The two diseases have a faulty immune system in common, says rheumatologist Daniel E. Furst, MD, of the University of California, Los Angeles.  "Cancer occurs when the body's normal immune response to cancer cells, which appear in us all the time, fails. The immune system doesn’t catch something that’s abnormal. In autoimmune diseases such as RA, lupus, Sjogrens syndrome, psoriatic arthritis, myositis, sarcoidosis and scleroderma, the immune system overreacts to the normal, turning against itself," says Dr. Furst.

Those autoimmune diseases have been linked to an increased risk of cancer – lupus with lung or blood cancer; Sjogrens syndrome with lymphoma; psoriatic arthritis with skin cancer; myositis with all types of cancer; sarcoidosis with skin, liver, lung and lymphoma; and scleroderma with lung cancer. So why has RA's link to lymphoma been studied the most intensively? One reason is that many of the medications suspected of increasing the lymphoma risk are approved to treat RA but not the other autoimmune diseases. Another is that RA involves a cellular process akin to tumor growth.

In RA, the delicate lining that surrounds and protects a joint, known as the synovium, becomes inflamed, making the joint swollen and painful. As the disease progresses, the cells that make up the synovium go through a process much like what happens in cancerous tumors: Normal cells multiply unchecked and invade and destroy healthy tissue.

To complicate matters, says Dr. Furst, many drugs used to treat RA suppress the immune system, meaning the immune cells that search the body for cells gone bad aren’t able to do their job.  "If a drug suppresses not only the abnormality that’s causing the disease but also suppresses immune surveillance, one could get cancer from the therapy," he says.

That is the theory. What about the evidence? It has been accumulating for some time. The first hints that RA patients were more vulnerable to cancer surfaced in 1978, when researchers in Finland matched hospital records of patients treated for RA with patients treated for cancer and saw the overlap. That study, as well as subsequent studies of RA patients from around the world, showed a higher incidence of lymphoma, non-Hodgkins lymphoma in particular, in people with RA compared with people without RA.

By current estimates, the lymphoma risk is two to four times greater for people with rheumatoid arthritis. Cancer risk of any kind is certainly a weighty matter, but when you consider the rarity of non-Hodgkin's lymphoma – about 18 cases per 100,000 people compared with 119 per 100,000 for breast cancer and 150 per 100,000 for prostate cancer – even the elevated risk is still relatively low (less than 0.1 percent per year).

The risk is relatively low, but elevated nonetheless. Patients who have RA want answers, and researchers who study RA want to provide them. Whether it’s the RA, its treatment or some combination of the two that raises patients’ cancer risk is what medical scientists have been trying to determine ever since the 1978 Finland study.