02. PTC Risks by Organ Type Introduction
updated: 11/16/2020 Note: we welcome your comments/suggestions via e-mail to GleasonJim@TRIOweb.org
Imagine this too common scenario:
A candidate for organ transplant attends the pre-transplant introduction offered by most transplant programs. Among the overwhelming amount of information explained is the fact that a transplant recipient will be on immunosuppressant medications for the rest of their lives and with that comes a higher risk for cancers. With a focus on the transplant process, this is of little note at the time. After the transplant again there is mention of that higher risk for cancer, but with all the other important things that seem of little consequence, especially since those cancers typically do not arise until years later. Especially for kidney recipients, due to the high volume of transplants at most programs, a patient often transitions back to their local nephrologist after that first-year post-transplant. Now they are under the care of a kidney doctor who is not a transplant specialist and thus may get little attention to that increased risk for cancers as the years go on.
How much higher is that risk for a transplant recipient? See more detail in the Overview below these videos.
Watch this introductory video to better understand the post-transplant cancer risk in general, then follow on to your specific type of organ transplant to see what cancers are more common for that type of transplant.
Many studies now confirm that cancer is a major source of morbidity and mortality following solid organ transplantation and has become one of the three major causes of death after transplantation in the past decade. A recent study supports this issue further. From The Oncology Report: Squamous cell carcinoma (SCC) is the most common cancer to occur after organ transplantation,” Dr. Chestnut and his associates noted. “The malignancy is 65-250 times more common, is more than 4 times more likely to metastasize, and has a mortality rate of 5% compared with a rate of less than 1% in immunocompetent patients.” Thus, knowledge of post-transplant cancer risks and options for prevention are critically important to all transplant recipients.
People who have had solid organ transplants (lung, heart, liver, kidney) have a higher risk of developing cancer. This is most often due to immunosuppressive medications used to prevent rejection, as well as infection with viruses known to cause cancer (HPV, Epstein Barr, H. Pylori). The risk of different cancers varies depending on the organ transplanted, which immunosuppressive medications and what doses were used and other risk factors the patient may also have.
The cancers that occur at higher rates in transplant recipients include:
- Non-melanoma skin cancers (squamous cell and basal cell)
- Non-Hodgkin lymphoma or Post-transplant lymphoproliferative disorders (PTLD)
- Kaposi sarcoma
- Cancers of the anogenital area (anus, vulva, penis)
- Head & neck cancers (lip, oral, tonsil are most common)
- Kidney cancer
- Lung cancer
- Hodgkin lymphoma
- Thyroid cancer
- Stomach cancer
- Liver cancer
- Colorectal cancer
- Source: https://www.oncolink.org/risk-and-prevention/medications-health-history-and-cancer-risk/solid-organ-transplant-and-cancer-risk
Root causes of post-transplant cancers
So you wonder why the cancer risks are different by type of organ transplant? Since most of the higher risk is due to our immunosuppressant medications, one can understand that with different medications and different dosages used for each type of organ transplant, those risks would vary by organ type.
In the topics that follow, cancer risk differences are described by each type of transplanted organ, so read on for your specific organ topic . . .You heard Dr. Tsai describe the 'root causes" of cancer post-transplant in his video above, but medication was just the main contributing factor. There are many others based on such things as certain medications making the patient more sensitive to sunlight, for example, along with age, gene and DNA differences, family and individual life histories, to name just a few more.
Why does risk increase?
- A popular notion among recipients is that "cancer comes packaged with the transplanted organ." While this is possible, it is not the most common reason for someone to develop cancer after receiving a kidney transplant. Here are some more likely explanations:
- Immunosuppressive therapy: As you might know, getting a kidney transplant entails being on medications to suppress your immune system. Usually, these medications need to be continued indefinitely. Certain kinds of medications used for this purpose after the transplantation might increase your risk more than others. For instance, immunosuppressant medications which target certain kinds of white blood cells (e.g. OKT3 or antilymphocyte serum) will significantly increase the risk of something called "post-transplant lymphoproliferative disorder" or PTLD. However, more frequently, it is the overall extent/level of immunosuppression induced by being on multiple different immune suppression medications, rather than the quality of one specific drug, which increases cancer risk.
- An easier way to understand this concept is to realize that cancer cells are constantly being produced in our bodies, in general. The reason we don't develop a new malignancy every day is that these "lone-wolf" cancer cells are identified by our immune system surveillance and destroyed at the very outset. Therefore, our immune system is not just a protective mechanism against infections, it is also a protective mechanism against aberrant cell production (which could later turn into cancer). Suppressing this very immune system will, therefore, increase cancer risk.
- Infections: Certain viral infections specifically increase the risk of cancers. Kidney transplant recipients face a greater risk of viral infection because of an immunosuppressed status. Viruses multiply by taking over and tinkering with our cells' replication machinery (the DNA in some cases). This may be one possible explanation for why viral infection increases cancer risk. Examples of these viruses include the Epstein-Barr virus (which increases the risk of lymphoma), the Human Herpes Virus-8 (associated with Kaposi sarcoma), and Human Papilloma Virus (associated with skin cancers).
- Source: https://www.verywellhealth.com/link-between-kidney-transplants-and-cancer-4125901
- The reasons for the increased risk of cancer after transplantation are various and probably include an interplay of transplant-related factors such as the types, duration, and burden of immunosuppression both before and after transplantation, exposure to specific viral infections, time on dialysis prior to transplantation, and traditional risk factors such as sun exposure, smoking, and age.
- After a transplant, the recipient must take powerful immune system-suppressing medications to prevent the new organ from being rejected. But those medications put transplant recipients in a catch-22 situation, said Dr. Darla Granger, director of the pancreatic transplantation program at St. John Hospital and Medical Center in Detroit. "Suppressing the immune system does increase the risk of cancer. And, if you have cancer, you want a strong immune system to fight cancer," she added. Another issue with the immunosuppressants is cancers that are related to viruses. For example, non-Hodgkin and Hodgkin lymphomas are linked to the Epstein-Barr virus, while cervical and several other types of cancers are caused by the human papillomavirus, and some liver cancers are caused by hepatitis B or C viruses. "We've always known that certain tumors are increased after transplantation. Certain tumors are known to be related to viruses, so when we give immunosuppressant drugs, we're decreasing the body's ability to fight off viruses," explained Dr. Lewis Teperman, chief of transplant surgery at NYU Langone Medical Center in New York City. Not all of the cancers can be linked to immunosuppression, however. In some cases, especially with liver and lung cancers, it's possible that a tiny cancer was present in the body before transplant.
- WHY IS CANCER A PROBLEM AFTER TRANSPLANTATION? A third (one in three) of all people in the UK develop cancer, even if they are otherwise completely well. In the US, 1 in 2 women and 1 in 3 men will develop cancer in their lifetime, so it is not surprising that cancer is a problem in transplant patients. However, cancer is more common in transplant patients than in the general population. A research study has shown that 25% of patients who live for 20 years after a transplant develop some type of cancer. This is because the body’s immune system (natural defense) not only fights off invaders into the body such as germs but tries to prevent cancer. Suppression of the immune system after a kidney transplant can allow cancer to develop. (burden of immunosuppression, rather than a particular drug). Having said that, most types of cancer are only slightly more common for transplant recipients than in the general population. However, there are three types of cancer that are caused by viruses and are a particular problem after kidney transplantation. These are skin cancers, lymphoma and cervical (neck of the womb) cancer in women.
Step 1: Read the "Cancer Risk by Organ Type" topic for your organ of interest (see organ type icon links below) and understand the higher risks of specific types of cancer post-transplant common to your organ transplant type.
Step 2: . . . then under LINKS on this PTC site, see the "10 Best Practices" for steps to take to control and deal with your personal PTC risk. Make these your life-extending habits.