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1.
Acta Oncol ; 63: 373-378, 2024 May 23.
Artículo en Inglés | MEDLINE | ID: mdl-38779869

RESUMEN

BACKGROUND: The US government considers veterans to have been exposed to Agent Orange if they served in Vietnam while the carcinogen was in use, and these veterans are often deemed at high risk of prostate cancer (PCa). Here, we assess whether presumed Agent Orange exposure is independently associated with increased risk of any metastatic or fatal PCa in a diverse Veteran cohort still alive in the modern era (at least 2011), when accounting for race/ethnicity, family history, and genetic risk. PATIENTS AND METHODS: Participants in the Million Veteran Program (MVP; enrollment began in 2011) who were on active duty during the Vietnam War era (August 1964-April 1975) were included (n = 301,470). Agent Orange exposure was determined using the US government definition. Genetic risk was assessed via a validated polygenic hazard score. Associations with age at diagnosis of any PCa, metastatic PCa, and death from PCa were assessed via Cox proportional hazards models. RESULTS AND INTERPRETATION: On univariable analysis, exposure to Agent Orange was not associated with increased PCa (hazard ratio [HR]: 1.02, 95% confidence interval [CI]: 1.00-1.04, p = 0.06), metastatic PCa (HR: 0.98, 95% CI: 0.91-1.05, p = 0.55), or fatal PCa (HR: 0.94, 95% CI: 0.79-1.09, p = 0.41). When accounting for race/ethnicity and family history, Agent Orange exposure was independently associated with slightly increased risk of PCa (HR: 1.06, 95% CI: 1.04-1.09, <10-6) but not with metastatic PCa (HR: 1.07, 95% CI: 0.98-1.15, p = 0.10) or PCa death (HR: 1.02, 95% CI: 0.83-1.23, p = 0.09). Similar results were found when accounting for genetic risk. Agent Orange exposure history may not improve modern PCa risk stratification.


Asunto(s)
Agente Naranja , Neoplasias de la Próstata , Veteranos , Guerra de Vietnam , Humanos , Masculino , Neoplasias de la Próstata/epidemiología , Neoplasias de la Próstata/mortalidad , Veteranos/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Estados Unidos/epidemiología , Defoliantes Químicos/efectos adversos , Factores de Riesgo , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/toxicidad , Dibenzodioxinas Policloradas/efectos adversos
2.
J Thorac Cardiovasc Surg ; 167(5): 1591-1600.e2, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37709166

RESUMEN

OBJECTIVE: Approximately 3 million Americans served in the armed forces during the Vietnam War. Veterans have a higher incidence rate of lung cancer compared with the general population, which may be related to exposures sustained during service. Agent Orange, one of the tactical herbicides used by the armed forces as a means of destroying crops and clearing vegetation, has been linked to the development of several cancers including non-small cell lung cancer. However, traditional risk models of lung cancer survival and recurrence often do not include such exposures. We aimed to examine the relationship between Agent Orange exposure and overall survival and disease recurrence for surgically treated stage I non-small cell lung cancer. METHODS: We performed a retrospective cohort study using a uniquely compiled dataset of US Veterans with pathologic I non-small cell lung cancer. We included adult patients who served in the Vietnam War and underwent surgical resection between 2010 and 2016. Our 2 comparison groups included those with identified Agent Orange exposure and those who were unexposed. We used multivariable Cox proportional hazards and Fine and Gray competing risk analyses to examine overall survival and disease recurrence for patients with pathologic stage I disease, respectively. RESULTS: A total of 3958 Vietnam Veterans with pathologic stage I disease were identified (994 who had Agent Orange exposure and 2964 who were unexposed). Those who had Agent Orange exposure were more likely to be male, to be White, and to live a further distance from their treatment facility (P < .05). Tumor size distribution, grade, and histology were similar between cohorts. Multivariable Cox proportional hazards modeling identified similar overall survival between cohorts (Agent Orange exposure hazard ratio, 0.97; 95% CI, 0.86-1.09). Patients who had Agent Orange exposure had a 19% increased risk of disease recurrence (hazard ratio, 1.19; 95% CI, 1.02-1.40). CONCLUSIONS: Veterans with known Agent Orange exposure who undergo surgical treatment for stage I non-small cell lung cancer have an approximately 20% increased risk of disease recurrence compared with their nonexposed counterparts. Agent Orange exposure should be taken into consideration when determining treatment and surveillance regimens for Veteran patients.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Dibenzodioxinas Policloradas , Veteranos , Adulto , Humanos , Masculino , Estados Unidos/epidemiología , Femenino , Agente Naranja , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/análisis , Estudios Retrospectivos , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4,5-Triclorofenoxiacético/análisis , Dibenzodioxinas Policloradas/efectos adversos , Dibenzodioxinas Policloradas/análisis , Neoplasias Pulmonares/inducido químicamente , Neoplasias Pulmonares/cirugía , Recurrencia Local de Neoplasia/epidemiología
3.
JAMA Netw Open ; 6(6): e2320593, 2023 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-37368398

RESUMEN

Importance: To 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. Objective: To examine the association between bladder cancer risk and exposure to Agent Orange among male Vietnam veterans. Design, Setting, and Participants: This 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. Exposure: Agent Orange. Main Outcomes and Measures: Veterans 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. Results: Among 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 Relevance: In 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.


Asunto(s)
Dibenzodioxinas Policloradas , Neoplasias de la Vejiga Urinaria , Veteranos , Masculino , Humanos , Persona de Mediana Edad , Agente Naranja , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Estudios Retrospectivos , Estudios de Cohortes , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Dibenzodioxinas Policloradas/efectos adversos , Neoplasias de la Vejiga Urinaria/inducido químicamente , Neoplasias de la Vejiga Urinaria/epidemiología
4.
Reprod Toxicol ; 119: 108413, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37236408

RESUMEN

Analyses were conducted of reproductive outcomes for conceptions of participants of the Air Force Heath Study. Participants were male Air Force veterans of the Vietnam War. Conceptions were categorized into conceived before and after the start of the participant's Vietnam War service. Analyses accounted for correlation between outcomes for multiple conceptions for each participant. For each of three non-sparsely occurring outcomes, including not live born, miscarriage, and preterm, the probability of occurrence increased substantially when conceived after compared to before the start of Vietnam War service. These results support the conclusion of an adverse effect due to Vietnam War service on these reproductive outcomes. Data for conceptions after the start of Vietnam War service for participants with measured dioxin values were used to estimate dose-response curves for the effect of dioxin exposure on the occurrence of each of the three non-sparsely occurring outcomes. These curves were assumed to be constant up to a threshold and then monotonic after that threshold. For each of the three non-sparsely occurring outcomes, the estimated dose-response curves increased nonlinearly after associated thresholds. These results support the conclusion that the adverse effect due to conception after the start of Vietnam War service is attributable to high enough exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War. Sensitivity analyses supported the conclusion that dioxin results were not substantially affected by the assumption of monotonicity, decay due to elapsed time from exposure to measurement, and available covariates.


Asunto(s)
Defoliantes Químicos , Dioxinas , Dibenzodioxinas Policloradas , Recién Nacido , Humanos , Masculino , Femenino , Ácido 2,4-Diclorofenoxiacético , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Defoliantes Químicos/efectos adversos , Defoliantes Químicos/análisis , Exposición a Riesgos Ambientales , Dibenzodioxinas Policloradas/toxicidad
5.
Reprod Toxicol ; 117: 108355, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36813141

RESUMEN

Analyses were conducted of the occurrence of eight general categories of birth defects and developmental disabilities for children fathered by participants of the Air Force Heath Study (AFHS). Participants were male Air Force veterans of the Vietnam War. Children were categorized into conceived before and after the start of the participant's Vietnam War service. Analyses accounted for correlation between outcomes for multiple children fathered by each of the participants. For each of the eight general categories of birth defects and developmental disabilities, the probability of its occurrence increased substantially for children conceived after compared to before the start of Vietnam War service. These results support the conclusion of an adverse effect on reproductive outcomes due to Vietnam War service. Data for children conceived after the start of Vietnam War service for participants with measured dioxin values were used to estimate dose-response curves for the effect of dioxin exposure on the occurrence of each of the eight general categories of birth defects and developmental disabilities. These curves were assumed to be constant up to a threshold and then monotonic after that threshold. For seven of the eight general categories of birth defects and developmental disabilities, the estimated dose-response curves increased nonlinearly after associated thresholds. These results support the conclusion that the adverse effect to conception after the start of Vietnam War service may be attributable to high enough exposures to dioxin, a toxic contaminant of Agent Orange used for herbicide spraying in the Vietnam War.


Asunto(s)
Dioxinas , Dibenzodioxinas Policloradas , Humanos , Masculino , Niño , Femenino , Ácido 2,4-Diclorofenoxiacético , Discapacidades del Desarrollo/epidemiología , Discapacidades del Desarrollo/inducido químicamente , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Agente Naranja , Exposición a Riesgos Ambientales
6.
Am J Respir Crit Care Med ; 206(6): 750-757, 2022 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-35559726

RESUMEN

Rationale: There is limited literature exploring the relationship between military exposures and idiopathic pulmonary fibrosis (IPF). Objectives: To evaluate whether exposure to Agent Orange is associated with an increased risk of IPF among veterans. Methods: We used Veterans Health Administration data to identify patients diagnosed with IPF between 2010 and 2019. We restricted the cohort to male Vietnam veterans and performed multivariate logistic regression to examine the association between presumptive Agent Orange exposure and IPF. We conducted sensitivity analyses restricting the cohort to army veterans (highest theoretical burden of exposure, surrogate for dose response) and a more specific case definition of IPF. Fine-Gray competing risk models were used to evaluate age to IPF diagnosis. Measurements and Main Results: Among 3.6 million male Vietnam veterans, 948,103 (26%) had presumptive Agent Orange exposure. IPF occurred in 2.2% of veterans with Agent Orange exposure versus 1.9% without exposure (odds ratio, 1.14; 95% confidence interval [CI], 1.12-1.16; P < 0.001). The relationship persisted after adjusting for known IPF risk factors (odds ratio, 1.08; 95% CI, 1.06-1.10; P < 0.001). The attributable risk among exposed veterans was 7% (95% CI, 5.3-8.7%; P < 0.001). Numerically greater risk was observed when restricting the cohort to 1) Vietnam veterans who served in the army and 2) a more specific definition of IPF. After accounting for the competing risk of death, veterans with Agent Orange exposure were still more likely to develop IPF. Conclusions: Presumptive Agent Orange exposure is associated with greater risk of IPF. Future research should validate this association and investigate the biological mechanisms involved.


Asunto(s)
Fibrosis Pulmonar Idiopática , Dibenzodioxinas Policloradas , Veteranos , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Agente Naranja , Humanos , Fibrosis Pulmonar Idiopática/epidemiología , Masculino , Dibenzodioxinas Policloradas/toxicidad
7.
Leuk Lymphoma ; 63(7): 1534-1543, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35105250

RESUMEN

Agent Orange (AO) was the dominant weaponized herbicide employed by the United States (US) military during the Vietnam war. AO, however, was found to be regularly contaminated by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic dioxin known; furthermore, AO was commonly diluted in the field with other aromatic hydrocarbons to assist with delivery mechanisms. Unbeknownst to the US military and the millions exposed, these events have likely contributed to the development of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) that has affected many veterans. Null studies regarding an association between AO exposure and AML/MDS are limited in their methodology and application. The acknowledgement that the known carcinogen TCDD was a contaminant in AO when paired with a strong biological plausibility for its leukemogenicity and an observed increased risk of AML/MDS in TCDD-exposed individuals should suffice to establish causal association and that veterans to whom this might apply should be awarded appropriate indemnity.


Asunto(s)
Dioxinas , Leucemia Mieloide , Dibenzodioxinas Policloradas , Veteranos , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/toxicidad , Agente Naranja , Dioxinas/toxicidad , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/análisis , Humanos , Dibenzodioxinas Policloradas/análisis , Dibenzodioxinas Policloradas/toxicidad , Estados Unidos
8.
Med Confl Surviv ; 32(2): 138-152, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27748632

RESUMEN

Attempts through the US courts to hold the corporations responsible for the production of dioxin-contaminated herbicides used by the US military in the 1960s and early 1970s liable for their ongoing health consequences have failed. This article scrutinizes the most recent judgement - that of the United States District Court for the Eastern District of New York handed down in 2005 following a lawsuit brought by the Vietnam Association of Victims of Agent Orange/dioxin (VAVA). It is argued that despite this judgement there is the potential to bring a further legal case, with some prospect of success, on the basis of: (i) debatable legal judgements in the 2005 decision; (ii) new scientific evidence on the health effects of exposure to Agent Orange; and (iii) cases brought in other jurisdictions. The article concludes by noting the underfunding of ongoing remediation efforts, especially for the provision of assistance to affected individuals, and argues that it is desirable to oblige the producers of the herbicides to contribute financially to these efforts.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Industria Química/legislación & jurisprudencia , Defoliantes Químicos/efectos adversos , Responsabilidad Legal , Dibenzodioxinas Policloradas/efectos adversos , Agente Naranja , Causalidad , Humanos , Derecho Internacional , Estados Unidos , Veteranos/legislación & jurisprudencia , Guerra de Vietnam
9.
J Am Acad Dermatol ; 74(1): 143-70, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26210237

RESUMEN

Organochlorine exposure is an important cause of cutaneous and systemic toxicity. Exposure has been associated with industrial accidents, intentional poisoning, and the use of defoliants, such as Agent Orange in the Vietnam War. Although long-term health effects are systematically reviewed by the Institute of Medicine, skin diseases are not comprehensively assessed. This represents an important practice gap as patients can present with cutaneous findings. This article provides a systematic review of the cutaneous manifestations of known mass organochlorine exposures in military and industrial settings with the goal of providing clinically useful recommendations for dermatologists seeing patients inquiring about organochlorine effects. Patients with a new diagnosis of chloracne, porphyria cutanea tarda, cutaneous lymphomas (non-Hodgkin lymphoma), and soft-tissue sarcomas including dermatofibrosarcoma protuberans and leiomyosarcomas should be screened for a history of Vietnam service or industrial exposure. Inconclusive evidence exists for an increased risk of other skin diseases in Vietnam veterans exposed to Agent Orange including benign fatty tumors, melanomas, nonmelanoma skin cancers, milia, eczema, dyschromias, disturbance of skin sensation, and rashes not otherwise specified. Affected veterans should be informed of the uncertain data in those cases. Referral to Department of Veterans Affairs for disability assessment is indicated for conditions with established associations.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Hidrocarburos Clorados/efectos adversos , Personal Militar , Dibenzodioxinas Policloradas/efectos adversos , Enfermedades de la Piel/inducido químicamente , Agente Naranja , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Medición de Riesgo , Enfermedades de la Piel/epidemiología , Enfermedades de la Piel/fisiopatología , Estados Unidos , Vietnam
11.
JAMA Oncol ; 1(8): 1061-8, 2015 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-26335650

RESUMEN

IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURES: Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Herbicidas/efectos adversos , Gammopatía Monoclonal de Relevancia Indeterminada/inducido químicamente , Mieloma Múltiple/inducido químicamente , Exposición Profesional/efectos adversos , Dibenzodioxinas Policloradas/efectos adversos , Salud de los Veteranos , Guerra de Vietnam , Anciano , Anciano de 80 o más Años , Agente Naranja , Biomarcadores/sangre , Estudios de Casos y Controles , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Gammopatía Monoclonal de Relevancia Indeterminada/sangre , Gammopatía Monoclonal de Relevancia Indeterminada/diagnóstico , Gammopatía Monoclonal de Relevancia Indeterminada/epidemiología , Mieloma Múltiple/sangre , Mieloma Múltiple/diagnóstico , Mieloma Múltiple/epidemiología , Oportunidad Relativa , Dibenzodioxinas Policloradas/sangre , Prevalencia , Estudios Prospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Estados Unidos/epidemiología
13.
Fed Regist ; 80(118): 35246-9, 2015 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-26103644

RESUMEN

The Department of Veterans Affairs (VA) is amending its regulation governing individuals presumed to have been exposed to certain herbicides. Specifically, VA is expanding the regulation to include an additional group consisting of individuals who performed service in the Air Force or Air Force Reserve under circumstances in which they had regular and repeated contact with C-123 aircraft known to have been used to spray an herbicide agent ("Agent Orange'') during the Vietnam era. In addition, the regulation will establish a presumption that members of this group who later develop an Agent Orange presumptive condition were disabled during the relevant period of service, thus establishing that this service constituted "active, naval, military or air service.'' The effect of this action is to presume herbicide exposure for these individuals and to allow individuals who were exposed to herbicides during reserve service to establish veteran status for VA purposes and eligibility for some VA benefits. The need for this action results from a recent decision by the Secretary of Veterans Affairs to acknowledge that individuals who had regular and repeated exposure to C-123 aircraft that the United States Air Force used to spray the herbicides in Vietnam during Operation Ranch Hand were exposed to Agent Orange.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Evaluación de la Discapacidad , Dibenzodioxinas Policloradas/efectos adversos , Veteranos/legislación & jurisprudencia , Agente Naranja , Personas con Discapacidad/legislación & jurisprudencia , Determinación de la Elegibilidad/legislación & jurisprudencia , Exposición a Riesgos Ambientales/efectos adversos , Herbicidas/efectos adversos , Humanos , Personal Militar/legislación & jurisprudencia , Estados Unidos , Guerra de Vietnam
14.
Urol Oncol ; 33(7): 329.e1-6, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25998746

RESUMEN

PURPOSE: To investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes. MATERIAL AND METHODS: Data from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics. RESULTS: There were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P<0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph node positivity, and extracapsular extension did not differ with AO exposure. At a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%) patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%) died of PC. On multivariable analysis, AO exposure was not associated with BCR, secondary treatment, metastases, or PC mortality. CONCLUSIONS: AO exposure was not associated with worse preoperative characteristics such as elevated prostate-specific antigen levels or biopsy GS nor with BCR, secondary treatment, metastases, or PC death. Thus, as data on AO-exposed men mature, possible differences in PC outcomes observed previously are no longer apparent.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Defoliantes Químicos/efectos adversos , Dibenzodioxinas Policloradas/efectos adversos , Prostatectomía , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/cirugía , Anciano , Agente Naranja , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Antígeno Prostático Específico/sangre , Estudios Retrospectivos , Estados Unidos , Veteranos
15.
J Pediatr ; 165(6): 1216-21, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25241182

RESUMEN

OBJECTIVE: To evaluate the role of parental military service-related exposures and rhabdomyosarcoma (RMS) risk in offspring using data from a large case-control study of childhood RMS. STUDY DESIGN: Cases (n = 319) were enrolled from the third trial run by the Intergroup Rhabdomyosarcoma Study Group. Population-based controls (n = 319) were pair-matched to cases on race, sex, and age. Conditional logistic regression was used to evaluate parental military service-related exposures and their associations with childhood RMS by generating aORs and 95% CIs. Statistical significance was defined as P < .05. RESULTS: There were no significant associations between parental military service and childhood RMS. The strongest association was with maternal military service; however, this association was attenuated and did not remain significant after adjusting for covariates (aOR = 2.75, 95% CI 0.71, 10.62). An elevated effect estimate was found when assessing paternal exposure to Agent Orange (AO) and childhood RMS but was not statistically significant (aOR = 1.72, 95% CI 0.55, 5.41). CONCLUSIONS: We found little evidence that parental military service of AO exposure influences the risk of RMS in offspring. These findings are notable in light of the continuing controversies surrounding the intergenerational effects of AO exposure.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Defoliantes Químicos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Personal Militar , Dibenzodioxinas Policloradas/efectos adversos , Efectos Tardíos de la Exposición Prenatal/epidemiología , Rabdomiosarcoma/epidemiología , Guerra de Vietnam , Adulto , Agente Naranja , Estudios de Casos y Controles , Niño , Femenino , Historia Antigua , Humanos , Masculino , Exposición Materna , Padres , Exposición Paterna , Embarazo
16.
Eur J Epidemiol ; 29(10): 667-723, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25064616

RESUMEN

To inform risk assessment and regulatory decision-making, the relationship between 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and prostate cancer requires clarification. This article systematically and critically reviews the epidemiologic evidence on the association between exposure to TCDD or Agent Orange, a TCDD-contaminated herbicide used during the Vietnam War, and prostate cancer risk. Articles evaluated include 11 studies of three cohorts, four case-control or cross-sectional studies, and three case-only studies of military veterans with information on estimated Agent Orange or TCDD exposure; 13 studies of seven cohorts, one case-control study, and eight proportionate morbidity or mortality studies of Vietnam veterans without information on Agent Orange exposure; 11 cohort studies of workers with occupational exposure to TCDD; and two studies of one community cohort with environmental exposure to TCDD. The most informative studies, including those of Vietnam veterans involved in Agent Orange spraying or other handling, herbicide manufacturing or spraying workers with occupational TCDD exposure, and community members exposed to TCDD through an industrial accident, consistently reported no significant increase in prostate cancer incidence or mortality. Only some potentially confounded studies of Vietnam veterans compared with the general population, studies with unreliable estimates of Agent Orange exposure, and analyses of selected subgroups of Vietnam veterans reported positive associations. Overall, epidemiologic research offers no consistent or convincing evidence of a causal relationship between exposure to Agent Orange or TCDD and prostate cancer. More accurate exposure assessment is needed in large epidemiologic studies to rule out a causal association more conclusively.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Exposición a Riesgos Ambientales , Dibenzodioxinas Policloradas/efectos adversos , Neoplasias de la Próstata/inducido químicamente , Neoplasias de la Próstata/epidemiología , Medición de Riesgo , Agente Naranja , Contaminantes Ambientales , Estudios Epidemiológicos , Humanos , Masculino , Personal Militar , Veteranos
17.
Leuk Lymphoma ; 55(1): 63-6, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23573826

RESUMEN

Exposure to Agent Orange (AO) and the contaminating chemical 2,3,7,8-tetrachlorodibenzodioxin (TCDD) has been associated with the development of chronic lymphocytic leukemia (CLL). Of the 195 veterans diagnosed with CLL from 2001 to 2010 in a retrospective cohort from the Minneapolis Veterans Affairs Medical Center, 33 (17%) were exposed to AO. Prognostic factors including Rai stage, lymphocyte doubling time and cytogenetics did not differ between exposed and unexposed patients. Exposed patients were younger at diagnosis (61 vs. 72 years, p < 0.0001) and time to CLL treatment was shorter (9.6 vs. 30.2 months, p = 0.02). Overall survival did not differ between exposed and unexposed patients on Kaplan-Meier analysis, but when adjusted for age, AO exposure had a hazard ratio of death of 1.8 compared to non-exposure (95% confidence interval 0.7-4.5, p = 0.24). The high estimate of the mortality hazard combined with the relatively low numbers in the exposure group suggests that further examination in a larger patient population is warranted.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Defoliantes Químicos/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Leucemia Linfocítica Crónica de Células B/epidemiología , Leucemia Linfocítica Crónica de Células B/etiología , Dibenzodioxinas Policloradas/efectos adversos , Adulto , Anciano , Anciano de 80 o más Años , Agente Naranja , Femenino , Estudios de Seguimiento , Humanos , Leucemia Linfocítica Crónica de Células B/mortalidad , Leucemia Linfocítica Crónica de Células B/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Veteranos
19.
Prostate Cancer Prostatic Dis ; 16(4): 376-81, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24018710

RESUMEN

BACKGROUND: Agent Orange (AO) was previously identified as a significant risk factor for biochemical recurrence (BCR) after radical prostatectomy (RP) in prostate cancer patients. In this study, we determined the levels of dioxin biological toxicity using toxic equivalency (TEQ) values and examined the impact of dioxin-TEQ level on BCR. METHODS: A total of 93 men who underwent RP, with a median of 5.3 years of postoperative follow-up, were included in the study. The dioxin-TEQ level of each patient was measured using intraoperatively harvested abdominal subcutaneous fat. The dichotomous categorization of dioxin-TEQ by the 50th percentile (low<50% vs high 50%) was also used to regroup the patient cohort, regardless of the previous history of AO exposure. Comparisons between the dioxin-TEQ levels, clinicopathological characteristics and BCR in AO-exposed and -unexposed men were made to allocate possible risk factors. The multivariable logistic regression model was used to identify significant risk factors associated with BCR, adjusting for other confounding factors. RESULTS: The median dioxin-TEQ level in 37 AO-exposed patients was significantly higher than that in 56 unexposed patients (22.3 vs 15.0 pg g(-1) fat, respectively, P<0.001). The men with AO exposure were more likely to have a high dioxin-TEQ level (P<0.001). Neither AO exposure nor the level of dioxin-TEQ was associated with BCR. Tumor stage (T3/T4 vs T2) and Gleason grade (Gleason 3+4) were independent risk factors for BCR after RP. CONCLUSIONS: Exposure to AO significantly increases the adipose level of dioxin-TEQ in patients treated with RP. However, exposure to AO or a high dioxin-TEQ level was not associated with an increased risk of BCR after RP. This lack of association supports the current conclusion that the evidence of carcinogenicity of AO in prostate cancer patients is not sufficient and remains 'limited'.


Asunto(s)
Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Dioxinas/efectos adversos , Dibenzodioxinas Policloradas/efectos adversos , Neoplasias de la Próstata/etiología , Neoplasias de la Próstata/patología , Ácido 2,4,5-Triclorofenoxiacético/química , Ácido 2,4-Diclorofenoxiacético/química , Agente Naranja , Biopsia , Dioxinas/química , Exposición a Riesgos Ambientales/efectos adversos , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Dibenzodioxinas Policloradas/química , Próstata/efectos de los fármacos , Próstata/patología , Próstata/cirugía , Antígeno Prostático Específico/sangre , Prostatectomía , Neoplasias de la Próstata/cirugía , Factores de Riesgo , Factores de Tiempo
20.
Fed Regist ; 78(173): 54763-6, 2013 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-24040683

RESUMEN

The Department of Veterans Affairs (VA) adopts as a final rule its proposal to amend its adjudication regulations by clarifying and expanding the terminology regarding presumptive service connection for acute and subacute peripheral neuropathy associated with exposure to certain herbicide agents. This amendment implements a decision by the Secretary of Veterans Affairs based on findings from the National Academy of Sciences (NAS) Institute of Medicine report, Veterans and Agent Orange: Update 2010. It also amends VA's regulation governing retroactive awards for certain diseases associated with herbicide exposure as required by court orders in the class action litigation of Nehmer v. U.S. Department of Veterans Affairs.


Asunto(s)
Evaluación de la Discapacidad , Herbicidas/efectos adversos , Enfermedades del Sistema Nervioso Periférico/etiología , Veteranos/legislación & jurisprudencia , Ácido 2,4,5-Triclorofenoxiacético/efectos adversos , Ácido 2,4-Diclorofenoxiacético/efectos adversos , Causalidad , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Dibenzodioxinas Policloradas/efectos adversos , Estados Unidos , Guerra de Vietnam
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