Agent Orange Exposure and Monoclonal Gammopathy of Undetermined Significance: An Operation Ranch Hand Veteran Cohort Study.
OBJECTIVE
Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans.


OBJECTIVE
To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans.


METHODS
This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS.


METHODS
Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002.


METHODS
Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs.


RESULTS
The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P=.007).


CONCLUSIONS
Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.
National Cancer Institute, National Institutes of Health, Bethesda, Maryland2Memorial Sloan Kettering Cancer Center, New York, New York.
Ola
O
Landgren
Agency for Toxic Substances and Disease Registry, Atlanta, Georgia.
Youn K
YK
Shim
Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio.
Joel
J
Michalek
National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Rene
R
Costello
National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Debra
D
Burton
Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio.
Norma
N
Ketchum
Clinical Center, National Institutes of Health, Bethesda, Maryland.
Katherine R
KR
Calvo
National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
Neil
N
Caporaso
Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark.
Elizabeth
E
Raveche
Agency for Toxic Substances and Disease Registry, Atlanta, Georgia.
Dan
D
Middleton
Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland.
Gerald
G
Marti
National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Robert F
RF
Vogt
D015085:2,4,5-Trichlorophenoxyacetic Acid / Q000009:adverse effects*; D015084:2,4-Dichlorophenoxyacetic Acid / Q000009:adverse effects*; D000368:Aged; D000369:Aged, 80 and over; D000075182:Agent Orange; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D006540:Herbicides / Q000009:adverse effects*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D009101:Multiple Myeloma / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000453:epidemiology; D016273:Occupational Exposure / Q000009:adverse effects*; D016017:Odds Ratio; D000072317:Polychlorinated Dibenzodioxins / Q000009:adverse effects* / Q000097:blood; D015995:Prevalence; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D058014:Veterans Health; D047829:Vietnam Conflict
D015415:Biomarkers; D006540:Herbicides; D000072317:Polychlorinated Dibenzodioxins; D015084:2,4-Dichlorophenoxyacetic Acid; D000075182:Agent Orange; D015085:2,4,5-Trichlorophenoxyacetic Acid