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Agent Orange and Vietnam Related Research

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Agent Orange and Vietnam Related Research

Agent Orange Brief

Agent Orange and Vietnam Related Research

VA Projects

Vietnam Veterans Mortality Study (Proportionate Mortality Study of Army and Marine Corps Veterans of the Vietnam War) - The results of this (rate-of-death) study were released in September 1987. Patterns of mortality among 24,235 Army and Marine Corps Vietnam veterans were compared with that of 25,685 non-Vietnam veterans using standardized proportional mortality ratios. The study subjects were a random (representative) sample of deceased Vietnam era veterans identified in a VA computerized benefit file. Military service information was obtained from military personnel records, and cause of death information from death certificates.

Statistically significant excess deaths were observed among Army Vietnam veterans for motor vehicle accidents, non-motor vehicle accidents and accidental poisonings. Similar findings have been reported in other studies of Vietnam veterans. Suicides were not elevated among Vietnam veterans. Marine Corps Vietnam veterans appeared to have an increased mortality from lung cancer and non-Hodgkin's lymphomas compared to Marines who did not serve in Vietnam. The study did not investigate possible causes of these findings. The study was published in the Journal of Occupational Medicine in May 1988.

Follow-up Proportionate Mortality Study of Army and Marine Corps Veterans of the Vietnam War - This updates the Vietnam Veterans Mortality Study. The initial effort included Vietnam-era veterans who died during the 1965-82 period. The updates include deaths through 1984. Compared to non-Vietnam veterans, soldiers and Marines who served in Vietnam had a small but statistically significant excess of deaths from external causes. Army Vietnam veterans had small excesses of laryngeal cancer and lung cancer, but the role of such known causes as smoking could not be determined. The study was published in the Journal of Occupational Medicine in July 1991.

Proportionate Mortality Among US Army Vietnam Veterans Who Served in I Corps - This study was designed to determine whether Army veterans, who were stationed in the same geographical area in Vietnam as Marine veterans, experienced mortality patterns similar to these Marines. The post-service mortality experience of 6,668 Army veterans who served in Military Region I, also known as "I Corps," was compared to that of 27,917 Army non-Vietnam veterans.

Statistically significant excesses of deaths were observed for motor vehicle accidents and accidental poisonings. Deaths due to other major disease categories, including malignant neoplasms, and suicides were no more frequent among Army I Corps veterans than their counterparts. No significant excess of deaths due to non-Hodgkin's lymphomas or lung cancer was observed. The study results were published in the American Journal of Epidemiology in October 1990. This was a follow-up research project in response to results of the Vietnam Veterans Mortality Study.

Soft Tissue Sarcoma Study (Soft Tissue Sarcoma and Military Service in Vietnam: A Case Control Study) - This study was conducted of men who were of draftable age during the Vietnam conflict to examine the association of soft tissue sarcomas (a form of cancer) with military service in Vietnam as well as other environmental risk factors. A total of 217 soft tissue sarcoma cases selected from the Armed Forces Institute of Pathology were compared to 599 controls for Vietnam service occupational and non-occupational exposure to various chemicals, occupational history, medical history, and life-style (smoking, alcohol, coffee, etc.). The results of the study indicate that Vietnam veterans did not have an increased risk of soft tissue sarcomas when compared to those men who had never been in Vietnam. The study was published in the Journal of the National Cancer Institute in October 1987.

Soft Tissue Sarcoma Review (Soft Tissue Sarcomas and Military Service in Vietnam: A Case Comparison Group Analysis of Hospital Patients) - This study reviewed soft tissue sarcoma cases among Vietnam era veterans who were admitted to VA medical centers during the period 1969-1983. This effort compared location, histopathology and relative frequency of soft tissue sarcomas between Vietnam veterans and non-Vietnam veterans. The study showed that for this group of veterans, service in Vietnam did not increase the risk of developing this type of cancer. The VA's Office of Environmental Epidemiology, now known as the Environmental Epidemiology Service, worked with the VA's Pathology Service on this research. The findings were published in the Journal of Occupational Medicine in December 1986.

Adipose Tissue Study (Dioxins and Dibenzofurans in Adipose Tissue of U.S. Vietnam Veterans and Controls) - VA, in collaboration with the Environmental Protection Agency (EPA), completed a very detailed analysis of adipose (fat) tissue specimens from 195 men of the Vietnam era age group. The specimens were analyzed for 2,3,7,8-TCDD, the contaminant found in one of the ingredients of Agent Orange, and sixteen other related dioxins and dibenzofurans. Researchers used adipose tissue collected for the EPA's National Human Adipose Tissue Survey. A total of 36 Vietnam veterans, 79 veterans who did not serve in Vietnam, and 80 civilians were selected and their archived tissues were analyzed.

Investigators found that the average level of 2,3,7,8-TCDD in adipose tissue of Vietnam veterans was not significantly different from that of the non-Vietnam veterans or the civilians. This was the case both with and without adjustment for several demographic variables. Furthermore, the results showed no association between TCDD levels and Agent Orange exposure opportunity estimations based on military records. The study was published in the American Journal of Public Health in March 1991.

National Vietnam Veterans Readjustment Study - This study found that a majority of Vietnam theater veterans have made a successful re-entry to civilian life and currently experience few symptoms of post-traumatic stress disorder (PTSD) or other readjustment problems. Although in general, male Vietnam theater veterans do not differ greatly in their current life adjustment from their era veteran counterparts, there is some evidence that female theater veterans currently experience more readjustment problems than other Vietnam era veteran women of similar age and military occupation. The study found that 15.2 percent of all male Vietnam veterans and 8.5 percent of Vietnam veteran women currently suffer from PTSD. The study also indicated that PTSD in the Vietnam veteran population is associated with significant levels of morbidity (illnesses), reflected in higher levels of unemployment, family and educational difficulties. The rates of PTSD are higher for black and Hispanic veterans than among white veterans.

Combat Experience and Postservice Psychosocial Status as Predictors of Suicide in Vietnam Veterans - Potential risk factors for suicide among 38 Vietnam veterans were examined using Vietnam veterans who died from motor vehicle accidents as a comparison group. Veterans were selected from Los Angeles County Medical Examiner's files.

No military service factor was associated with suicide. The characteristics of Vietnam veteran's suicide cases were not substantially different from non-Vietnam veterans' suicides with respect to known demographic risk factors. The psychological profile for Vietnam veteran suicide cases was also similar to non-Vietnam veteran suicide cases in most instances. Symptoms related to PTSD were observed more frequently among suicide cases than accident cases. However, suicides were not associated with specific combat experiences or military occupation. The extent of combat experience in Vietnam per se as measured in this study was not a good predictor of suicide death. These results were published in the Journal of Nervous and Mental Disease in January 1990.

Army Chemical Corps Study - This study examined health effects of chemical exposures during military service in Vietnam among men assigned to Army chemical units, which were responsible for detecting and counteracting enemy chemical warfare by using riot control agents and for defoliating vegetation using herbicides, including Agent Orange. Because they were involved in the mixing and application of these chemicals, these men were likely to have had heavier exposure than ground troops. The U.S. Army and Joint Services Environmental Support Group identified nearly 1,000 men who served in Army chemical units in Vietnam between 1965 and 1971 from unit morning reports. Fifty-three deaths were observed through December 1987. Based on rates for U.S. men adjusted for race, age, and calendar period, there were statistically significant excesses of digestive disease deaths, primarily due to alcohol-related diseases, and from motor vehicle accidents. Two deaths were observed from leukemia (with 0.5 expected) and two from brain cancer (0.4 expected). A total of 257 of the veterans had received VA inpatient care and/or the VA Agent Orange Registry medical examinations during the study period. Two veterans had confirmed diagnoses of Hodgkin's disease (0.7 expected).

Because of the small study group size and the lack of specificity of information regarding exposure, these results cannot be attributed to any single chemical agent. The study results were published in the American Journal of Industrial Medicine in December 1990.

Non-Hodgkin's Lymphoma Among Vietnam-era Veterans - This was a hospital-based case-control study undertaken to examine the association between military service in Vietnam and non-Hodgkin's lymphomas. The case group of about 201 Vietnam-era veterans who were treated in VA medical centers between 1969 and 1985 with diagnoses of non-Hodgkin's lymphomas was compared with 358 Vietnam-era veterans with diagnoses other than malignant lymphomas.

Military service in Vietnam did not increase the risk of non-Hodgkin's lymphomas either in general or with increased latency (delay) period, defined as the duration in years from the first service in Vietnam to hospital discharge. Service in a specific military branch, a specific region of Vietnam, or combat role (as determined by military occupational specialty) was not associated with any increased risk of non-Hodgkin's lymphomas. The study was published in the Journal of Occupational Medicine in July 1991.

A Case Control Analysis of Post-Traumatic Stress Disorder Among Vietnam Veterans in the Agent Orange Registry - This case control study compared demographic and military variables of 374 Vietnam veterans with PTSD diagnoses with a similar number of Vietnam veterans who did not have PTSD. All of these veterans were selected from the VA Agent Orange Registry, a computerized database of about 220,000 Vietnam veterans who voluntarily reported to a VA health care facility for a medical examination. (For more information about the VA Agent Orange Registry, see Agent Orange Brief, B1.) Cases and controls were matched by age, year of Agent Orange Registry examination, and race. Investigators confirmed that being wounded in Vietnam and having a combat job in Vietnam were risk factors for PTSD. Data analysis also revealed that those who had noncombat jobs but were wounded had the highest risk of PTSD. The study was published in the Annals of Epidemiology in November 1991.

Women Vietnam Veterans Mortality Study - Approximately 4,500 women Vietnam veterans and 6,500 women veterans who never served in Vietnam were identified from military records and followed for vital status on December 31, 1987. Investigators found that women Vietnam veterans had lower than expected mortality from all causes compared to U.S. women non-Vietnam veterans. Suicide rates were about the same in both groups. There was a slight excess of mortality from external causes among women Vietnam veterans compared with non-Vietnam veterans, primarily due to an excess of motor vehicle accidents. In comparison to U.S. women, mortality from cancers of the pancreas and uterine corpus was elevated among women Vietnam veterans but the increase was not statistically significant. The study results were published in the American Journal of Epidemiology in November 1991. This study was updated by extending the follow-up period of vital status to December 31, 1991. The results, which are consistent with the earlier findings, were published in the Journal of Occupational Medicine in March 1995.

Hodgkin's Disease and Vietnam Service - This hospital-based case-control study examined the association between military service in Vietnam and several histologic types (different forms) of malignant lymphomas. Earlier studies that showed an association between exposure to phenoxy herbicides, such as Agent Orange, and the risk of malignant lymphomas sparked concerns among Vietnam veterans about Agent Orange exposure. This is a report of 283 Vietnam-era veteran patients with a diagnosis of Hodgkin's disease who were treated in one of the 172 VA hospitals from 1969 to 1985. The controls consisted of 405 Vietnam-era veterans with a diagnosis other than malignant lymphoma.

Military service information was obtained from a review of veterans' military personnel records. Cases and controls were compared with respect to service in Vietnam and surrogate (estimated) measures of potential Agent Orange exposure. Investigators found that service in Vietnam was not associated with any significant increase in the risk of Hodgkin's disease. Furthermore, surrogate measures of potential Agent Orange exposure, such as service in a specific military branch, in a certain region within Vietnam, in a combat role, or extended Vietnam service time, were not associated with any significant increased risk of Hodgkin's disease. The results were published in the Annals of Epidemiology in September 1995.

Military Service in Vietnam and the Risk of Death from Trauma and Selected Cancers - This study compared the postservice mortality of 10,716 U.S. Marine veterans who served in Vietnam with that of 9,346 Marine veterans who did not serve in Vietnam. There was a significant excess of death for Vietnam Marines from all causes (combined) and all external causes (combined). After adjustments for age and rank in military, overall mortality continued to be statistically significant for Vietnam Marines compared to non-Vietnam Marines. The excess overall mortality was mainly due to excess deaths from external causes.

The risks for several site-specific cancers were elevated but not statistically significant. Investigators suggested that follow-up of this Marine cohort continue to determine whether there are statistically significant differences in the mortality patterns of Marine Vietnam and non-Vietnam veterans, especially for cancers. The results were published in the Annals of Epidemiology in September 1995.

A Review of NVVRS Data for Women Vietnam Veterans - VA, by means of a contract with the Research Triangle Institute (RTI), completed the National Vietnam Veterans Readjustment Study (NVVRS). The 3,106 study subjects included 950 women (431 Vietnam veterans, 304 non-Vietnam veterans, and 215 civilians). In addition to a 3-5 hour interview, some Vietnam and non-Vietnam veterans underwent a follow-up clinical interview with an expert mental health clinician. There were 86 women Vietnam veterans and 35 women non-Vietnam veterans in the group that received the follow-up interview. There is already an extensive report on the study design, statistical methods, and results by the RTI.

This follow-up analysis is focusing on women veterans. They are being evaluated by military service characteristics, such as occupation (nurse vs. non-nurse), length of service, branch, rank, and career status. Other characteristics, including age, race, substance abuse, and family history of violence are being considered and adjusted for in the analysis. All the data files, analysis files, and documentation necessary for the project have been obtained from the RTI.

An abstract was completed and sent to the U.S. House and Senate Committees on Veterans' Affairs on October 29, 1996. The analysis confirmed findings from the NVVRS of an increased risk of developing PTSD, depressive episodes, and alcohol abuse among women who served in Vietnam compared to women who served elsewhere. However, nurses serving in Vietnam were not at any higher risk than non-nurses in Vietnam for developing any of these three post war psychological problems other than depressive episodes which showed an elevated but non-significant risk associated with nursing in Vietnam.

Mortality Patterns among Vietnam Veterans - A 24-Year Retrospective Analysis - This project is the second update of the Vietnam Veterans Mortality Study. The mortality experience of 33,833 U.S. Army and Marine Corps Vietnam veterans who died during 1965-1988 was compared with that of 36,797 deceased non-Vietnam veterans using proportionate mortality ratios (PMR). Military service information was abstracted from military personnel records and cause of death information recorded from death certificates.

Army Vietnam veterans had statistically significant excesses of deaths from laryngeal cancer and lung cancer. There was an excess of external causes, including motor vehicle accidents and accidental poisonings. In contrast to Army veterans, the results for Marine Vietnam veterans varied according to the referent population used. When compared with non-Vietnam veterans, Marine Vietnam veterans had significantly elevated PMRs for lung cancer and skin cancer. There was also a significant excess of external causes of death, accidental poisonings and homicides compared with all non-Vietnam veterans. The results were published in the Journal of Occupational Medicine in March 1996.

Army Chemical Corps Vietnam Veterans Study Update - This study is an update of an investigation published in the American Journal of Industrial Medicine in December 1990. The original mortality study was expanded to include Army Vietnam-era veterans who were identified by the Defense Manpower Data Center with a chemical primary military occupational specialty or MOS code and by class rosters (1965-72) obtained from the Army Chemical School of Ft. McClellan.

These additional study subjects increase the size of the original Vietnam chemical cohort and provided a comparison group of Army Chemical Corps veterans who never served in Vietnam. The study results were published in the American Journal of Industrial Medicine in early 1997. The results of the analysis comparing the Vietnam cohort support the earlier study's finding of a significant excess of deaths from digestive diseases primarily due to liver cirrhosis. Non-significant elevated relative risks were observed for all cancers combined, digestive and respiratory systems cancer, skin cancer, lymphopoietic cancers, and respiratory system diseases. Compared to the mortality rates in the general population, the non-Vietnam Army Chemical Corps Chemical Corps veterans had a statistically significant deficit in mortality from all causes combined, which is consistent with a "healthy selection bias" seen among military populations.

Army Chemical Corps Vietnam Veterans Health Study - In July 1997, VA announced a research initiative designed to determine whether it is possible to conduct a large-scale study of the long-term health effects of exposure to Agent Orange (and other herbicides used in Vietnam) on Army Chemical Corps Vietnam veterans.

For the pilot study, letters were sent to 500 randomly selected veterans inviting them to participate in this investigation. Researchers selected study participants carefully to ensure that possible biases are minimized, if not eliminated. Study participants could not recruit or volunteer themselves. Half of the letters were sent to Vietnam veterans, and half were sent to Vietnam era veterans who did not serve in Vietnam.

The results of the 405 telephone interviews and 95 serum dioxin measurements conducted during the pilot study were presented to the study oversight committee in October 1998. The pilot study demonstrated that the Army Chemical Corps Vietnam era veterans could be located and were willing to participate in this telephone health interview.

The overall completion rate was 83%. The data also confirmed the fact that these men, often with assistance from their wives, were able to provide considerable detail on the reproductive details for pregnancies of offspring they had fathered. Serum concentrations of dioxins were found to be significantly correlated with the self-reported history by the veteran that he actually participated in the spraying of herbicides during their Vietnam service. Based on these findings the advisory committee voted to have the investigators proceed with the main study. The findings of the pilot study were published in Chemosphere in 2001.

The main study, which began in February 1999, included 2,247 Vietnam and 2,242 non-Vietnam veterans from the original the Army Chemical Corps cohort who were still living and not selected for the pilot study. The main phase of the study has been completed, and a manuscript has been submitted for publication. This phase involved an analysis of the health outcome data utilizing a history of spraying herbicides in Vietnam as a surrogate measure of Agent Orange exposure.

Agent Orange Registry Review for Testicular Cancer - All men who had their initial Agent Orange Registry examination between 1983 and 1987, and who had a confirmed diagnosis of testicular cancer were potential candidates for this project. Controls were selected from the Agent Orange Registry group matched to the case group by age, year of initial examination, and race. Military records were sought for all cases and controls and abstracted to obtain information on dates of military service, dates served in Vietnam, unit addresses, and military occupations in Vietnam.

Case-control analyses examined the relationship between specific Vietnam service characteristics and testicular cancer. The study results are not consistent with the hypothesis that Agent Orange may be a risk factor for testicular cancer among Vietnam veterans. The study results were published in the Annals of Epidemiology in January 1994.

The Risk of Suicide among Wounded Vietnam Veterans - This study was undertaken to determine whether an association exists between combat trauma and risk of postservice suicide among Vietnam veterans. The risk of suicide for 34,534 veterans who were wounded in Vietnam was evaluated for severity of wound and the number of times wounded. Investigators found that there was a trend of increasing risk of suicide with increased occurrence of combat trauma. The highest relative risk was observed for those veterans who were wounded more than once and hospitalized for a wound. In comparison with the U.S. male general population, veterans hospitalized because of a combat wound or wounded more than once had a significantly increased risk of suicide. Those wounded more than once and hospitalized had the highest increased risk of suicide. The study results were published in the American Journal of Public Health in May 1996.

A Case-Control Study of Lung Cancer Among Vietnam Veterans - Because of concerns about Agent Orange exposure, VA conducted a series of studies of specific cancers among Vietnam veterans. Lung cancer was the topic of investigation in this report.

The VA's Patient Treatment File (PTF) was used to identify 329 Vietnam era veterans with a diagnosis of lung cancer made between 1983 and 1990. The PTF is a computerized hospitalized database of inpatient records, including patient's demographic data, and diagnoses. A record is created for each inpatient discharged from all VA medical centers. Variables abstracted from the military record include education, race, branch of service, Military Occupational Specialty Code, rank, and units served within Vietnam. Two hundred sixty-nine controls were randomly selected from the PTF file of men hospitalized for a reason other than cancer. A second control (or comparison) group of 111 patients with colon cancer was also selected from the PTF. Data were also gathered on exposure to Agent Orange through the location of each individual ground troop veteran's unit in relation to an area sprayed and the time elapsed since the area was sprayed. Researchers found increased lung cancer mortality in Vietnam veterans. This study was published in the Journal of Occupational and Environmental Medicine in August 1997.

Posttraumatic Stress Disorder and the Risk of Traumatic Deaths Among Vietnam Veterans - This study evaluated whether an association exists between posttraumatic stress disorder (PTSD) and traumatic deaths among Vietnam veterans. Mortality risk of 4,247 Vietnam veterans from the VA Agent Orange Registry (AOR) with a diagnosis of PTSD relative to that of 12,010 Vietnam veterans from the AOR with no diagnosis of PTSD was calculated. Mortality experience of both groups was also compared with U.S. males. The veterans with PTSD were more likely than non-PTSD veterans to die from suicide and from accidental poisoning. Among Vietnam veterans on the AOR, PTSD is associated with a significant increased risk for suicide and accidental poisoning. The study results were published in the Journal of Nervous and Mental Disease in November 1994.

Women Vietnam Veterans Reproductive Health Study - Studies of reproductive outcomes among male veterans have been mostly negative in that service in Vietnam was not associated with the risk of fathering a child with birth defects. Although the results of male Vietnam veterans' health studies are useful in assessing the general health of women Vietnam veterans, further investigation may be necessary in the areas of gender specific health outcomes of women and of the birth outcomes of their children. It is well documented that maternal exposures are more commonly associated with adverse reproductive outcomes than paternal exposures.

This research compared the reproductive health outcomes of 4140 women Vietnam veterans with those of an equal number of women veterans who did not serve in Vietnam. Information on exposure was collected from telephone interviews and supplemented with and validated by military personnel records. Data on the birth outcomes were collected from telephone interviews and validated by reviews of medical and hospital records.

Although 8% of the women Vietnam veterans and 7.1% of the non-Vietnam veterans reported that they had a cancer of the reproductive organs, namely, breast, ovaries, uterus, or cervix, the difference was not statistically significant, either for the individual sites or for the reproductive organs as a group. There were no statistical differences between the two groups in the proportion of pregnancies resulting in miscarriage or stillbirth, low birth weight, pre-term delivery, or infant death.

Women Vietnam veterans, however, reported significantly more babies with birth defects and with severe birth defects. Over-reporting by women Vietnam veterans is not considered a likely explanation for these findings. AS a result of this study, legislation (Public Law 106-419) was enacted to provide certain benefits and services for women Vietnam veterans with certain "covered" birth defects.

The data on the prevalence of gynecologic cancers among female Vietnam veterans was published in the Journal of Occupational and Environmental Medicine in November 2000. A follow-up study of the birth defect data among the offspring of women who served in Vietnam is being conducted by obtaining detailed medical records for each reported birth defect.

Where can a veteran obtain additional information on VA Agent Orange research and studies on related matters?

Information on these subjects can be obtained at the VA medical center libraries, from the Environmental Health Clinician or Environmental Health Coordinator at every VA medical center, or from the Environmental Agents Service (131), Department of Veterans Affairs, 810 Vermont Avenue, N.W., Washington, DC 20420.

Where is additional information on Agent Orange-related issues available?

The following Agent Orange Brief fact sheets (including the one that you are reading) are available at VA medical centers nationwide and on-line at www.va.gov/AgentOrange: A1. Agent Orange General Information; A2.Agent Orange Class Action Lawsuit; B1.Agent Orange Registry; B2.Agent Orange - Health Care Eligibility; B3.Agent Orange and VA Disability Compensation; B4.VA Information Resources on Agent Orange and Related Matters; C1.Agent Orange - The Problem Encountered in Research; C2.Agent Orange and Vietnam Related Research - VA Projects; C3.Agent Orange and Vietnam Related Research - Non-VA Projects; D1.Agent Orange and Birth Defects; D2.Agent Orange and Chloracne; D3.Agent Orange and Non-Hodgkin's Lymphoma; D4.Agent Orange and Soft Tissue Sarcomas; D5.Agent Orange and Peripheral Neuropathy; D6.Agent Orange and Hodgkin's Disease; D7.Agent Orange and Porphyria Cutanea Tarda; D8.Agent Orange and Multiple Myeloma; D9.Agent Orange and Respiratory Cancers; D10.Agent Orange and Prostate Cancer; D11.Agent Orange and Spina Bifida; D12.Agent Orange and Diabetes; and D13.Agent Orange and Chronic Lymphocytic Leukemia.

Also at the same Web site you will find copies of past and current issues of the "Agent Orange Review" newsletter and other items of interest.

This fact sheet was updated in August 2005 and does not include any subsequent developments.