About 3 million Americans served in the armed forces in Vietnam and nearby areas during the 1960s and early 1970s, the time of the Vietnam War. During that time, the military used large amounts of mixtures known as defoliants, which are chemicals that cause the leaves to fall off plants. One of these defoliants was Agent Orange, and some troops (as well as civilians) were exposed to it. Many years later, questions remain about the lasting health effects of those exposures, including increases in cancer risk.
This article is a brief overview of the link between Agent Orange and cancer. This is not a complete review of all evidence – it is meant to be a brief summary. It also includes some information on benefits for which Vietnam veterans exposed to Agent Orange may be eligible.
Some background on Agent Orange
During the Vietnam War, US military forces sprayed millions of gallons of herbicides (plant-killing chemicals) on lands in Vietnam, Laos, and other nearby areas to remove forest cover, destroy crops, and clear vegetation from the perimeters of US bases. This effort, known as Operation Ranch Hand, lasted from 1962 to 1971.
Different mixes of herbicides were used, but most were mixtures of 2 chemicals that were phenoxy herbicides:
- 2,4-dichlorophenoxyacetic acid (2,4-D)
- 2,4,5-trichlorophenoxyacetic acid (2,4,5-T)
Each mixture was shipped in a chemical drum marked with an identifying colored stripe. The most widely used mixture contained equal parts 2,4-D and 2,4,5-T. Because this herbicide came in drums with orange stripes, it was called Agent Orange. Today, many people use the term “Agent Orange” to refer to all the phenoxy herbicides sprayed at the time. (Other types of herbicides were also used, including cacodylic acid and picloram.)
The 2,4,5-T in Agent Orange was contaminated with small amounts of dioxins, which were created unintentionally during the manufacturing process. Dioxins are a family of dozens of related chemicals. They can form during the making of paper and in some other industrial processes. The main dioxin in Agent Orange was 2,3,7,8-tetrachlorodibenzo-p-dioxin, or TCDD, which is one of the most toxic.
After a 1970 study found that 2,4,5-T could cause birth defects in lab animals, its use in Vietnam was stopped. A year later, all military herbicide use in Vietnam ended. During the 1970s, some veterans returning from Vietnam began to report skin rashes, cancer, psychological symptoms, birth defects in their children, and other health problems. Some veterans were concerned that Agent Orange exposure might have contributed to these problems. These concerns eventually led to a series of scientific studies, health care programs, and compensation programs directed to the exposed veterans.
A large class-action lawsuit was filed in 1979 against the herbicide manufacturers, and was settled out of court in 1984. It resulted in the Agent Orange Settlement Fund, which distributed nearly $200 million to veterans between 1988 and 1996.
Although there is now quite a bit of evidence about the health effects of Agent Orange, many questions have not yet been answered.
How were people exposed to Agent Orange?
About 3 million people served in the US military in Vietnam during the course of the war, about 1.5 million of whom served during the period of heaviest herbicide spraying from 1967 to 1969.
In studies comparing Vietnam veterans with veterans who had served at the same time elsewhere, blood TCDD (dioxin) levels were found to be higher among those who had served in Vietnam, although these levels went down slowly over time.
Exposure to Agent Orange varied a great deal. Most of the large-scale spraying in Operation Ranch Hand was done with airplanes and helicopters. However, some herbicides were sprayed from boats or trucks, and some were applied by soldiers with backpack sprayers. Those who loaded airplanes and helicopters might have been exposed the most. Members of the Army Chemical Corps, who stored and mixed herbicides and defoliated the perimeters of military bases, probably also had some of the heaviest exposures. Others with potentially heavy exposures included members of Special Forces units who defoliated remote campsites, and members of Navy river units who cleared base perimeters.
Exposures could have occurred when the chemicals were breathed in, ingested in contaminated food or drink, or absorbed through the skin. Exposure may have been possible through the eyes or through breaks in the skin, as well.
One of the challenges in assessing the health effects of Agent Orange exposure has been trying to determine how much any individual veteran was exposed to (or even what they were exposed to), as very little information of this type is available.
Does Agent Orange cause cancer?
A great deal of research has looked at whether exposure to Agent Orange might cause cancer.
What do studies show?
Researchers use 2 main types of studies to try to determine if a substance or exposure causes cancer.
- Studies in people: One type of study looks at cancer rates in different groups of people. Such a study might compare the cancer rate in a group exposed to a substance to the rate in a group not exposed to it, or compare it to the cancer rate in the general population. But sometimes it can be hard to know what the results of these studies mean, because many other factors might affect the results.
- Lab studies: In studies done in the lab, animals are exposed to a substance (often in very large doses) to see if it causes tumors or other health problems. Researchers might also expose normal human cells in a lab dish to the substance to see if it causes the types of changes that are seen in cancer cells. It’s not always clear if the results from these types of studies will apply to humans, but lab studies are a good way to find out if a substance might possibly cause cancer.
In most cases neither type of study provides conclusive evidence on its own, so researchers usually look at both human and lab-based studies when trying to figure out if something causes cancer.
Studies in people
Studies of Vietnam veterans provide some of the most direct evidence of the health effects of Agent Orange exposure.
The Centers for Disease Control and Prevention (CDC), the US Air Force, and the Department of Veterans Affairs (VA) have conducted studies in thousands of Vietnam veterans. However, most of these studies have been limited by the fairly small number of people who were highly exposed to Agent Orange. About a dozen states have also conducted studies of their veterans, and a series of studies of Australian Vietnam veterans has also provided some information on cancer risk.
Studies of 3 other groups of people have also provided important information on the potential cancer-causing properties of Agent Orange exposure:
- Vietnamese soldiers and civilians exposed to the same herbicides as United States service personnel, often for more prolonged periods (although there have been few thorough health studies in these populations)
- Workers exposed to herbicides in other settings, such as herbicide manufacturing workers, herbicide applicators, farmers, lumberjacks, and forest and soil conservationists, who often had much higher blood dioxin levels than Vietnam veterans
- People exposed to dioxins after industrial accidents in Germany, Seveso (Italy), and California, and after chronic exposures at work and in the environment
Each of these groups differs from the Vietnam veterans in the characteristics of the people exposed, the nature of the dioxin exposures, and other factors such as diet and other chemical exposures.
Taken together, these studies have looked at possible links between Agent Orange (or dioxin) and a number of cancer types.
Soft tissue sarcoma: Most studies in Vietnam veterans have not found an increase in soft tissue sarcomas. However, soft tissue sarcomas have been linked to phenoxy herbicide exposure in a series of studies in Sweden and in some studies of industrially exposed workers. Many studies of farmers and agricultural workers show an increase in soft tissue sarcomas, which may be related to herbicide exposure. Soft tissue sarcomas have also been linked to dioxin exposure in some chemical manufacturing workers and in some other workplace studies.
Non-Hodgkin lymphoma: Most studies of Vietnam veterans have not shown an increase in non-Hodgkin lymphoma (NHL). But several studies have found a link between phenoxy herbicide exposure (usually at work) and NHL. Some studies of farmers and agricultural workers also suggest this association, although not all studies have found such a link.
Hodgkin lymphoma (Hodgkin disease): Most studies of Vietnam veterans have not found an increase in Hodgkin lymphoma. However, it has been linked to phenoxy herbicide exposure in some other studies. Many studies of farmers and agricultural workers show an increase in Hodgkin lymphoma, which may be related to herbicide exposure.
The link between Hodgkin lymphoma and dioxin exposure specifically is less clear, as studies have had mixed results.
Lung and other respiratory cancers: Most studies of Vietnam veterans have not shown an increase in respiratory cancers, such as those of the lung, trachea (windpipe), and larynx (voice box). Most studies of people exposed to herbicides at work, such as herbicide manufacturing workers, herbicide applicators, and farmers have not found an excess risk of lung cancer.
Most studies of groups of people highly exposed to dioxin after industrial accidents have not found an increase in respiratory cancers. However, chronic exposures to high levels of dioxin in the workplace have been linked with increased risk of respiratory cancers in some studies.
Prostate cancer: Most studies of Vietnam veterans have not found an excess risk of prostate cancer, but results from a few studies have suggested a possible link. For example, a recent study in veterans found that exposure to Agent Orange was linked to an increased risk of developing more aggressive forms of prostate cancer.
Studies of other groups have also yielded mixed results. Most studies of people exposed to phenoxy herbicides at work do not show an excess of prostate cancer. However, some studies have found a small excess risk of prostate cancer related to dioxin exposure.
Multiple myeloma: Most studies of Vietnam veterans have had too few cases of multiple myeloma (a type of immune system cancer that affects the bones) to be helpful in determining if there is a risk. However, at least one study has found that exposed veterans have an increased risk of monoclonal gammopathy of undetermined significance (MGUS), which can be a precursor of multiple myeloma.
Other studies of people exposed to pesticides, herbicides, and/or dioxins have suggested a possible link to multiple myeloma as well. Several studies of farmers and agricultural workers have reported a small increase in risk of multiple myeloma, although some studies show no excess risk.
Bladder cancer: There have only been a handful of studies looking at bladder cancer risk in Vietnam veterans, and the results have been mixed. Results have also been mixed in studies of people exposed to herbicides at work or from industrial accidents.
Gastrointestinal (GI) cancer: Cancers of the GI system – esophagus, stomach, liver, pancreas, colon, and rectum – have been extensively studied in Vietnam veterans, groups with herbicide exposure in the workplace, and people exposed to dioxins. Most of these studies have not found a link between these exposures and any GI cancer.
Brain tumors: Most studies have not found a link between brain tumors and Vietnam service, workplace herbicide exposure, or dioxin exposure.
Breast cancer: As most Vietnam veterans are men, in whom breast cancer is very rare, few studies have looked for possible links between Agent Orange and breast cancer. Some studies looking at exposure to dioxin in the workplace or from industrial accidents have noted a possible link, but others have not, so more research is needed in this area.
Other cancers: Few studies have looked at a possible link between Agent Orange exposure and other cancers, including cancers of the nose and nasopharynx (upper part of the throat), cervix, endometrium (uterus), ovaries, liver and bile ducts, bone, kidneys, testicles, or skin, or leukemias other than chronic lymphocytic leukemia (in veterans themselves, as opposed to their children).
Leukemia and other cancers in the children of veterans: A few studies have pointed to a possible link between a father’s exposure to Agent Orange or other herbicides and leukemia in his children. But several other studies have not found links with leukemia or other childhood cancers.
Studies done in the lab
Herbicides such as 2,4,5-T and 2,4-D are not considered highly toxic compounds by themselves, and high doses are needed to cause effects in lab animals. These compounds have not been linked with cancer in animal studies.
In the lab, TCDD (dioxin) increases the risk of a wide variety of tumors in rats, mice, and hamsters. In lab dish studies, it has been shown to alter which genes inside cells are turned on or off and to affect how cells divide and die, all of which could affect cancer risk.
What the expert agencies say
Several national and international agencies study substances in the environment to determine if they can cause cancer. (A substance that causes cancer or helps cancer grow is called a carcinogen.) The American Cancer Society looks to these organizations to evaluate the risks based on evidence from laboratory, animal, and human research studies.
Some of these expert agencies have looked at whether Agent Orange or related compounds can cause cancer.
Institute of Medicine
Starting in the early 1990s, the federal government directed the Institute of Medicine (IOM), now known as the Health and Medicine Division of the National Academies, to issue reports every 2 years on the health effects of Agent Orange and similar herbicides. First published in 1994 and titled Veterans and Agent Orange, the IOM reports assess the risk of both cancer and non-cancer health effects. Each health effect is categorized as having one of the following:
- Sufficient evidence of an association
- Limited/suggestive evidence of an association
- Inadequate/insufficient evidence to determine whether an association exists
- Limited/suggestive evidence of no association
This framework provides a basis for government policy decisions in the face of uncertainty.