For the first time, direct serum measurements of the known human carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Agent Orange have been linked to the likelihood of developing MGUS (monoclonal gammopathy of undetermined significance) and myeloma. In a study published online Sept. 3 in the journal JAMA Oncology, Dr. Ola Landgren and colleagues examined stored serum samples from Vietnam War veterans involved in Operation Ranch Hand, which resulted in significant exposure to TCDD. There was a greater than two-fold increased risk of MGUS associated with higher levels of TCDD versus matched controls. The overall prevalence of MGUS was 7.1% in Operation Ranch Hand veterans versus 3.1% in comparison veterans.

The linkage of the occurrence of MGUS with blood levels of TCDD, a chemical known to cause cancer in humans, is important for several reasons. First, this begins to answer the question “What causes MGUS and/or myeloma?” The proof of principle here is that a cancer-causing chemical can be involved. In an editorial accompanying the article in JAMA, Dr. Nikhil Munshi explores possible mechanisms of chemical injury, such as p53 loss—a high-risk feature of myeloma.  Patients’ underlying susceptibility due to impaired immune response increases the likelihood that these toxic chemicals will be activated. 

There is now support for the data linking other toxic and/or cancer-causing chemicals to myeloma, including weed killers sprayed on GMO crops; various chemicals used by farmers and gardeners; toxic exposures from the 9/11 attacks in New York City; exposures to toxic chemicals in nail salons; exposures to fire retardants and solvents; incineration by products (including for example diesel and jet fuel exhausts); plus many other exposures linked to myeloma and MGUS over the years .There is strong validation to investigate all such associations more closely.

In the case of Agent Orange, it is tremendous to see Admiral Elmo Zumwalt finally vindicated. Adm. Zumwalt's son developed Hodgkin's disease after exposure to Agent Orange. The admiral was upset and was convinced that his previously very healthy son was sick because of Agent Orange. Zumwalt was able to persuade the US Dept. of Veterans Affairs to compensate exposure victims without detailed proof, which has been a blessing for so many who developed the seven types of cancer covered by this request.

The Supreme Court case against the manufacturer is also vindicated these many years later.

Although it is more than 50 years since exposures to Agent Orange, cancers are still emerging and now can be more readily compensated. Also, since TCDD and related chemicals persist for decades in the soil, there is a stronger case for clean-up measures. 

Thus, there are many implications of this blood-study analysis, which can lead to a better understanding of MGUS and myeloma, and ideas about how to prevent them in the future.

The idea of having a planet free of toxic chemicals is catching on, as evidenced by Pope Francis in his recent Encyclical. And, as I have written in the past, we must combat both the development of cancer AND global climate change by taking personal responsibility for pollution. 

Dr. Durie sincerely appreciates and reads all comments left here. However, he cannot answer specific medical questions and encourages readers to contact the trained IMF InfoLine staff instead. Specific medical questions posted here will be forwarded to the IMF InfoLine. Questions sent to the InfoLine are answered with input from Dr. Durie and/or other scientific advisors and IMWG members as appropriate, but will not be posted here. To contact the IMF InfoLine, call 800-452-CURE, toll-free in the US and Canada, or send an email to infoline@myeloma.org. InfoLine hours are 9 am to 4 pm PT. Thank you.

Comments

Unfortunately this comes as no surprise.My husband helped his dad farm and used all kinds if sprays. He told me one that they used he would spray it on and birds would come and eat and by the time he made a round the birds would be dead! It's no wonder so many farmers including my husband and other people are getting MM. If only we could do something about the Monsantos and Syngentas and all the other chemical companies in the world.

Yes - no surprise!! My husband passed away from his MM last year at the age of 66. We tried for two years for the Veterans to just help us out with our medicine bills, but they said NO because my husband was in Korea rather than Viet Nam. Despite pictures he had taken in both Korea and the Philippines - jungle and vegetation one day; planes fly over and spray something; no more jungle and vegetation! My husband also "moved empty barrels" that popped up after the hurricane near base in Biloxi, Mississippi - found more than one study about the water supply and soil around there having carcinogens! Sent all of this to Veterans more than once, and the answer was always NO! Pretty sad - for people like Nanci's husband and for mine. Thank you, Dr. Drurie - someone needs to keep on top of this.

Dear Victoria,

Thank you for your comment. YES, spraying did occur elsewhere, such as in Korea, the Philippines, Cambodia (especially controversial) and other war zones, and has not be acknowledged as it has for Vietnam—which is very frustrating for many, I know. Maybe it will take additional blood sample studies to convince regulators. In addition, exposures occurred in many other settings, such as working with the barrels when stored, or at loading or transfer. And, as I’ve mentioned, there are many other situations where veterans have been exposed to similar chemicals, such as the “burn pits” (link - http://usnews.nbcnews.com/_news/2013/01/10/16449918-this-generations-age...) in Afghanistan. It is important to work together on websites and elsewhere to make voices heard.
Sincerely,
Brian Durie

I am so glad to see you address the issue of what causes myeloma in such a clear and direct way. In the six years I've been involved in the myeloma community I have never seen this issue given much importance at all.

I just wonder if there is any estimate floating around about the length of time between exposure to a toxin and when myeloma develops? One can be smoldering for years but still is there some upper limit to how long it takes to develop the disease?

Thanks so much for discussing this and I look forward to seeing more about tracing the causes of myeloma so that others can be spared suffering.

Dear Nancy,
Thank you for your comment. You raise a very important point which is now being more fully investigated. When can chemical exposure occur, resulting in MGUS and myeloma later? Right now, it seems there is no upper on limit on the “latency period.” Researchers are now checking all the way back to childhood or even before birth (in utero) to see if such chemical insults can linger for many, many years and cause trouble. It definitely seems possible! It is already clear that the original insult can occur at age 20 or 30 years, then, easily, 10 years from MGUS to the onset of myeloma. What also seems likely is that there is a “second event” or trigger factor which converts MGUS into myeloma. This type of event has different risk factors and probabilities. So, there is clearly much work still to be done—but each new clue is helpful. I will continue to track new updates!
Thanks again,
Sincerely,
Brian Durie

Thanks Dr Durie. If we can eventually take another step toward showing MGUS does cause symptoms, then convince the VA, we will have made good progress. Thanks much.

Dear John,

Thank you for your note!

MGUS does in fact cause problems for patients which can often be well documented! Please let me know if there is a specific problem or reluctance and I will see what can be done. Obviously, MGUS IS a medical problem since it can turn into myeloma.

But, there are many problems with the MGUS condition itself. This is frequently underestimated or misunderstood. For example, one of the most serious MGUS conditions is amyloidosis, which is MGUS in which there is NOT myeloma, but the deposits of kappa or lambda can cause heart, kidney, nerve and other damage—and obviously requires treatment. There are many other examples where serious medical problems emerge.

The medical issue just needs to be careful explained and need for medical care justified. Sometimes just the use of the word “MGUS” is the problem. We use other terminology like “MGRS” (monoclonal gammopathy of renal significance). With this type of change in wording, I am sure we can help patients having coverage difficulties. There can be MGHS (heart) and MGNS (nerve), MG BCS (blood clot problems) and various other conditions—these are what are called protein deposition or binding diseases.

Hope this helps clarify and identifies a way forward. Good luck with this.
Yours sincerely,
Brian Durie

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