Blood cancers, including leukemia, lymphoma, and myeloma, arise from a combination of genetic changes, environmental exposures, infections, and age-related shifts in how your body produces blood cells. Most cases trace back to acquired mutations that accumulate over a lifetime rather than a single inherited gene, but certain exposures and conditions can dramatically raise your risk.
Acquired Mutations and Aging
The most common path to blood cancer starts with mutations that develop in blood stem cells over time. These aren’t mutations you’re born with. They accumulate as your bone marrow produces billions of new blood cells each day, and errors in DNA copying slowly build up.
One well-studied version of this process is called clonal hematopoiesis of indeterminate potential, or CHIP. In CHIP, a blood stem cell picks up a genetic change that gives it a growth advantage, causing it to produce a growing population of identical (clonal) cells. CHIP is uncommon in younger adults but becomes increasingly frequent after age 60. Most people with CHIP never develop cancer, but the condition is recognized as an early warning sign that the bone marrow is trending in a precancerous direction. The more of these driver mutations that accumulate, the higher the risk that one clone eventually becomes malignant.
This explains why blood cancers are overwhelmingly diseases of older adults. The average age at diagnosis for most leukemias and lymphomas falls between 65 and 74. The longer your bone marrow has been working, the more opportunities mutations have to stack up.
Chemical and Occupational Exposures
Benzene is the best-documented chemical cause of blood cancer, particularly acute myeloid leukemia (AML). Occupational exposure at concentrations of 10 parts per million (ppm) or higher is clearly linked to increased AML risk, and studies have detected harmful effects on blood cell production starting at concentrations as low as 2 ppm. Workers in petroleum refining, rubber manufacturing, shoe production, and chemical plants have historically faced the highest exposures. Benzene is also present in cigarette smoke and gasoline vapors, though at much lower concentrations than industrial settings.
Agricultural workers face their own set of risks. A large systematic review published by the International Agency for Research on Cancer found that occupational exposure to several classes of pesticides is positively associated with non-Hodgkin lymphoma (NHL). These include phenoxy herbicides, carbamate insecticides, organophosphorus insecticides, and the organochlorine insecticide lindane. The organophosphorus herbicide glyphosate, one of the most widely used weedkillers in the world, was specifically linked to B-cell lymphoma. Diffuse large B-cell lymphoma, the most common aggressive type of NHL, showed a particular association with phenoxy herbicide exposure.
Radiation Exposure
Ionizing radiation damages DNA directly, and blood-forming cells in the bone marrow are especially vulnerable. Studies of atomic bomb survivors, nuclear workers, and patients who received radiation therapy have consistently shown that leukemia risk rises in proportion to dose. Significant cancer risk increases appear at cumulative doses of about 100 millisieverts (0.1 sievert) or higher, with risk climbing as dose increases. For context, a single CT scan of the chest delivers roughly 7 millisieverts, so the threshold for meaningful risk involves either repeated medical imaging over time, occupational exposure, or radiation therapy.
Previous Cancer Treatment
Chemotherapy and radiation therapy can themselves cause blood cancers years later, a category known as therapy-related malignancies. In a long-term study of patients treated for Hodgkin lymphoma, the median time to developing secondary leukemia was about 5.3 years after treatment, with most cases appearing within the first decade. Some cases, however, emerged more than 20 years later.
The prognosis for treatment-related leukemia is significantly worse than for leukemia that arises on its own. In the same study, 17 of 23 patients who developed secondary leukemia died within one year of diagnosis, and the five-year survival estimate was just 4.9%. This is an important consideration when oncologists weigh the long-term risks of aggressive treatment for an initial cancer.
Viruses That Transform Blood Cells
A handful of viruses can directly drive blood cells toward cancer. The Epstein-Barr virus (EBV) is the most significant. EBV infects the majority of humans at some point in life, usually without consequence, but in certain circumstances it triggers lymphoma. The virus inserts its own genetic material into B cells (a type of immune cell) and produces proteins that hijack the cell’s growth controls. One key mechanism involves silencing the genes that normally stop a cell from multiplying unchecked, essentially removing the brakes on cell division. EBV is linked to Burkitt lymphoma, Hodgkin lymphoma, diffuse large B-cell lymphoma, and several rarer types.
The risk is far higher in people with weakened immune systems. HIV-infected individuals and organ transplant recipients on immunosuppressive drugs are especially vulnerable to EBV-driven lymphomas because their immune systems can’t keep the virus in check. HTLV-1, a less common virus found mainly in parts of Japan, the Caribbean, and Africa, directly causes a specific type called adult T-cell leukemia/lymphoma.
Inherited Genetic Syndromes
While most blood cancers stem from acquired mutations, certain inherited conditions carry strikingly elevated risk. Children with Down syndrome face a 20-fold higher risk of acute lymphoblastic leukemia (ALL) and a 150-fold higher risk of acute myeloid leukemia compared to children without the condition. About 30% of infants born with Down syndrome carry a mutation in their blood cells associated with a precancerous state called transient abnormal myelopoiesis, and 10 to 20 percent of those children go on to develop acute leukemia within four years.
Other inherited conditions that raise blood cancer risk include Fanconi anemia, a rare disorder that impairs DNA repair and leads to bone marrow failure, and Li-Fraumeni syndrome, which involves inherited mutations in a key tumor suppressor gene. These syndromes are rare, but they illustrate how foundational defects in DNA maintenance can tip the balance toward malignancy.
Smoking
Smoking increases the risk of several blood cancers, not just lung cancer. A large study found that women who smoked about 20 cigarettes a day had double the risk of Hodgkin lymphoma and certain bone marrow cancers compared to nonsmokers. Over a 10-year period, roughly 6 out of every 1,000 women who never smoked developed one of these cancers, compared to nearly 8 out of every 1,000 smokers. The likely mechanism involves benzene and other carcinogens in cigarette smoke reaching the bone marrow through the bloodstream.
Autoimmune Diseases
Chronic inflammation from autoimmune conditions is a well-established risk factor for non-Hodgkin lymphoma. A Swedish study tracking over 878,000 patients with 33 different autoimmune diseases found that 21 of those conditions significantly increased NHL risk. The overall risk was 1.6 times higher than in the general population, but some conditions carried far greater increases.
Autoimmune hemolytic anemia, a condition where the immune system destroys its own red blood cells, carried the highest risk at 27 times normal. Sjögren syndrome (4.9 times), celiac disease (4.8 times), and systemic lupus erythematosus (4.4 times) also showed strong associations. More common conditions like rheumatoid arthritis (2.0 times), Crohn’s disease (2.1 times), and psoriasis (1.4 times) carried more modest but still meaningful elevations. The connection likely stems from years of immune system overactivity driving excessive B-cell division, which creates more opportunities for cancer-causing mutations to take hold.