause a malignancy in most cases. There are other important individual factors in play, including genes and individual differences in the body's immune response to these infections.

Lymphoma is a malignancy involving lymphocytes, a type of white blood cell.

Hodgkin’s lymphoma, or HL, and non-Hodgkin’s lymphoma, or NHL, are the two main categories of lymphoma. Germs have been linked to the development of cases of both HL and NHL. Parasites like malaria, viruses like the one that causes mono, and bacteria such as the one associated with stomach ulcers have all been implicated in the development of lymphoma.

VIRUSES:

EBV and Burkitt Lymphoma

EBV is the virus that causes mononucleosis, or mono, in teens and young adults; however, in developing countries, EBV infections that occur early in life and with fewer specific symptoms are more common. Burkitt lymphoma or BL is the most common NHL in children and adolescents around the world. The disease was named after Dr. Denis Burkitt, who was an Irish missionary surgeon who worked in Africa. Having an early infection of Epstein-Barr virus, or EBV, is been associated with Burkitt lymphoma. Having an EBV infection early life is also associated with HL and  lymphoproliferative disease after an organ transplant.

HIV and Lymphoma

Patients with HIV are predisposed to a variety of non-Hodgkin lymphomas, including Burkitt lymphoma. Burkitt lymphoma and diffuse large B-cell lymphoma, or DLBCL, are two of the most common HIV-associated lymphomas. In the cases of Burkitt lymphoma that are associated with HIV, some 30 to 50 percent of patients are also EBV-positive.

A defective immune response against EBV in HIV-positive individuals is thought to contribute to BL.

Adult T-Cell Leukemia-Lymphoma

Adult T-cell leukemia-lymphoma, or ATL, is a malignancy of the T-lymphocytes caused by human T-cell lymphotropic virus type-1, or HTLV-1. HTLV-1 is very rare in North America, but it is endemic to areas of Japan, Africa, and the Caribbean. Similar to EBV infection, most people who develop HTLV-1 do not have any recognizable symptoms of infection.

PARASITES:

Malaria and Burkitt lymphoma

Burkitt and colleagues discovered BL in 1957, where cases were clustered in regions where malaria was endemic -- the so-called lymphoma belt. However, Malaria is a parasite the infects the red blood cells, not the white blood cells of lymphoma, so the exact mechanism has been a mystery for 50 years.

In the summer of 2015, however, some light was shed on the subject, albeit in animal studies. Working in mice, researchers at Rockefeller University led by Michel Nussenzweig and colleagues  found that the same enzyme that helps make antibodies fight malaria also causes DNA damage that can lead to Burkitt’s lymphoma.

The research was published August 13 in the journal "Cell."

BACTERIA:

In addition to causing stomach ulcers, long-term infection with Helicobacter pylori, or H pylori, can cause changes in the lining of the stomach that may lead to cancer over time.

H. Pylori and MALT Lymphoma of the Stomach

A malignancy called marginal zone lymphoma of mucosa-associated lymphoid tissue is referred to as MALT, for short. Gastric MALT lymphoma is a rare type of NHL. It accounts for fewer than 1 in 20 cancers that start in the stomach. Gastric MALT lymphoma involves B-lymphocytes, a type of immune cell, in the stomach lining.

Coxiella Burnetii and Others

The bacteria that cause an infection called Q Fever -- Coxiella burnetii -- are excreted in milk, urine, and feces and present in the amniotic fluid of infected animals, according to the CDC. Cattle, sheep, and goats are the main animal culprits. Veterinarians and people who work with livestock are especially at risk. The combination of symptoms varies greatly from person to person -- and many people have no symptoms at all -- but when present, symptoms can include high fever, headache, fatigue, aches and pains, chills, nausea, vomiting, and diarrhea.

For some time, people with lymphoma were thought to be at increased risk for Q fever. Recent work reported in the October 2015 issue of the journal “Blood” suggests an association between the two diseases that goes in the other direction: investigators screened 1,468 patients treated at the French National Referral Center for Q Fever from 2004 to 2014, and found seven people who developed lymphoma after C. burnetii infection. Six patients were diagnosed with diffuse large B-cell lymphoma and one with follicular lymphoma. These and other bacteria may have a causal link to lymphoma in some cases, but research looking into this question is still ongoing.

Sources:

Coffin CS, Shaffer EA. The hot air and cold facts of dietary fiber. Canadian Journal of Gastroenterology. 2006;20(4):255-256.

Vedham V, Verma M, and Mahabir S. Early-life exposures to infectious agents and later cancer development. Cancer Medicine. 2015. [Epub ahead of print]

Parkin, D. The global health burden of infection-associated cancers in the year 2002. Int J Cancer. 2006;118:3030–3044.

Miles, R., S. Arnold, and M. Cairo. Risk factors and treatment of childhood and adolescent Burkitt lymphoma/leukemia. Br J Haematol. 2012;156:730–743.

The Rockefeller University. Science News. New research helps explain why a deadly blood cancer often affects children with malaria. Accessed October 2015.

Carbone E, Cesarman M, Spina A, et al. HIV-associated lymphomas and gamma-herpesviruses. Blood. 2009;113:1213–1224.

National Cancer Institute. Helicobacter pylori and Cancer.

Melenotte C, Million M, Audoly G, et al. Bacterium that causes Q fever linked to non-Hodgkin lymphoma. Blood. 2015

Robbiani DR, Deroubaix S, Feldhahn N et al. Plasmodium Infection Promotes Genomic Instability and AID-Dependent B Cell Lymphoma. Cell 13 August 2015; 162 (4): 727–737.

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