Agent Orange exposure and cancer incidence in Korean Vietnam veterans: A prospective cohort study

Yi, Sang-Wook; Ohrr, Heechoul

doi:10.1002/cncr.28961

Cited by 42 publications

(73 citation statements)

References 35 publications

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“…The most recent group in which associations have been estimated between Agent Orange exposure and risk of NHL, HL, and MM is the cohort of South Korean veterans of the Vietnam War [126,127]. Studies in this group include a cross-sectional analysis of self-reported cancer prevalence based on a postal survey completed by 114,562 veterans [126] and a retrospective cohort study of cancer incidence among 180,251 veterans linked to the national cancer incidence database [127].…”

Section: Methodsmentioning

confidence: 99%

“…Studies in this group include a cross-sectional analysis of self-reported cancer prevalence based on a postal survey completed by 114,562 veterans [126] and a retrospective cohort study of cancer incidence among 180,251 veterans linked to the national cancer incidence database [127]. Potential exposure to Agent Orange was evaluated based on the proximity of the respondent's division or brigade (and, in the cross-sectional study, based on the proximity of the respondent's self-reported battalion or company) to sprayed areas, using the Agent Orange Exposure Opportunity Index model E4 developed by Stellman et al [128].…”

Section: Methodsmentioning

confidence: 99%

“…Both the studies are also undermined by untrustworthy exposure data [126,127]. Among 102 South Korean veterans of the Vietnam War in 2007, serum TCDD levels were not significantly correlated with self-reported perceived exposure to Agent Orange (r 2 ¼ 0.129), division-or brigade-level proximity-based exposure (r 2 ¼ 0.073), or battalion-or company-level proximity-based exposure (r 2 ¼ 0.159) [129].…”

Section: Methodsmentioning

confidence: 99%

“…In summary, none of the studies of Agent Orange or TCDD exposure and risk of NHL, HL, or MM among Vietnam veterans, including the Air Force Health Study [107,112,114,115], the Army Chemical Corps Study [120,121], the Selected Cancers Study [122,123], the VA hospitals study [124,125], and the South Korean veterans studies [126,127], offer credible evidence to support a causal association. The substantial limitations of these studies, including small size of the first two studies and the lack of valid estimates of Agent Orange exposure in the others, as well as probably invalid outcome information in the Korean cross-sectional study, prevent them from ruling out an association.…”

Section: Methodsmentioning

confidence: 99%

“…Estimated exposure to Agent Orange or TCDD was significantly (or nearly significantly) associated with increased MM incidence or mortality in some studies [126,165,173,182,183], including both of the Seveso cancer studies, but not in others [114,127,164,171,172].…”

Section: Consistencymentioning

confidence: 99%

See 4 more Smart Citations

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

Chang

Boffetta

Adami

et al. 2015

Annals of Epidemiology

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Consistencymentioning

confidence: 99%

See 3 more Smart Citations

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

Chang

Boffetta

Adami

et al. 2015

Annals of Epidemiology

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Exposure to Agent Orange and Risk of Bladder Cancer Among US Veterans

et al. 2023

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ImportanceTo date, limited data exist regarding the association between Agent Orange and bladder cancer, and the Institute of Medicine concluded that the association between exposure to Agent Orange and bladder cancer outcomes is an area of needed research.ObjectiveTo examine the association between bladder cancer risk and exposure to Agent Orange among male Vietnam veterans.Design, Setting, and ParticipantsThis nationwide Veterans Affairs (VA) retrospective cohort study assesses the association between exposure to Agent Orange and bladder cancer risk among 2 517 926 male Vietnam veterans treated in the VA Health System nationwide from January 1, 2001, to December 31, 2019. Statistical analysis was performed from December 14, 2021, to May 3, 2023.ExposureAgent Orange.Main Outcomes and MeasuresVeterans exposed to Agent Orange were matched in a 1:3 ratio to unexposed veterans on age, race and ethnicity, military branch, and year of service entry. Risk of bladder cancer was measured by incidence. Aggressiveness of bladder cancer was measured by muscle-invasion status using natural language processing.ResultsAmong the 2 517 926 male veterans (median age at VA entry, 60.0 years [IQR, 56.0-64.0 years]) who met inclusion criteria, there were 629 907 veterans (25.0%) with Agent Orange exposure and 1 888 019 matched veterans (75.0%) without Agent Orange exposure. Agent Orange exposure was associated with a significantly increased risk of bladder cancer, although the association was very slight (hazard ratio [HR], 1.04; 95% CI, 1.02-1.06). When stratified by median age at VA entry, Agent Orange was not associated with bladder cancer risk among veterans older than the median age but was associated with increased bladder cancer risk among veterans younger than the median age (HR, 1.07; 95% CI, 1.04-1.10). Among veterans with a diagnosis of bladder cancer, Agent Orange was associated with lower odds of muscle-invasive bladder cancer (odds ratio [OR], 0.91; 95% CI, 0.85-0.98).Conclusions and RelevanceIn this cohort study among male Vietnam veterans, there was a modestly increased risk of bladder cancer—but not aggressiveness of bladder cancer—among those exposed to Agent Orange. These findings suggest an association between Agent Orange exposure and bladder cancer, although the clinical relevance of this was unclear.

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Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel

Benhammou,

Leng,

Shah

et al. 2023

JAMA Netw Open

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ImportanceHepatocellular carcinoma (HCC) and its mortality are on the rise. Viral hepatitis and alcohol are leading risk factors; however, other risk factors among veterans are less defined, including Agent Orange (AO), an herbicide linked to several cancers.ObjectiveTo assess the association of AO exposure and HCC in a national cohort of Vietnam veterans.Design, Setting, and ParticipantsThis retrospective cohort study included Vietnam veterans who served between 1966 and 1975, were male, were older than 18 years at the time of deployment, and had established follow-up in the Veterans Affairs (VA) between 2000 and 2019. Veterans with AO exposure were identified in the disability data via validated clinical surveys. Relevant clinical risk factors for cirrhosis and HCC were collected. Patients were stratified based on cirrhosis status, as defined by consecutive diagnosis found by documented International Classification of Diseases, Ninth Revision and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision scores or calculated Fibrosis-4 scores. Data were collected from January 1, 2019, to December 31, 2020, and analyzed from December 2020 to October 2023.Main Outcome and MeasuresIncident HCC was the primary outcome. AO and HCC association was estimated using a multivariable Cox regression analysis, with death and liver transplant as competing events.ResultsOf the 296 505 eligible veterans (222 545 [75.1%] White individuals and 44 342 [15.0%] Black individuals), 170 090 (57%) had AO exposure (mean [SD] age, 21.62 [3.49] years; 131 552 White individuals [83.2%] and 22 767 Black individuals [14.4%]) and 35 877 (12.1%) had cirrhosis. Veterans who were not exposed to AO were more likely to smoke (109 689 of 126 413 [86.8%] vs 146 061 of 170 090 [85.9%]); use alcohol (54 147 of 126 413 [42.8%] vs 71 951 of 170 090 [42.3%]) and have viral hepatitis (47 722 of 126 413 [37.8%] vs 58 942 of 170 090 [34.7%]). In a multivariable competing risk model, AO exposure was not associated with HCC. Among veterans with cirrhosis, self-identification as Hispanic individuals (aHR, 1.51; 95% CI, 1.30-1.75; P &lt;.001) or Black individuals (aHR, 1.18; 95% CI, 1.05-1.32; P = .004), and having a diagnosis of viral hepatitis (aHR, 3.71; 95% CI, 3.26-4.24; P &lt;.001), alcohol-associated liver disease (aHR, 1.32; 95% CI, 1.19-1.46; P &lt;.001), and nonalcoholic fatty liver disease (NAFLD) (aHR, 1.92; 95% CI, 1.72-2.15; P &lt;.001) were associated with HCC. Among veterans without cirrhosis, hypertension (aHR, 1.63; 95% CI, 1.23-2.15; P &lt;.001) and diabetes (aHR, 1.52; 95% CI, 1.13-2.05; P = .005) were also associated with HCC. Early smoking and alcohol use were significant risk factors for HCC.Conclusions and RelevanceIn this large nationwide cohort study of Vietnam veterans, AO exposure was not associated with HCC. Smoking, alcohol, viral hepatitis, and NAFLD were the most important clinical risk factors for HCC.

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Agent Orange exposure and cancer incidence in Korean Vietnam veterans: A prospective cohort study

Cited by 42 publications

References 35 publications

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

A critical review of the epidemiology of Agent Orange or 2,3,7,8-tetrachlorodibenzo-p-dioxin and lymphoid malignancies

Exposure to Agent Orange and Risk of Bladder Cancer Among US Veterans

Exposure to Agent Orange and Hepatocellular Carcinoma Among US Military Personnel

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