SAN FRANCISCO -- Organ transplant recipients are twice as likely as the average American to get cancer, in large part because they must suppress their immune system to avoid organ rejection and that leaves them more vulnerable to infections that can cause cancer, according to a large national study.

Transplant patients have an increased risk of developing 32 types of cancer in all, especially skin cancer, Kaposi's sarcoma, non-Hodgkin's lymphoma, and cancers associated with the organ they had removed, according to the National Cancer Institute study.

It's long been known that people who get transplants have an increased risk of developing cancer, but the study published Tuesday in the Journal of the American Medical Association is the largest ever done, and the first to look at a wide variety of cancers and transplant procedures.

"We've gotten really good at preventing organ rejection, and the way we did that is taking a sledgehammer to it and slamming down the whole immune system," said Dr. Ryutaro Hirose, an associate professor of surgery and transplantation at UCSF who was not involved in the study. "The side effect is now we see patients die of other things like cancer. We're a victim of our own success."

Nearly 30,000 transplants are performed in the United States every year. Nearly 90 percent of all transplant patients survive at least the first year after surgery, and rates are much higher - approaching 99 percent - for kidney transplants, which are the most common type of procedure. Many patients are living decades after a transplant.

Hazardous effects

In large part, the improved outcome has to do with the success of antirejection medications. But those same medications can have dangerous long-term effects.

Hirose and other Bay Area transplant experts said they weren't surprised by the findings. But they hoped the new study would lead to development of treatment guidelines - such as recommendations for regular cancer screening or preventive care - for years or even decades after transplant surgery.

The study, doctors said, also underscores the need to refine the medications used for suppressing the immune system to allow physicians to target specific parts of the body to avoid rejection instead of weakening the entire system.

"We're getting better at not over-immuno-suppressing individuals," said Dr. Robert Osorio, chairman of the transplant department at California Pacific Medical Center. But the new study backs up what Osorio and his colleagues had already noticed - that even with improved antirejection drugs and procedures, transplant patients still have a much higher risk of developing cancer and other conditions that are more common in old age.

"It wasn't too long ago that we in the transplant community were just concerned about people surviving the transplant itself," Osorio said. "As they live longer, we need these kinds of studies not only to look at the risk for malignancies, but coronary artery disease, diabetes, etc."

The National Cancer Institute study looked at more than 175,000 organ transplants done between 1987 and 2008, and linked them to registries that record cancer cases. Transplant patients overall had twice the risk of getting cancer as the general population, but the risk for certain types of cancer was much higher.

High risk for cancers

Transplant patients are eight times more likely to develop non-Hodgkin's lymphoma and 14 times more likely to get skin cancer. They have a 61-fold increased risk of developing Kaposi's sarcoma, although rates of that cancer are still low.

Lung transplant recipients are six times more likely to develop lung cancer, and kidney transplant recipients also have a six-fold increase in the risk of kidney cancer. Liver cancer recipients have a 44-fold increase in the risk of liver cancer.

Sometimes, the cancer is caused by the same disease that created the need for a transplant. For example, kidney cancer and liver cancer are both common complications of kidney and liver disease, which can recur even after a transplant.

But many of the increased cancer cases can be tied to infections. Non-Hodgkin's lymphoma, Kaposi's sarcoma, many genital cancers and liver cancer are caused by viruses. Skin cancer is not known to be caused by a virus, but the immune system is responsible for killing malignant cells, and a weakened system may let those cells grow out of control.

Some cancers - including skin cancer - may also be caused by viruses that haven't yet been discovered, said Dr. Eric Engels, lead author of the National Cancer Institute study. It's also possible that the antirejection drugs themselves are toxic and cause some types of cancer.

"We don't have any evidence that the medications cause cancer, but certainly it's something we've thought about. That's an area where we need to do more work," Engels said.

Preventive steps

Organ transplantation, he said, is one of medicine's "great success stories." But it's critical that patients be made aware of their long-term risks and take whatever preventive measures they can - from screening for early cancers to quitting smoking or wearing sunscreen every day, transplant experts said.

"If you know you're going to get a transplant down the line, you might as well switch your lifestyle right away. If you have even a hint of kidney disease, you shouldn't be going out in the sun," Hirose said. "It costs a lot of money to do a transplant, and if we're going to be spending that money, we need to make sure they're not going to die of cancer five years later."

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