Organ Transplants, the Immune System and Cancer

People who receive organ transplants have long been known to have substantially elevated risks of cancer, especially lymphoma. This is due to the grueling immunosuppressive drug regimens they must undergo, and the possibility that these regimens reactivate latent infections with viruses known to cause malignancies. In this way, transplant patients present a special opportunity to learn about the roles of the immune system and infections in causing cancer in all persons. However, early studies of cancer after transplants were limited by small numbers of patients and difficulties in calculating the baseline cancer risks that the patients would have had, unrelated to receiving a transplant. In recent work, these methodologic problems were solved through the innovative approach of linking together registries of transplant recipients with population-based cancer registries, like the Greater Bay Area Cancer Registry operated by CPIC.

Christina ClarkeIn the last three years, CPIC Research Scientist Christina Clarke, Ph.D., M.P.H., has represented the state of California in a large, national collaborative effort led by the National Cancer Institute (NCI) to link together the US National Scientific Registry of Transplant Recipients with cancer registries from 14 states. This bureaucratically complex effort—called the Transplant Cancer Match—has now paid off by yielding the world’s largest database of cancer among transplant patients. With information about cancer in 175,732 solid organ transplant patients (58% kidney, 22% liver, 10% heart, and 4% lung), this powerful new research resource offers much greater numbers and a wider variety of types of organ transplants than ever available before.

Our first research results from this landmark effort were published in the prestigious medical journal JAMA on November 2, 2011. In this paper, we report that overall, transplant patients were more than twice as likely as healthy individuals to develop any kind of cancer. We found that risk was increased for 32 different malignancies, some known to be caused by latent infections (like anal cancer (human papilloma virus (HPV)) and Kaposi sarcoma (HHV8)) and others not believed to be caused by viruses (melanoma, thyroid, and lip cancers). We confirmed that transplant patients were almost eight times as likely to develop non-Hodgkin lymphomas as healthy people, speaking to a major role of immune suppression in the cause of this collection of white blood cell cancers. Interestingly, risks of developing certain cancers (lung, liver, and kidney) in persons receiving transplants of those organs seemed to be related to higher risks of cancer in the transplanted organ itself, which may speak to an important role of host immune activity in tissue that becomes cancerous.
Dr. Clarke and Senior Research Scientist Sally Glaser, Ph.D., are leading ongoing studies to delve more deeply into how the risks of specific non-Hodgkin and Hodgkin lymphomas are increased in transplant patients. The hope is that these studies, based on such a large and powerful database, will provide further enlightenment about immune suppression and infection as causes of these particular cancers.

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