What is azathioprine? Does it cause cancer?

Exposure routes: Ingestion, intravenous injection, and inhalation

Where found: The drug is found in hospitals, used for transplant and autoimmune disease patients, and in manufacturing plants that make and package the drug.

At risk: Patients who take azathioprine and workers who manufacture it.

Etiology and symptoms of associated cancers: In the liver, azathioprine is converted to 6-mercaptopurine, which inhibits deoxyribonucleic acid (DNA) synthesis. This suppresses the immune system but can also cause a dangerous decrease in the number of white blood cells (leukopenia) and platelets (thrombocytopenia), increased risk of infection and bleeding, gastrointestinal disturbances, and liver damage. The substance 6-mercaptopurine also inserts between adjacent nucleotide bases in DNA molecules and causes mutations that lead to various types of cancer.

Azathioprine increases the risk of developing squamous cell carcinoma, a type of skin cancer that appears as persistent wartlike growths, scaly patches, or open sores that crust over and bleed; non-Hodgkin lymphoma, a blood-based cancer of white blood cells called T cells, the most common symptoms of which are painless swelling of the neck or underarm lymph nodes, unexplained fever, loss of weight and appetite, itchy skin with reddened patches, and constant fatigue; and cancer of the bile ducts or hepatobiliary carcinomas, whose symptoms include jaundice, itching, stomach pain, weight loss, and fever.

History: The pioneer of liver transplantation, Sir Roy Yorke Calne, first used azathioprine to prevent organ rejection in liver transplant patients. Azathioprine was the standard antirejection drug in the 1970s for organ transplants and was later enlisted to treat patients who suffer from diseases that result when the immune system attacks the patient’s own body (autoimmune diseases).

Several epidemiological studies have shown that transplant patients who took azathioprine were at a high risk for different types of tumors. Other patients who took azathioprine but were not transplant patients, including those with rheumatoid arthritis, systemic lupus, inflammatory bowel disease, and certain skin and renal diseases, have also shown higher incidences of such malignancies, but not as high as those observed in transplant patients, since the dosages to treat autoimmune diseases are lower than those used for transplant patients. Mycophenolate mofetil, which is not as carcinogenic, is gradually replacing azathioprine as the antirejection drug of choice.

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