8 Types of Cancer Linked to Rheumatoid Arthritis

If you have rheumatoid arthritis (RA), you may be at increased risk for certain cancers because of RA medications—or RA-related inflammation itself.

The best thing you can do is to be aware, but don't worry excessively. "The risk of all of these is very, very low," says Stanley Cohen, MD, clinical professor of internal medicine at the University of Texas Southwestern Medical School and co-director of the division of rheumatology at Presbyterian Hospital, in Dallas. "When you look at the numbers, the relative risk is higher but the actual risk is low."

RA has even been linked to a lower risk of some types of cancer.

RA has been linked to lung-cancer risk, possibly because smoking increases the chances of getting RA in the first place. Research suggests, however, that even nonsmokers with RA have a slightly higher risk of getting lung cancer.

"In the absence of smoking, the numbers are really small," says Marc Hochberg, MD, MPH, professor of medicine and head of rheumatology and clinical immunology at the University of Maryland Medical Center, in Baltimore. "But there is a higher risk due to inflammation and scarring in the lungs from RA."

If you smoke, quit. RA patients with lung disease should avoid taking methotrexate or leflunomide because they may worsen lung damage, Dr. Hochberg says.

Research suggests that melanoma, the most dangerous type of skin cancer, is more likely in people who take TNF inhibitors, possibly because these drugs suppress the immune system.

A 2007 study found that people with RA who take TNF inhibitors have more than double the risk of melanoma as RA patients who do not, although the actual risk was low (32 out of nearly 14,000 RA patients developed melanoma).

People with RA also appear to be at higher risk of developing more treatable types of non-melanoma skin cancer. A 2011 analysis found that people taking TNF inhibitors had a 45% greater chance of developing non-melanoma skin cancer. (The authors of both studies received money from pharmaceutical companies that make RA drugs.)

Multiple myeloma is a relatively rare form of cancer that affects white blood cells called plasma cells; about 20,000 new cases will be diagnosed in 2011, according to the American Cancer Society.

People with RA seem to have a 17% higher chance of getting the disease, according to a 2008 study. Dr. Hochberg says people who have RA for long periods of time may produce excess antibody-related proteins in the blood, a condition called hyperglobulinemia. This can sometimes develop into multiple myeloma, a disease characterized by the abnormal production of plasma cells.

On the other hand, some studies suggest that multiple myeloma could lead to RA.

More than any other malignancy, RA seems to increase the risk of non-Hodgkin's lymphoma and Hodgkin's disease, cancers of immune cells called lymphocytes.A 2003 study of more than 76,000 Swedish RA patients found they had a two- and three-times higher risk of non-Hodgkin's lymphoma and Hodgkin's disease, respectively, than people without RA. (Of the patients, 458 and 77 developed non-Hodgkin's lymphoma and Hodgkin's disease, respectively, over a 35-year period.) Moreover, a 2006 study found that those with the most severe RA symptoms are at the highest risk of lymphoma.

Dr. Hochberg says this may be due to chronic stimulation of the immune system, which occurs in patients who have had long-term moderate to severe arthritis that is not well controlled.

There have been two cases of RA patients developing a rare and fatal type of non-Hodgkin's lymphoma called hepatosplenic T-cell lymphoma while taking Humira (adalimumab), a TNF inhibitor.

The FDA also

reported 40 other cases in patients (mostly adolescents) with Crohn's disease and ulcerative colitis who were taking Humira, as well as other TNF inhibitors and immunosuppressants—all of which are also prescribed for RA. Although the agency says it is difficult to know the risk of these drugs because the conditions on their own are associated with increased lymphoma risk, it says the risks and benefits should be "carefully weighed when prescribing these drugs to children and young adults."

Data is mixed on the link between RA and leukemia. A Finnish study of almost 12,000 men and 35,000 women found higher rates of leukemia among men with RA compared to those without it, but there was not a significant increase among women with RA.

Dr. Hochberg says the link between leukemia and RA is rare and is a complication associated with immunosuppressive therapies like Cytoxan (cyclophosphamide) and Azasan (azathioprine), which are used to treat severe RA. Methotrexate has also been associated with increased incidence of leukemia. Dr. Hochberg is a paid consultant for several companies that make RA medicines, including Bristol-Myers Squibb, which makes Cytoxan.

People with RA appear to have a slight advantage when it comes to breast and colorectal cancers; their risk is a bit lower than people without RA.

A 2008 research analysis estimated that people with RA had a 16% and 23% lower chance of developing breast and colorectal cancers, respectively. (Bristol-Myers Squibb, a maker of RA medicines, funded the study.)

Dr. Hochberg says it is not known exactly why this happens, but it may be because many RA patients frequently take nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen, which curb inflammation. This may lower the risk of these cancers.

Long-term usage of NSAIDs may also reduce the risk of death in men with RA who develop prostate cancer.

A study of nearly 100,000 Swedish prostate-cancer patients presented at a 2008 meeting of the American Society of Clinical Oncology found a 12% reduced risk of death among men with RA compared to those without. Men who had been hospitalized for RA treatment six or more times (thus more likely to be taking NSAIDs) had the lowest mortality rates.