Agent Orange Linked to Increased Risk of MGUS in Some Vietnam Veterans

By Miriam Falco,

Thursday, October 15, 2015


US Air Force veterans who participated in the spraying missions of Agent Orange during the Vietnam War have a more than twofold increased risk of developing a condition called monoclonal gammopathy of undetermined significance, or MGUS, a precursor to multiple myeloma. An association between Agent Orange and multiple myeloma has been suspected based on other studies involving farmers and agriculture workers, but this study provides the first direct evidence linking Vietnam veterans exposed to Agent Orange with MGUS.

  • During the Vietnam War, the US Air Force sprayed more than 11 million gallons of the herbicide Agent Orange over Vietnam.
  • Agent Orange contains TCDD, which is classified as a human carcinogen.
  • Veterans who participated in the spraying were found to have a more than twofold increased risk of developing MGUS.
  • Not everyone with MGUS gets multiple myeloma, but everyone with multiple myeloma has MGUS first.
  • A simple blood test is available to detect MGUS.

Fifty years after the US Air Force began spraying Agent Orange in Vietnam, new research shows that veterans exposed to the herbicide are more than twice as likely to develop monoclonal gammopathy of undetermined significance (MGUS), a precursor to multiple myeloma.

A team of researchers led by Ola Landgren, Chief of Memorial Sloan Kettering’s Myeloma Service, analyzed serum samples from 459 US Air Force personnel involved in aerial herbicide spray missions during the Vietnam War, as well as 459 samples from veterans who served there at the same time but were uninvolved in the spraying missions.

Plane spraying Agent Orange over a forest.

All of these veterans served between 1962 and 1971, when the US military dropped more than 19 million gallons of herbicides in Southeast Asia during Operation Ranch Hand.

Researchers tested for the presence of MGUS and also concentrations of TCDD, a contaminant of Agent Orange that’s been classified as a human carcinogen since 1997.

They found 7.1 percent of Ranch Hand veterans had MGUS, a precursor of multiple myeloma, compared with only 3.1 percent of the comparison group, says Dr. Landgren — a more than twofold higher risk. The risk of getting MGUS was significantly higher among veterans younger than 70 years of age.

The researchers also found that those vets who developed MGUS had higher TCDD levels in their blood samples.

 “This provides the first direct scientific evidence that there is a link between Agent Orange and the development of multiple myeloma [in Ranch Hand participants],” Dr. Landgren explains.

The findings were published in JAMA Oncology on September 3.

Wide Use and Exposure

Agent Orange was the most widely used herbicide combination sprayed during the Vietnam War, according to a 2003 Department of Veterans Affairs report. Most adverse events linked to it are blamed on TCDD.

The herbicide was used to protect US troops on the ground by stripping the forests, thereby depriving enemy soldiers of protective foliage. Agent Orange was first used in 1965, according to a 2003 Department of Veterans Affairs report. More than 11 million gallons of the chemical were used as tactical herbicides.

Dr. Landgren advises Vietnam veterans to get a simple blood test to identify MGUS. Research shows that early detection of MGUS results in better outcomes for those who do develop multiple myeloma.

An association doesn’t necessarily mean causation. But, as Nikhil Munshi, a multiple myeloma expert at Harvard School of Medicine, explained in an accompanying editorial:

“Although this study associated risk of MGUS with [Agent Orange] exposure, the fact that all [multiple myeloma] cases originate from MGUS provides the first scientific evidence for a direct link between multiple myeloma and Agent Orange exposure.”

This new research was made possible by previous work Dr. Landgren led at the National Cancer Institute before coming to MSK. He and his colleagues studied data from more than 77,000 participants in the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial, who were cancer-free at the start of the study. Seventy-one participants developed multiple myeloma during the study. Dr. Landgren and his team found that “virtually all multiple myeloma cases were preceded by MGUS.”

Previous studies showed an association between pesticide exposure and an increased risk of MGUS and multiple myeloma, but “no studies [had previously] uncovered such an association in Vietnam War veterans,” according to the JAMA Oncology study.

There are real clinical implications to be drawn, Dr. Landgren says, and a very specific group of people can and should be screened for MGUS. Even though not everyone with this precursor condition goes on to develop cancer, his work shows that everyone who has multiple myeloma had MGUS first. Prior work by Dr. Landgren and others shows that the risk of transformation from MGUS to multiple myeloma is about 1 percent per year; for example, 30 years of follow-up equals a 30 percent cumulative risk.

Dr. Landgren emphasizes the value of early detection and suggests that Vietnam veterans get a simple blood test to identify MGUS. That’s because another recent study by Dr. Landgren and co-workers, also published in JAMA Oncology, shows that patients with MGUS who develop multiple myeloma during clinical monitoring have a 10 to 15 percent better overall survival and experience fewer complications than those with multiple myeloma who never received an MGUS diagnosis.


Do you know anything about Agent Blue and the arsenic in it relating to Bladder Cancer. Are there any studies or any information??? The VA is not helpful.

Thank you for your comment. For this particular question about a possible link to bladder cancer, we suggest you contact the National Cancer Institute’s Cancer Information Service at 800­4CANCER (800­422­6237). To learn more about the CIS, including Live Chat help and how to send them an email message, go to

I was diagnosed with MGUS at MSKCC 11 years ago. I see a local hemotologist/oncologist once a year and my M proteins have remained stable throughout. The area where I lived for many years, Commack LI, swarmed with termites. All homes in the neighborhood were extensively treated on a repeat basis until the pesticide was banned. Many neighbors developed cancers of different kinds, too many to say it was law of averages, including my husband and two of my dogs. Can exposure to the pesticide be the cause of the MGUS as well as other cancers?

Thanks for your question! We reached out to Dr. Landgren, who can't comment on the details of this particular case, but mentions that he and coworkers published a study in 2009 that linked pesticide exposure to risk of MGUS. The study was done in men who routinely work with pesticides (including insecticides) as part of their jobs. The risk of developing MGUS was 2 times greater among those men.

Lymphoma is another disease that's been linked to exposure to fertilizers, pesticides, etc. More here:

If you'd like to learn more about carcinogens, a good place to ask is the National Cancer Institute. They have a hotline as well as an online chat available. Here are their contact details:

Thank you again for your question, and we wish you all the best.

My husband was treated for two different cancers at MKSCC: Prostate & Kidney.
Unfortunately, he died last year, but perhaps his medical records at Sloan mught shead some light?
Also, what about the offspring of these veterans?

We are very sorry for your loss. If you'd like to learn more about how this research might apply to your husband's case, we recommend you discuss it with his healthcare team. You might also be able to get information from the National Cancer Institute's Cancer Information Service at 800-4CANCER. Thank you for your comment.

I was in Vietnam 1964-1967 onboard ship and on ground during the agent orange spraying. Please direct me to a MGUS physician.

Thank you for reaching out. We recommend you consult with your personal physician about being tested and monitored for MGUS.

If you would like to make an appointment with a Memorial Sloan Kettering physician, please call our Physician Referral Service at
800-525-2225 or go to­care/appointment. Thanks for your comment.

You also can learn more about MGUS here:…

I have been diagnosed with MGUS. I am 68 years old. I was on the ground in the boondocks of Vietnam in 1968 and part of 1969. A few years prior, I worked for the Division of Forestry in California. One of my duties was spraying DDT as part of a pine tree beatle program.

I was in the boondocks of Vietnam in 1968 and part of 1969. A few years prior, I was part of a team with the Div. of Forestry in California, that sprayed a mixture of DDT and Diesel on dead pine trees as a Beatle remediation program. I was diagnosed with MGUS last year. I am 68 years old.

My husband is 78 and was diagnosed with Smoldering Multiple Myeloma 2 years ago. He was in the Air Force from 1955-1959.

I know this was prior to the Vietnam Agent Orange use (1965), but could it or its predecessor have been used earlier?

Alice, we're sorry to hear about your husband's diagnosis. This is something he should discuss with the US Department of Veterans Affairs. If he is being treated at a VA hospital, his doctors there may have some information on this. Thank you for your comment.

Hello, I am the daughter of a Vietnam veteran. My father had excessive Agent Orange exposure. He still has skin irritations to this day from it. I've heard stories where he had it dripping off of him. I am 44 years old and was diagnosed with MGUS approximately five years ago. Unfortunately, it may be in the smoldering myeloma stage now. There is not a family history of myeloma. I have heard there is a correlation of a parent's exposure to Agent Orange and their children having a higher risk of MGUS/SMM/MM. Do you have any further information on this? I come from a family with fairly good genes, and my brother and I have had different medical issues that started rather young (e.g., Hypothyroidism, pre-cancerous breast lump, GERD, etc. in our 20's and early 30's). We both take good care of ourselves and always have. It's puzzling why we seem to have more ailments than other people our age. As a side note, my dad also has a lot of medical issues at this point in his life (he is 68) and his other family members do/did not. He is currently under VA care. Any information you may have would be appreciated. Thank you.

Janine, we forwarded your comment to Dr. Landgren, who replied, "No study has assessed the question whether there is a link between Agent Orange exposure and risk of MGUS/SMM/MM among their children. When it comes to familial aggregation patterns of these disease, there are Scandinavian studies assessing the risk of MGUS/myeloma among family members of individuals with MGUS or myeloma. Those Scandinavian studies show there is a 2-fold higher risk of MGUS/myeloma among family members of MGUS/myeloma patients. Be careful when interpreting these data; the risk of myeloma is about 5 per 100,000 person-years in the general population; therefore the 2-fold increased risk among family members translates into a very low ABSOLUTE RISK (about 10 per 100,000 person-years). Also the mechanisms behind these observations are unclear; it may be genetic, environmental, or a combination." Thank you for your comment.

I have MM/amyloidosis.I worked at a gas utility company in the street dept. for 36 years.I was exposed to blowing gas,dust particles from steel and cast iron pipes,also dust from jack hammering concrete and asphalt pavement,etc. also exposed to oils and paint fumes from pipe coatings.I wonder if these things contributed to my illness.

Hi Phil, we forwarded your comment to Dr. Landgren, who responded, "It is not possible to answer your question in detail based on the information you provide; also it takes special experts in the field of environmental and occupational exposures. To my knowledge, when assessing individual cases, these experts typically work together with legal firms that are specialized on this topic. If you intend to pursue these questions further, you may want to seek contact with such experts/legal firms." Thank you for your comment.

If you have MGUS And then develop Multiple Myeloma. What treatment would you recommend?

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