C
Epidemiologic Studies of Vietnam Veterans Health
Table C-1 provides an overview of design aspects of the epidemiologic studies related to Vietnam veterans’ health reviewed in the Institute of Medicine’s Veterans and Agent Orange report series (IOM, 1994, 1996, 1999, 2001, 2003, 2005). The summaries include the study’s design type, the numbers of subjects in the study and comparison populations, and a synopsis of how subjects were selected, how data were collected, what inclusion criteria were used, and how exposure was determined. The table was excerpted from Appendix A of the Veterans and Agent Orange: Update 2004 report. More information on these studies may be found in the reports referenced.
TABLE C-1 Epidemiologic Studies of Vietnam Veterans
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
UNITED STATES STUDIES |
||||
AFHS Studies Reviewed in Update 2004 |
||||
Akhtar et al., 2004 |
Cohort |
Follow-up to Ketchum et al. (1999), comparing cancer incidence among Ranch Hands with Vietnam veterans who served in Southeast Asia but did not spray herbicides and with U.S. national cancer rates |
1,189 net Ranch Hands for external analysis; 1,009 net Ranch Hands for internal analysis |
1,776 net comparison subjects for external analysis; 1,429 net comparison subjects for internal analysis |
Barrett et al., 2003 |
Cohort |
Serum TCDD measurement and psychological functioning among Ranch Hand veterans |
1,109 |
1,493 |
Michalek et al., 2003 |
Cohort |
Correlation for TCDD elimination and Ranch Hands with diabetes |
343 |
No comparison group |
Pavuk et al., 2003 |
Cohort |
Study to examine the relationship between serum TCDD and thyroid function in Ranch Hand veterans |
1,009 |
1,429 |
AFHS Studies Reviewed in Update 2002 |
||||
Barrett et al., 2001 |
Cohort |
Based on tests of cognitive functioning in 1982 and dioxin concentrations measured in 1987 and 1992, analyzed association between serum dioxin levels and cognitive functioning |
937 Ranch Hands |
1,052 Ranch Hand comparisons |
Michalek et al., 2001a |
Cohort |
Based on physical examination through 1992 and medical records reviewed through March 1993, association between serum dioxin levels and hepatic abnormality |
1,109 Ranch Hands |
1,493 Ranch Hand comparisons |
Michalek et al., 2001b |
Cohort |
Based on physical examination in 1982, 1985, 1987, 1992, and 1997, and medical records through 1997, association between serum dioxin and peripheral neuropathy |
761 Ranch Hands |
1,086 Ranch Hand comparisons |
Michalek et al., 2001c |
Cohort |
Based on physical examination in 1982, 1985, 1987, and 1992, and medical records through 1997, association between serum dioxin and hematologic function |
953 Ranch Hands |
1,280 Ranch Hand comparisons |
Steenland et al., 2001 |
Cohort |
Reexamine and compare diabetes data from the NIOSH cohort and the United States Air Force (USAF) Ranch Hands in order to reconcile differences between the two study methods and protocols |
267 NIOSH workers; 990 Ranch Hands |
227 NIOSH comparisons 1,275 Ranch Hand comparisons |
AFHS Studies Reviewed in Update 2000 |
||||
AFHS, 2000 |
Cohort |
266 health-related endpoints, including assessments of 10 clinical areas: general health, neoplasia, neurologic, psychologic, gastrointestinal, cardiovascular, hematologic, endocrine, immunologic, pulmonary |
995 |
1,299 |
Longnecker and Michalek, 2000 |
Cohort |
Based on physical examination and medical records review through 1992, association between serum dioxin and diabetes mellitus among comparison group (no Ranch Hands) |
— |
1,197 |
Ketchum et al., 1999 |
Cohort |
Based on physical examination and medical records review through 1992, association between serum dioxin and cancer, skin cancer, cancer other than skin cancer |
980 Ranch Hands |
1,275 Ranch Hand comparisons |
Michalek et al., 1999a |
Cohort |
Further elucidate relationship between dioxin and diabetes mellitus, effect of dioxin body burden on sex-hormone-binding globulin and insulin and fasting glucose |
871 Ranch Hands |
1,121 Ranch Hand comparisons |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
Michalek et al., 1999b |
Cohort |
Based on physical examinations in 1982, 1985, 1987, and 1992, immunologic response and exposure to dioxin among Ranch Hand and comparison cohorts |
914 Ranch Hands 372 (lymphocyte counts conducted) |
1,186 Ranch Hand comparisons 491 (lymphocyte counts conducted) |
Burton et al., 1998 |
Cohort |
Based on physical examination and medical record review through 1992, association between serum dioxin and occurrence and timing (relative to Southeast Asia service) of chloracne and acne |
930 Ranch Hands |
1,200 Ranch Hand comparisons |
Michalek et al., 1998b |
Cohort |
Updates, all-cause and cause-specific post-service mortality (through 1993) among veterans of Operation Ranch Hand, using standardized mortality ratios |
1,261 Ranch Hands |
19,080 Ranch Hand comparisons |
Michalek et al., 1998c |
Cohort |
Prospective study, exposure and long-term health, survival, reproductive outcome |
1,208 veterans; 903 offspring |
1,549 veterans; 1,254 offspring |
Michalek et al., 1998d |
Cohort |
Third report in a series investigating dioxin body burden and preterm birth, intrauterine growth retardation, infant death among offspring of Ranch Hand veterans |
859 |
1,223 |
AFHS Studies Reviewed in Update 1998 |
||||
Michalek et al., 1998a |
Cohort |
Paternal serum dioxin levels and infant death among Ranch Hand offspring |
859 children: 323 background exposure; 267 low exposure; 269 high exposure |
1,223 children |
Henriksen et al., 1997 |
Cohort |
Relationship between serum dioxin and glucose, insulin, and diabetes mellitus in Ranch Hands through 1992 |
989 |
1,276 |
AFHS, 1996; Michalek et al., 1998b |
Cohort |
Mortality update, Ranch Hands through the end of 1993 in the AFHS cohort (1983, 1984b, 1985, 1986, 1989, 1991a, 1995) |
1,261 |
19,080 |
Henriksen et al., 1996 |
Cohort |
Serum dioxin and reproductive hormones in Ranch Hands, 1982, 1985, 1987, and 1992 |
1,045 participants (1982); 474 provided semen |
1,224 participants (1982); 532 provided semen |
AFHS Studies Reviewed in Update 1996 |
||||
AFHS, 1995 |
Cohort |
Mortality updates of Ranch Hands who sprayed herbicides in Vietnam, compared with USAF C-130 air and ground crew veterans in Southeast Asia who did not spray herbicides |
1,261, original cohort |
19,101, original cohort |
Wolfe et al., 1995 |
Cohort |
Paternal serum dioxin and reproductive outcomes of Ranch Hand veterans, compared with USAF veterans from Southeast Asia who did not spray herbicides |
932 |
1,202 |
AFHS Studies Reviewed in VAO |
||||
AFHS, 1992 |
Cohort |
Reproductive outcomes of AFHS participants |
791 |
942 |
AFHS, 1984a, 1987, 1990, 1991b |
Cohort |
Baseline morbidity, follow-up examination results |
1,208 baseline |
1,668 baseline |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
AFHS, 1983, 1984b, 1985, 1986, 1989, 1991a |
Cohort |
Mortality updates, Ranch Hands who sprayed herbicides in Vietnam, compared with USAF C-130 air and ground crew veterans in Southeast Asia who did not spray herbicides |
1,261 (original cohort) |
19,101 (original cohort) |
Michalek et al., 1990 |
Cohort |
Mortality of Ranch Hands, compared with USAF C-130 air and ground crew veterans in Southeast Asia |
1,261 |
19,101 |
Wolfe et al., 1990 |
Cohort |
Health status of Ranch Hands at second follow-up, compared with USAF C-130 air and ground crew veterans in Southeast Asia |
995 |
1,299 |
Centers for Disease Control and Prevention Studies Reviewed in VAO |
||||
Decoufle et al., 1992 |
Cohort |
Association between self-reported health outcomes and perception of exposure to herbicides based on Vietnam Experience Study |
7,924 |
7,364 |
O’Brien et al., 1991 |
Cohort |
Interview report and mortality for NHL based on Vietnam Experience Study |
8,170 |
7,564 |
CDC, 1990a |
Case-control |
Selected Cancers Study: population-based case-control study of all men born 1921–1953; cases diagnosed area covered by eight cancer registries, controls selected by random-digit dialing |
1,157 NHL; 342 STS; 310 HD; 48 nasal carcinoma; 80 nasopharyngeal carcinoma; 130 primary liver cancer |
1,776 |
CDC, 1990b |
Case-control |
Selected Cancers Study: population-based case-control study of all men born 1921–1953; cases diagnosed in area covered by eight cancer registries, controls selected by random-digit dialing for NHL |
1,157 |
1,776 |
CDC, 1990c |
Case-control |
Selected Cancers Study: STS |
342 |
1,776 |
CDC, 1990d |
Case-control |
Selected Cancers Study: HD, nasal cancer, nasopharyngeal cancer, primary liver cancer |
310 HD; 48 nasal carcinoma; 80 nasopharyngeal carcinoma; 130 primary liver cancer |
1,776 |
CDC, 1989b |
Cohort |
Vietnam Experience Study: random sample, U.S. Army enlisted men, 1965–1971 |
2,490 |
1,972 |
CDC, 1988a |
Cohort |
Vietnam Experience Study: random sample, U.S. Army enlisted men, 1965–1971, psychosocial outcomes |
2,490 |
1,972 |
CDC, 1988b |
Cohort |
Vietnam Experience Study: physical health outcomes |
2,490 |
1,972 |
CDC, 1988c |
Cohort |
Vietnam Experience Study: reproductive outcomes |
12,788 children |
11,910 children |
CDC, 1987; Boyle et al., 1987 |
Cohort |
Vietnam Experience Study: mortality |
9,324 |
8,989 |
Erickson et al., 1984 a,b |
Case-control |
CDC birth defects study, children born in the Atlanta, Georgia, area 1968–1980, comparing paternal Vietnam experience and potential Agent Orange exposure for birth defects cases and normal controls |
7,133 |
4,246 |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
Department of Veterans Affairs Studies Reviewed in Update 2002 |
||||
Kang et al., 2001 |
Cohort |
Health of Army Chemical Corps Vietnam veterans, compared with Army Chemical Corps veterans who did not serve in Vietnam |
2,872 |
2,737 |
Kang et al., 2000a |
Cohort |
Self-report pregnancy outcomes for female Vietnam veterans, compared with contemporary veterans not deployed to Vietnam; odds ratios calculated for reproductive history and various birth defects |
3,392 women; 1,665 women with indexed pregnancy |
3,038 women; 1,912 women with indexed pregnancy |
Kang et al., 2000b |
Cohort |
Gynecologic cancers among female Vietnam veterans, compared with veteran controls |
484 |
5,946 |
Department of Veterans Affairs Studies Reviewed in Update 1998 |
||||
Dalager and Kang, 1997 |
Cohort |
Morbidity and mortality experience (1968–1987), Army Chemical Corps Vietnam veterans, compared with U.S. men; extension of Thomas and Kang (1990) |
2,872 |
2,737 |
Mahan et al., 1997 |
Case-control |
Lung cancer among Vietnam veterans (1983–1990) |
329 |
269 111 |
McKinney et al., 1997 |
Cross-sectional |
Tobacco use in veterans and nonveterans by 1987 NMES |
15,000 |
— |
Bullman and Kang, 1996 |
Cohort |
Mortality of veterans with nonlethal (combat and noncombat) wounds sustained during the Vietnam war |
34,534 |
— |
Watanabe and Kang, 1996 |
Cohort |
Mortality experience (1965–1988) of Army and Marine Corps Vietnam veterans; extension of Breslin et al. (1988) and Watanabe et al. (1991) |
33,833 |
36,797 |
Dalager et al., 1995b |
Case-control |
HD cases diagnosed 1969–1985 among Vietnam-era veterans |
283 |
404 |
Watanabe and Kang, 1995 |
Cohort |
Postservice mortality among Marine Vietnam veterans |
10,716 |
9,346 |
Department of Veterans Affairs Studies Reviewed in Update 1996 |
||||
Dalager et al., 1995a |
Cohort |
Update of Thomas et al. (1991) through Dec. 31, 1995 |
4,586 |
5,325 |
Bullman et al., 1994 |
Case-control |
Association between testicular cancer and surrogate measures of exposure to Agent Orange in male Vietnam veterans |
97 |
311 |
Department of Veterans Affairs Studies Reviewed in VAO |
||||
Bullman et al., 1991 |
Case-control |
PTSD cases in Vietnam veterans, compared with Vietnam veterans without PTSD, for association with traumatic combat experience |
374 |
373 |
Dalager et al., 1991 |
Case-control |
NHL cases diagnosed 1969–1985 among Vietnam-era veterans, compared with cases of other malignancies among Vietnam-era veterans, for association with Vietnam service |
201 |
358 |
Eisen et al., 1991 |
Cohort |
Health effects in male monozygotic twins serving in the armed forces during Vietnam era (1965–1975) |
2,260 |
2,260 |
Thomas et al., 1991 |
Cohort |
Mortality experience (1973–1987) among female Vietnam veterans, compared with female non-Vietnam veterans and for each cohort compared with U.S. women |
4,582 |
5,324 |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
Watanabe et al., 1991 |
Cohort |
Mortality experience (1965–1984) in Army and Marine Corps Vietnam veterans, compared with: (1) branch-specific (Army and Marine) Vietnam-era veterans, (2) all Vietnam-era veterans combined, (3) the U.S. male population |
24,145 Army 5,501 Marines |
(1) 27,145 Army 4,505 Marines (2) 32,422 combined Vietnam era (3) U.S. male population |
Bullman et al., 1990 |
Cohort |
Mortality experience in Army I Corps Vietnam veterans, compared with Army Vietnam-era veterans |
6,668 deaths |
27,917 deaths |
Farberow et al., 1990 |
Case-control |
Psychological profiles, military factors associated with suicide and MVA fatalities in Los Angeles County Vietnam-era veterans (1977–1982) |
22 Vietnam suicides; 19 Vietnam-era suicides |
21 Vietnam MVA; 20 Vietnam-era MVA |
Thomas and Kang, 1990 |
Cohort |
Morbidity and mortality experience (1968–1987) in Army Chemical Corps Vietnam veterans compared with U.S. men |
894 |
— |
True et al., 1988 |
Cross-sectional |
PTSD and Vietnam combat experience among Vietnam-era veterans |
775 |
1,012 |
Breslin et al., 1988; Burt et al., 1987 |
Cohort |
Mortality experience (1965–1982) in Army and Marine Corps Vietnam veterans, compared with Vietnam-era veterans who did not serve in Southeast Asia, standardized by age and race; nested NHL case-control study |
24,235 |
26,685 |
Kang et al., 1987 |
Case-control |
STS cases (1975–1980) diagnosed at the Armed Forces Institute of Pathology (AFIP), compared with controls identified from patient logs of referring pathologists or their departments, for association with Vietnam service and likelihood of Agent Orange exposure |
217 |
599 |
Kang et al., 1986 |
Case-control |
STS (1969–1983) in Vietnam-era veterans, for association with branch of Vietnam service as a surrogate for Agent Orange exposure |
234 |
13,496 |
American Legion Studies Reviewed in VAO |
||||
Snow et al., 1988 |
Cohort |
PTSD in association with traumatic combat experience among American Legion members serving in Southeast Asia (1961–1975) |
2,858 |
Study group subdivided for internal comparison |
Stellman et al., 1988a |
Cohort |
Physical health, reproductive outcomes among American Legion members who served in Southeast Asia (1961–1975), for association with combat and herbicide exposure |
2,858 |
3,933 |
Stellman et al., 1988b |
Cohort |
Social, behavioral outcomes among American Legion members who served in Southeast Asia (1961–1975), association with combat and herbicide exposure |
2,858 |
3,933 |
State Studies Reviewed in Update 1998 |
||||
Clapp, 1997 |
Case-control |
Selected cancers identified (1988–1993) among Massachusetts Vietnam veterans, compared with Massachusetts Vietnam-era veterans with cancers of other sites; update of Clapp et al., 1991 |
245 |
999 |
State Studies Reviewed in Update 1996 |
||||
Visintainer et al., 1995 |
Cohort |
Mortality experience (1965–1971) in male Michigan Vietnam veterans, compared with non-Vietnam veterans from Michigan |
3,364 deaths |
5,229 deaths |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
State Studies Reviewed in VAO |
||||
Fiedler and Gochfeld, 1992; Kahn et al., 1992a,b,c |
Cohort |
New Jersey: outcomes in select group of herbicide-exposed Army, Marine, and Navy Vietnam veterans, compared with veterans self-reported as unexposed |
10 Pointman I 55 Pointman II |
17 Pointman I 15 Pointman II |
Clapp et al., 1991 |
Case-control |
Massachusetts: selected cancers identified (1982–1988) among Vietnam veterans, compared with Massachusetts Vietnam-era veterans with cancers of other sites |
214 |
727 |
Deprez et al., 1991 |
Descriptive |
Maine: Vietnam veterans, compared with atomic test veterans and general population, for health status and reproductive outcomes |
249 |
113 atomic test veterans |
Levy, 1988 |
Cross-sectional |
Massachusetts: PTSD in chloracne as indicator of exposure to TCDD; control Vietnam veterans |
62 |
5 |
Anderson et al., 1986a |
Cohort |
Wisconsin: mortality experience, veterans compared with nonveterans (Phase 1); mortality experience of Vietnam veterans and Vietnam-era veterans, compared with nonveterans and other veterans (Phase 2) |
110,815 white male veteran deaths; 2,494 white male Vietnam-era veteran deaths; 923 white male Vietnam veteran deaths |
342,654 white male non-veteran deaths; 109,225 white male other veteran deaths |
Anderson et al., 1986b |
Cohort |
Wisconsin: mortality experience in Vietnam-era veterans and Vietnam veterans, compared with U.S. men, Wisconsin men, Wisconsin nonveterans, and Wisconsin other veterans |
122,238 Vietnam-era veterans; 43,398 Vietnam veterans |
— |
Goun and Kuller, 1986 |
Case-control |
Pennsylvania: STS, NHL, selected rare cancer cases, compared with controls without cancer for Vietnam experience in men (1968–1983) |
349 |
349 deceased |
Holmes et al., 1986 |
Cohort |
West Virginia: mortality experience (1968–1983) of veterans, Vietnam veterans, Vietnam-era veterans, compared with nonveterans; Vietnam veterans compared with Vietnam-era veterans |
615 Vietnam veterans; 610 Vietnam-era veterans |
— |
Pollei et al., 1986 |
Cohort |
New Mexico: chest radiographs of Agent Orange Registry Vietnam veterans, compared with radiographs of control USAF servicemen, for pulmonary and cardiovascular pathology |
422 |
105 |
Kogan and Clapp, 1985, 1988 |
Cohort |
Massachusetts: mortality experience (1972–1983) among white male Vietnam veterans, compared with non-Vietnam veterans and all other nonveteran white males in Massachusetts |
840 deaths |
2,515 deaths in Vietnam-era veterans |
Lawrence et al., 1985 |
Cohort |
New York: mortality experience in (1) Vietnam-era veterans, compared with nonveterans and (2) Vietnam veterans, compared with Vietnam-era veterans |
(1) 4,558 (2) 555 |
17,936 941 |
Rellahan, 1985 |
Cohort |
Hawaii: health outcomes in Vietnam-era (1962–1972) veterans residing in Hawaii, associated with Vietnam experience |
232 |
186 |
Wendt, 1985 |
Descriptive |
Iowa: health effects and potential exposure to Agent Orange among veterans who served in Southeast Asia |
10,846 |
None |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
Greenwald et al., 1984 |
Case-control |
New York: STS cases, compared with controls without cancer for Vietnam service and herbicide exposure including Agent Orange, dioxin, or 2,4,5-T |
281 |
281 live controls; 130 deceased controls |
Newell, 1984 |
Cross-sectional |
Texas: preliminary (1) cytogenetic, (2) sperm, (3) immune response tests in Vietnam veterans, compared with controls |
(1) 30; (2) 32; (3) 66 |
(1) 30; (2) 32; (3) 66 |
Other U.S. Veterans Studies Reviewed in VAO |
||||
Tarone et al., 1991 |
Case-control |
Testicular cancer (18–42 years old) cases, January 1976–June 1981, compared with hospital controls, for association with Vietnam service |
137 |
130 |
Aschengrau and Monson, 1990 |
Case-control |
Cases with late adverse pregnancy outcomes compared with normal control births, for association with paternal Vietnam service (1977–1980) |
857 congenital anomalies 61 stillbirths; 48 neonatal deaths |
998 |
Goldberg et al., 1990 |
Cohort |
Male twin pairs who served in Vietnam era (1965–1975), for association between Vietnam service and PTSD |
2,092 |
2,092 |
Aschengrau and Monson, 1989 |
Case-control |
Association between husband’s military service and spontaneous abortion at or by 27 weeks, compared with women delivering at 37 weeks |
201 |
1,119 |
AUSTRALIAN VETERANS STUDIES |
||||
Australian Studies Reviewed in Update 2000 |
||||
AIHW, 1999 |
Cohort |
Validation of the male veterans study (CDVA, 1998a) by medical documents, doctors’ certification, records on a disease or death registry |
6,842 |
— |
CDVA, 1998a |
Cohort |
Self-reported data on male members of the Australian Defence Force and the Citizen Military Force who landed in Vietnam or entered Vietnamese water. Questions on physical (including reproductive history) and mental health, and that of their partner(s) and children |
49,944 mailed; 39,955 responded |
— |
CDVA, 1998b |
Cohort |
Self-reported data on female members of the Australian Defence Force and the Citizen Military Force who landed in Vietnam or entered Vietnamese water. Questions on physical (including reproductive history) and mental health, and that of their partner(s) and children |
278 mailed 225 responded |
— |
Australian Studies Reviewed in Update 1998 |
||||
Crane et al., 1997a |
Cohort |
Mortality experience (through 1994) of Australian veterans who served in Vietnam |
59,036 men 484 women |
— |
Crane et al., 1997b |
Cohort |
Mortality experience (through 1994) of Australian national servicemen who served in Vietnam |
18,949 |
24,646 |
O’Toole et al., 1996a,b,c |
Cross-sectional |
Survey of self-reported health status (1989–1990) of Australian Army Vietnam veterans |
641 |
— |
Australian Studies Reviewed in VAO |
||||
Field and Kerr, 1988 |
Cohort |
Tasmanian Vietnam veterans, compared with neighborhood controls for adverse reproductive and childhood health outcomes |
357 |
281 |
Reference |
Study Design |
Description |
Study Group (N) |
Comparison Group (N)* |
Fett et al., 1987a |
Cohort |
Mortality experience in Vietnam veterans, compared with Vietnam-era veterans through 1981 |
19,205 |
25,677 |
Fett et al., 1987b |
Cohort |
Cause-specific mortality experience in Vietnam veterans, compared with Vietnam veterans through 1981 |
19,205 |
25,677 |
Forcier et al., 1987 |
Cohort |
Mortality in Vietnam veterans by job classification, location, time of service |
19,205 |
Internal comparison |
Donovan et al., 1983, 1984 |
Case-control |
Congenital anomalies in children (1969–1979), compared with infants born without anomalies, for association with paternal Vietnam service |
8,517 |
8,517 |
OTHER VIETNAM VETERANS’ STUDIES |
||||
Other New Vietnam Veterans’ Studies Reviewed in Update 2004 |
||||
Kim H-A et al., 2003 |
Cohort |
Immunotoxicologic effects of Agent Orange exposure on Korean Vietnam veterans |
51 (24 veterans– patient; 27 veterans– normal) |
36 |
Kim J-S et al., 2003 |
Cross-sectional |
Agent Orange exposure and Korean Vietnam veterans |
1,224 |
154 |
Mo et al., 2002 |
Cohort |
Skin and general disease patterns among Korean Vietnam veterans |
332 |
None |
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