Agent Orange and Cancer – pro

Agent Orange and Cancer

About 3 million Americans served in the armed forces in Vietnam 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 were chemicals that caused the leaves to fall off plants. One of these defoliants was Agent Orange, and some troops were exposed to it. Many years after US forces withdrew from Vietnam, questions still remain about the lasting health effects of those exposures, including increases in cancer risk. In studies that compared Vietnam veterans with veterans who had served at the same time elsewhere, TCDD (dioxin) levels were found to be elevated among those who had served in Vietnam, although the elevations diminished slowly over time.

After a scientific report in 1970 indicated that 2,4,5-T could cause birth defects in lab animals, the use of 2,4,5-T in Vietnam was suspended. A year later, all military herbicide use in Vietnam ended. During the 1970s, veterans returning from Vietnam began to report skin rashes, cancer, psychological symptoms, birth defects and handicaps in their children, and other health problems. Some veterans were concerned that Agent Orange exposure might have contributed to these health problems. These concerns helped initiate a series of scientific studies, health care programs, and compensation programs directed to the exposed veterans.

As the US veteran population ages, study results continue to emerge. This agent certainly ahs been shown to have mutagenic and cancerogenic properies. The question of causality has been extensively litigated. 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. Bccause the case has been setteld, there has not been a legal finding of causality.

Studies of Vietnam veterans potentially provide the most direct evidence of the health effects of Agent Orange exposure. However, because of the small number of highly exposed persons, these studies have yielded very limited information on cancer.

The Vietnam Experience Study (VES), conducted by the Centers for Disease Control (CDC), was a study that compared about 9,000 Vietnam Army veterans with about 9,000 Vietnam-era Army veterans who served elsewhere. A related effort was the CDC Selected Cancers Study, a study conducted in 8 cancer registries that provided data on non-Hodgkin lymphoma, sarcomas, and other cancers. In both of these studies, the number of veterans with heavy exposure to Agent Orange was too small to draw firm conclusions.

The Department of Veterans Affairs, formerly the Veterans Administration (VA), also conducted a series of studies beginning in the 1980s. The VA studies ranged from large-scale studies to studies of specific subgroups of veterans.

Both the CDC and the VA studies looked broadly at Vietnam veterans, without a special focus on Agent Orange exposure (although some VA studies focused on Chemical Corps veterans).

In contrast, the Air Force Health Study specifically compared about 1,200 Ranch Hand veterans directly involved in herbicide distribution to 1,300 veterans not involved. This 20-year study, launched in 1982, involved periodic physical exams, medical records reviews, and blood dioxin measurements. Although this study focused more directly on Agent Orange exposure, the relatively small number of subjects, and the even smaller number with elevated blood dioxin levels, greatly limited the study’s power to detect increases in cancer incidence.

At the state level, about a dozen states, mostly in the Midwest and Northeast, have conducted studies of their veterans, some of which have yielded cancer information.

Finally, a series of studies of Australian Vietnam veterans has provided information on cancer risk. These studies, too, were limited by their small size, by the lack of detailed exposure assessment, and (at least initially) by the relatively young age of the veterans. As the veterans continue to age, additional research should yield more information about cancer risk.

Because of the limits of the Vietnam veteran studies, studies of 3 other groups have 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 systematic 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 serum 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 populations 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.

Several national agencies have made public their conclusions and their interpetation of the evidence.
The “Agent Orange Act of 1991″ directed the Secretary of Veterans Affairs to request the National Academy of Sciences (NAS) to review and evaluate the effects of Agent Orange exposure. The Institute of Medicine (IOM), part of the NAS, responded by forming the Committee to Review the Health Effects in Vietnam Veterans of Exposure to Herbicides. The Committee has issued a series of studies, beginning with its 1994 Veterans and Agent Orange: Health Effects of Herbicides Used in Vietnam.

“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. As of the most recent update, the links between Agent Orange exposure and cancer were designated as shown. (Note that this table shows only cancers.)


Institute of Medicine: Associations Between Agent Orange and Cancer

Sufficient evidence of an association
Soft tissue sarcoma
Non-Hodgkin lymphoma (NHL)
Hodgkin disease
Chronic lymphocytic leukemia (CLL)


Limited/suggestive evidence of an association
Respiratory cancers (lung, trachea, bronchus, larynx)
Prostate cancer
Multiple myeloma

Inadequate/insufficient evidence to determine whether an association exists
Liver and bile duct cancers
Nasal/nasopharyngeal cancer
Bone cancer
Breast cancer
Female reproductive cancers (cervical, uterine, ovarian)
Urinary bladder cancer
Kidney cancer
Testicular cancer
Leukemia (other than CLL)
Skin cancers
Acute myelogenous leukemia (AML) in the children of veterans

Limited/suggestive evidence of no association
Gastrointestinal cancers (stomach, pancreas, colon, rectum)
Brain tumors

National Toxicology Program


The US National Toxicology Program (NTP), formed from parts of several government agencies, evaluates exposures that may be carcinogenic (cancer-causing). Those exposures thought to be carcinogenic are included in the “Report on Carcinogens,” published every 2 years. Each exposure is assigned to 1 of 2 categories: “known to be a human carcinogen” “reasonably anticipated to be a human carcinogen”

The first category includes substances for which human studies provide “sufficient evidence” of cancer causation in humans. The second category includes substances for which there is limited evidence of cancer causation in humans and/or sufficient evidence of cancer causation in experimental animals.

The National Toxicology Program has not listed the phenoxy herbicides, including Agent Orange, as carcinogens, but 2,3,7,8-TCDD (dioxin) is classified as “known to be a human carcinogen.”

International Agency for Research on Cancer

The International Agency for Research on Cancer (IARC) also evaluates exposures that may be carcinogenic. IARC classifies exposures into 1 of 4 categories:

Group 1 exposures are those “known to be carcinogenic to humans,” usually based on “sufficient” human evidence, but sometimes based on “sufficient” evidence in experimental animals and “strong” human evidence.

Group 2 exposures are divided into 2 categories. Group 2A (“probably carcinogenic to humans”) has stronger evidence, and Group 2B (“possibly carcinogenic to humans”) has weaker evidence.

Group 3 exposures are not considered classifiable, because available evidence is limited or inadequate.

Group 4 exposures are “probably not carcinogenic to humans” based on evidence suggesting lack of carcinogenicity in humans and in experimental animals.
IARC has not rated Agent Orange per se, but the phenoxy herbicides, including 2,4-D and 2,4,5-T, are categorized as “possibly carcinogenic to humans” (Group 2B), and 2,3,7,8-TCDD (dioxin) is categorized as “known to be carcinogenic to humans” (Group 1).

Environmental Protection Agency

The US Environmental Protection Agency (EPA) uses a classification scheme very similar to that of IARC. It classifies exposures into 1 of 5 categories:

human carcinogen
probable human carcinogen
possible human carcinogen
not classifiable as to human carcinogenicity
evidence of non-carcinogenicity for humans.
The EPA has not classified either phenoxy herbicides or TCDD as to carcinogenicity.

In conclusion, evidence linking agent orange to pancreatic cancer is limited and not suggestive as per the Insittutte of Medicine. None of the medical conditions listed in this medical record a result of Agent Orange exposure during the Vietnam War. More and information on how disability questions are handled can be found at the IOM site referenced below.

Howard Frumkin, Agent Orange and Cancer: An Overview for Clinicians, CA – A Cancer Journal for Clinicians (Vol. 53; 4: 245-255

Bertazzi PA, Consonni D, Bachetti S, et al. Health effects of dioxin exposure: a 20-year mortality study . Am J Epidemiol 2001; 153: 1031-1044.

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