Lymphoma develops when white blood cells called lymphocytes acquire genetic changes that make them grow uncontrollably instead of dying on schedule. There is no single cause. Instead, a combination of factors can push these immune cells toward becoming cancerous, including infections, chemical exposures, immune system problems, inherited genetics, and body weight.
How Normal Immune Cells Become Cancerous
Lymphocytes, particularly B cells, are uniquely vulnerable to becoming cancerous because of how they normally function. To fight infections, B cells constantly reshuffle their DNA to produce different antibodies. That reshuffling process can go wrong, creating chromosomal breaks and mutations that activate genes promoting cell growth or disable genes that normally keep growth in check.
Once a lymphocyte picks up the right combination of mutations, it essentially hijacks its own survival signals. Normal B cells receive chemical signals telling them when to grow and when to die. Mutated cells can flip these signals to “always on,” keeping themselves alive indefinitely and dividing without restraint. Many lymphomas share a common feature: they activate a molecular pathway that blocks programmed cell death, allowing damaged cells to accumulate rather than self-destruct the way healthy cells would.
Other mutations alter the way DNA is packaged inside the cell, changing which genes get turned on or off. This rewiring of gene expression can transform a cell that was supposed to patrol for infections into one that builds a tumor.
Viral and Bacterial Infections
Certain chronic infections directly contribute to lymphoma by keeping immune cells in a state of constant activation, giving mutations more opportunities to occur.
Epstein-Barr virus (EBV), the virus behind mononucleosis, is the most well-established viral trigger. EBV infects B cells and produces proteins that prevent those cells from dying, even after they’ve acquired dangerous mutations. In people with weakened immune systems, EBV-driven B cell proliferation leads to an accumulation of genetic errors, particularly a specific chromosomal rearrangement that causes explosive cell growth. This is the primary mechanism behind Burkitt lymphoma, an aggressive form most common in sub-Saharan Africa where co-infection with malaria reactivates latent EBV and further suppresses immune surveillance. Nearly all cases of endemic Burkitt lymphoma are associated with EBV, though only a small proportion of cases in Western countries show evidence of the virus.
On the bacterial side, chronic stomach infection with Helicobacter pylori is a proven cause of a lymphoma type that forms in the stomach lining. The persistent infection creates ongoing immune stimulation that forces B cells to keep dividing in response to bacterial proteins. Over time, this sustained stimulation favors the emergence of malignant clones. The connection is so direct that eradicating the bacteria with antibiotics causes the lymphoma to regress in 60% to 90% of patients. If the infection returns, the lymphoma can reappear and progress more quickly because the precancerous cells are already primed.
Immune Suppression and Autoimmune Disease
Anything that chronically disrupts normal immune function raises lymphoma risk. Organ transplant recipients, who take medications to prevent rejection, develop lymphoma at roughly 28 times the rate of the general population. Most of these lymphomas are linked to EBV, because the suppressed immune system can no longer keep the virus in check.
Autoimmune diseases pose a different but related risk. Sjögren’s syndrome, a condition that attacks moisture-producing glands, carries the highest lymphoma risk of any autoimmune disease, with patients facing 7 to 15 times the risk of the general population. The mechanism is a slow, stepwise process. Chronic inflammation in the salivary glands creates clusters of immune cells that behave like miniature lymph nodes. Inside these structures, B cells undergo repeated rounds of mutation as they respond to the body’s own tissues. Over years, some of those B cells accumulate enough genetic damage to escape normal growth controls entirely. The lymphomas that develop in Sjögren’s patients frequently originate from B cells that were producing a specific type of antibody called rheumatoid factor, suggesting that the autoimmune response itself seeds the cancer.
HIV infection also significantly increases lymphoma risk, both by suppressing immune surveillance and by allowing EBV to proliferate unchecked.
Chemical and Occupational Exposures
Benzene is the best-documented chemical risk factor for lymphoma. A large Swiss study tracking workers across different industries found that lymphoma risk increased in a dose-dependent pattern: the more benzene exposure someone had, the higher their risk of developing diffuse large B-cell lymphoma and follicular lymphoma, the two most common non-Hodgkin subtypes. Workers in petroleum refining, rubber manufacturing, and chemical production historically faced the highest exposures, though workplace levels have declined significantly since the mid-20th century.
The link between the herbicide glyphosate (the active ingredient in Roundup) and lymphoma has been heavily debated. A meta-analysis pooling results from seven studies found no overall increased risk of non-Hodgkin lymphoma with glyphosate use. However, the picture gets more complicated at higher exposure levels. Among people with the heaviest use, the pooled risk estimate was 1.49 times higher than unexposed individuals, though the statistical uncertainty was wide enough that this could reflect chance. One study found that people using glyphosate more than two days per year had roughly double the risk. Notably, when researchers separated glyphosate from other pesticides, the risk from glyphosate alone largely disappeared, suggesting that combined chemical exposures may matter more than any single herbicide.
Family History and Inherited Genes
Most lymphomas are not inherited, but having a first-degree relative with lymphoma does modestly increase your risk. Several inherited gene variants have been identified in lymphoma patients, most notably in genes already known to cause hereditary cancer syndromes. Mutations in TP53 cause Li-Fraumeni syndrome, which predisposes people to a wide range of cancers including lymphoma. Inherited changes in CHEK2 and PALB2, genes more commonly associated with breast cancer risk, have also been found in lymphoma patients at higher-than-expected rates.
These hereditary cases are rare. For the vast majority of lymphoma patients, the critical genetic mutations are acquired over a lifetime rather than inherited at birth.
Body Weight
Obesity, particularly obesity that starts early in life, is an underappreciated risk factor. A pooled analysis of six large U.S. studies found that people who were obese in young adulthood and stayed obese had 2.67 times the risk of developing diffuse large B-cell lymphoma compared to people who maintained a healthy weight. The researchers estimated that up to 23.5% of all diffuse large B-cell lymphomas could potentially be prevented if young adult obesity were avoided. The mechanism likely involves chronic low-grade inflammation that obesity produces throughout the body, creating a persistent state of immune activation similar to what infections and autoimmune diseases cause.
Age and Sex
Non-Hodgkin lymphoma, which accounts for about 90% of all lymphoma diagnoses, is primarily a disease of older adults. The median age at diagnosis is 68. Men develop it at notably higher rates than women: 22.4 new cases per 100,000 men compared to 15.7 per 100,000 women each year. The reasons for this gap are not fully understood but likely involve differences in immune function, occupational exposures, and hormonal factors. Hodgkin lymphoma follows a different pattern, with a peak in young adults between ages 15 and 35 and a second, smaller peak after age 55.
Non-Hodgkin lymphoma is also more common among non-Hispanic white populations than other racial and ethnic groups in the United States, though the reasons remain unclear.