The association between rheumatoid arthritis (RA) and cancer is not completely clear. Some studies show an increased risk of cancer in people with rheumatoid arthritis (RA) while others show a decreased risk. But the picture becomes clearer when researchers look at specific cancer types.

Lymphoma. The strongest evidence of a link appears to be between lymphoma — the most common type of blood cancer — and severe rheumatoid arthritis (RA). Researchers from Sweden examined data from nearly 75,000 RA patients, 378 of whom had lymphoma. The researchers assessed risk for three different levels of disease activity (low, moderate, and severe) and found that people with moderate disease activity were eight times more likely to have lymphoma than those who had low disease activity, while those with severe disease activity were 70 times more likely.

More support for a connection comes from a review of 21 published studies, including the Swedish study and 13 others that tried to determine whether there was a link between lymphoma and rheumatoid arthritis (RA). The findings, reported recently in Arthritis Research & Therapy, showed that overall, people with rheumatoid arthritis (RA) were twice as likely as the general population to develop lymphoma, particularly Hodgkin’s lymphoma (one of the most curable types of cancer when detected early).

Lung cancer. The same review also reported that lung cancer was observed more often in people with rheumatoid arthritis (RA). Based on data from 12 studies, people with rheumatoid arthritis (RA) were 63% more likely to develop lung cancer than the general population.

Cancer at other sites. In addition, the authors of the review reported a potentially reduced risk of colorectal cancer among people with rheumatoid arthritis (RA) — possibly due to their increased use of nonsteroidal antiinflammatory drugs (NSAIDs) and COX-2 inhibitors. The researchers also reported a slightly reduced risk of breast cancer.

What’s Behind the Link? An important question that remains unanswered is whether people with rheumatoid arthritis (RA) are more prone to develop certain cancers than others or if the medications they take could be responsible for the increased risk.

In the Swedish study, more than 70% of people with rheumatoid arthritis (RA) had taken traditional disease-modifying antirheumatic drugs, or DMARDs, such as methotrexate (Rheumatrex, Trexall). However, the only DMARD linked to an increased risk of lymphoma was azathioprine (Imuran) — a treatment that is rarely used today. There was also no link between NSAIDs like aspirin and ibuprofen (Advil and others).

One encouraging finding was that people who frequently used corticosteroids for inflamed joints had a lower risk of lymphoma, a result that suggests anti-inflammatory drugs could possibly protect against lymphoma.

No participants in the Swedish study were taking the newer DMARDs, called biologic response modifiers (BRMs). However, in a review of nine clinical trials published in the Journal of the American Medical Association, researchers reported that two BRMs — infliximab (Remicade) and adalimumab (Humira) — were associated with an increased risk of certain malignancies, most notably lymphoma and skin cancer, compared with placebo. (No other drugs in this class were studied). A possible explanation: Both Remicade and Humira as well as etanercept (Enbrel) block a protein called tumor necrosis factor (TNF), which plays an important role in controlling tumor growth.

Bottom line advice: Multiple studies show a trend toward a higher risk of certain cancers among people with rheumatoid arthritis (RA). Although the reasons for these connections are not yet fully understood, evidence suggests that treatment with some anti-TNF agents like Remicade and Humira can increase the risk of lymphoma and skin cancer. Nevertheless, it’s important to note that these findings do not mean you should discontinue using anti-TNF agents. These medications are highly effective for people with rheumatoid arthritis (RA) who no longer respond to traditional DMARD therapy.