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Veterans and Agent Orange: Update 2012 (2014)

Chapter: 5 Epidemiologic Studies: Compendium of New Publications

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Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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5


Epidemiologic Studies: Compendium of New Publications

The continuing effort to evaluate and integrate epidemiologic studies pertinent to possible health effects of the chemicals of interest (COIs)—2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 4-amino-3,5,6-trichloropicolinic acid (picloram), and dimethylarsinic acid (DMA or cacodylic acid)—has involved the review of thousands of publications over successive reports (the original retrospective report, eight updates prior to the current report, and three short reports on single issues, as delineated in the second and third paragraphs of Chapter 1). The search strategy used to identify these publications is described starting on the first page of Chapter 2, along with explanations of various refinements that have been employed since the initial volume in this series was prepared.

The first part of this chapter tabulates publications of primary epidemiologic research that appeared in the period from October 1, 2010 (the closing date for inclusion in Update 2010 [IOM, 2011]), through September 30, 2012, as a compendium of new information on human health outcomes considered by the present committee. In this chapter and later chapters, epidemiologic studies are organized into categories according to the populations being studied (Vietnam veterans, occupational populations other than Vietnam veterans, and nonoccupational populations affected by environmental exposures) or by study design (case-control). The various study designs (most important, cohort, case-control, and cross-sectional) have strengths and weaknesses that influence their potential to contribute evidence considered in the health-outcomes chapters.

The second part of this chapter provides design information on populations that are the subject of multiple references in this and earlier Veterans and

Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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Agent Orange (VAO) reviews—including new studies of populations that have been studied previously and studies of new populations that had multiple health outcomes—to avoid repeating design information in multiple health-outcomes chapters. (Design information on studies of new populations that involve single health outcomes is provided in the various health-outcomes chapters.) For presentation of the background information, the study populations are arranged into categories on the basis of whether they are composed of Vietnam veterans, occupationally exposed workers, or environmentally exposed individuals or were assembled according to a case-control approach focused on particular health outcomes.

In addition to reviewing studies involving exposures to the specific COIs listed previously, this and earlier VAO committees have considered studies that examined compounds chemically related to the herbicides used in Vietnam, such as 2-(2-methyl-4-chlorophenoxy) propionic acid, hexachlorophene, and chlorophenols, particularly 2,4,5-trichlorophenol. Some publications did not indicate the specific herbicides to which study participants were exposed or the magnitude of exposure; those limitations were considered when the committee weighed the relevance of each publication, as detailed in Chapter 2. The committee also considers studies of exposure to polychlorinated biphenyls and other dioxin-like compounds (DLCs) informative if their results were reported in terms of TCDD toxic equivalents (TEQs) or concentrations of specific congeners of DLCs. Available details of exposure assessment and use of the resulting data in analyses are discussed in Chapter 3, which follows the same sequence to categorize study populations.

NEW EPIDEMIOLOGIC PUBLICATIONS

The new epidemiologic publications reviewed by the committee for this update are listed in Tables 5-1, 5-2, and 5-3. The conditions listed in the “Health Outcomes Reported” columns are indicative of the chapters in which the new publications are considered. Note, however, that studies assessing the occurrence of various cancers after exposure scenarios temporally comparable with exposure during military service are discussed in Chapter 8, which addresses cancer outcomes as applicable to the veterans themselves. Studies of childhood cancers in relation to parental exposure to the COIs are discussed in Chapter 10, which addresses possible adverse effects in veterans’ offspring. Cancer studies that consider only childhood exposure are not considered relevant to the committee’s charge.

Publications Reporting a Single Health Outcome in New Populations

New publications reporting a single health outcome in populations not studied previously are listed in Table 5-1, with an indication of the outcomes. De-

Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

TABLE 5-1 Publications Reporting a Single Health Outcome in New Populations

Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Studies of Vietnam Veterans
None
Occupational Studies
Kamel et al., 2012 Case-control (nested) Pesticides, herbicides, 2,4-D, 2,4,5-T, dicamba ALS AHS
Environmental Studies
Buck Louis et al., 2011 Cross-sectional anti-estrogenic PCBs (correspond to dl PCBs) Menstrual cycles Women without reproductive problems
Goncharov et al., 2011 Cross-sectional PCB subsets (mono-ortho TEQ, estrogenic) Hypertension Anniston (AL) Community Health Survey
Kezios et al., 2012 Pregnancy cohort dl PCB 118 Birth weight, gestational age California Child Health and Development Studies, University of California, Berkeley
Leijs et al., 2012 Prospective cohort Prenatal TEQs for dioxin/furans, dl PCBs Sons’ thyroid metabolism at puberty Mother–baby pairs from Netherlands (followup on cohort of Ilsen et al., 1996)
Miyashita et al., 2011 Cohort Total dioxins, furans, dl PCBs (non-ortho and mono-ortho) in maternal blood (3rd trimester) Immune function in offspring (infections [otitis media], allergies [asthma, eczema, food allergies]) Hokkaido Study on Environment and Children’s Health Japanese mothers and infants examined at birth and at 18 months of age
Nishijo et al., 2012 Birth cohort TEQs PCDD/Fs in breast milk 1 mo after birth Infant growth (birth, 1 mo, 4 mo), neurodevelopment Mother–infant pairs from contaminated area of Vietnam
Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Virtanen et al., 2012; Krysiak-Baltyn et al., 2012 Case-control (nested) TEQs for dioxins, furans, PCBs in placenta, individual results on comprehensive list of dl-PCBs; in breast milk Congenital cryptorchidism; Seeking pattern of congeners distinguishing cases with cryptorchidism form controls [results of interest in Virtanen et al., 2012] Danish-Finnish Prospective Cohort: boys examined at birth and 3 months of age
Case-Control Studies
Band et al., 2011 Case-control 2,4-D, MCPA, dicamba Prostate cancer British Columbia farmers
Bonefeld-Jorgensen et al., 2011 Case-control Sum dl PCBs, AHR-TEQs Breast cancer Inuit women from Greenland sampled 2000–2003
Cai et al., 2011 Case-control Dioxins, furans, all dl-PCBs, TEQ in peritoneal fluid and serum Endometriosis Japanese women undergoing diagnostic laparoscopy for infertility enrolled from October 2004 to March 2007
Gallagher et al., 2011 Case-control dl PCBs 118, 156, total dl PCBs in serum Melanoma Study participants were recruited using a population-based British Columbia Cancer Registry
Lv et al., 2011 Case-control Occupational exposure to herbicides [marginal] MDS Shanghai, China
Postuma et al., 2012 Case-control Occupational herbicide exposure, non-occupational only as specific as “pesticides” [marginal] REM sleep behavior disorder (prognostic sign of PD and dementia) Cases drawn from seven centers
Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Rollison et al., 2011 Case-control Pesticides, herbicides (case-control comparison shown for telomere length and then telomere length within MDS cases compared on basis of pesticide use) [marginal] MDS (indirect evidence) Newly diagnosed MDS cases in Florida
Rugbjerg et al., 2011 Case-control Self-reported pesticide exposure (2,4-D & 2,4,5-T in “herbicides,” “pesticides with known neurotoxicity” classes) [marginal] PD British Columbia PD cases and controls
Slater et al., 2011 Case-control Household chemicals (specificity to level of “herbicides”) [marginal] Leukemia in infants Infants diagnosed with acute leukemia at < 1 year of age at Children’s Oncology Group institutions in US and Canada
Wong et al., 2010 Case-control Primarily job title, but also “herbicides” [marginal] NHL Newly diagnosed patients in Shanghai
Zakerinia et al., 2012 Case-control Pesticides [for individual types]; Herbicides for all lymphomas Lymphoid neoplasms (HL, NHL, multiple myeloma, T-cell) Diagnoses at Nemazee Hospital, Shiraz, Iran

NOTE: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; AHR, aryl hydrocarbon receptor; AHS, Agricultural Health Study; ALS, amyotrophic lateral sclerosis; dl, dioxin-like; HL, Hodgkin lymphoma; MCPA, 2-methyl-4-chlorophenoxyacetic acid; MDS, myelodysplastic syndrome; NHL, non-Hodgkin lymphoma; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDF, polychlorinated dibenzofuran; REM, rapid eye movement; TEQ, total toxic equivalent.

scriptions and critiques of the designs of the studies are provided in the sections of the report that discuss the results related to particular health outcomes. The publications in this table are predominantly case-control studies, where the focus of the investigation is on a particular health outcome.

Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

Publications Reporting Multiple Health Outcomes in New Populations

New publications reporting multiple health outcomes in populations not studied previously are listed in Table 5-2, with a list of outcomes that were investigated. Comprehensive discussions of the designs of the studies are presented in Chapter 6, organized according to the type of study population. The results, with comments related to their reliability or limitations, appear in the appropriate outcome-specific sections of Chapters 713.

New Publications on Previously Studied Populations

The new publications on previously studied populations are listed in Table 5-3. The new publications are reviewed in the context of the history of publications on the same populations to take into account the fact that they are not presenting entirely new evidence but rather enhancing a picture that has been emerging for many years.

A number of long-term studies of populations exposed to the COIs are of particular importance to the VAO project. The disease experiences of those populations are updated with the passage of time. Placing each new publication into its historical context helps the committee to combine the evidence from various publications appropriately and to take into consideration the interdependence of related publications. Such clusters of studies are useful in describing the course of a population’s response to an exposure, and joint consideration of an entire body of research on a population may yield insight into relationships with potential confounding factors.

Many groups potentially exposed to the COIs have been monitored periodically, including the cohorts of the International Agency for Research on Cancer (IARC) and the National Institute for Occupational Safety and Health (NIOSH); residents of Seveso; and Operation Ranch Hand and Army Chemical Corps personnel. For the sake of completeness, the discussions of specific health outcomes and the associated cumulative-results tables in Chapters 713 include references to publications discussed in previous VAO reports and to new publications. In drawing its conclusions, the committee combined the evidence in new publications and the evidence synthesized in the most recent update (Update 2010), taking into account the interdependence of related publications.

Individual researchers who belong to research consortia that are evaluating cohorts in large multicenter studies (such as the IARC and NIOSH cohort studies) sometimes publish reports based on the subsets of study participants that they themselves are monitoring. The VAO committees take into consideration all reports that have been published, including those based on entire cohorts and those based on subcohorts. In drawing its conclusions, the committee factored in both types of studies, taking into consideration the interdependence among related studies. In particular, some subcohort studies have access to information

Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

TABLE 5-2 Publications on Multiple Health Outcomes in New Study Populations

Citation Study Design Exposure Measures(s) Having Results Health Outcome(s) Reported Study Population
Studies of Vietnam Veterans
Kim JB et al., 2012 Case-control TCDD HT, hyperlipidemia, clinical outcomes (rate and severity of major adverse coronary events) Korean VV (50–70 yrs of age undergoing angiograms for acute coronary syndrome)
Occupational Studies
None
Environmental Studies
Chang et al., 2011a Cross-sectional Serum PCDD/F TEQ Insulin resistance Taiwan, 1,449 nondiabetic residents around closed PCP factory
Chang et al., 2011b Cross-sectional Serum PCDD/F TEQ CVD Taiwan, 914 residents without CVD around closed PCP factory
Chang et al., 2012 Cross-sectional Serum PCDD/F TEQ, also consideration of diet as source Blood chemistries [Indirect evidence—more like biologic plausibility] Taiwan, workers from closed PCP factory vs residents vs general population
Lee et al., 2010 Nested case-control dl-PCBs 105, 118, 156, 157, 167 in serum Diabetes CARDIA cohort
Lee et al., 2011a Nested case-control dl-PCBs 105, 118, 156, 157, 167 in serum Obesity, dyslipedemia, insulin resistance CARDIA cohort participants; study subjects recruited at baseline in 1985–1986 and followed for 20 yrs
Lee et al. 2011b Cross-sectional and prospective dl-PCBs 105, 118, 156, 157, 189 in serum Diabetes PIVUS (men and women analyzed together)
Lee et al., 2012a Cross-sectional and prospective dl-PCBs 105, 118, 126, 156, 157, 169, 189 in serum Abdominal obesity PIVUS (men and women analyzed separately)
Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Citation Study Design Exposure Measures(s) Having Results Health Outcome(s) Reported Study Population
Lee et al., 2012b Cross-sectional and prospective dl-PCBs 105, 118, 126, 156, 157, 169, 189 in serum stroke PIVUS (men and women analyzed separately)
Lind et al., 2012 Cross-sectional and prospective Circulating POPs (dl PCBs 105, 118, 126, 156, 157, 169, 189) Atherosclerosis (carotid artery plaques, intima-media thickness, gray scale of median) PIVUS study
Rönn et al., 2011 Cross-sectional, prospective dl-PCBs 105, 118, 123, 169, 156, 157, 189 in serum Fat mass, obesity PIVUS study participants; Uppsala elderly
Silverstone et al., 2012 Cross-sectional PCB subsets (mono-ortho TEQ, estrogenic) Diabetes Anniston (Alabama) Community Health Survey
Stolevik et al., 2011 Prospective cohort Prenatal exposure, TEQs for all dioxins, furans, dl PCBs (estimated from mothers’ food frequency questionnaire) Infection, eczema, wheeze Birth cohort from Norwegian Mother and Child Cohort Study (MoBa)
Case-Control Studies
Rocheleau et al., 2011 Case-control maternal occupational herbicides expo, 1 mo before conception, 1st trimester, or 2nd–3rd trimester Hypospadias National Birth Defects Prevention Study (NBDPS)

NOTE: AO, Agent Orange; CARDIA, Coronary Artery Risk Development in Young Adults cohort; CVD, cardiovascular disease; dl, dioxin-like; HT, hypertension; NBDPS, National Birth Defects Prevention Study; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDF, polychlorinated dibenzofuran; PCP, pentachlorophenol; PIVUS, Prospective Investigation of the Vasculature in Uppsala Seniors; POP, persistant organic pollutant; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TEQ, total toxic equivalent; VV, Vietnam veteran.

Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

TABLE 5-3 Publications on Previously Studied Populations

Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Studies of Vietnam Veterans
None
Occupational Studies
Andreotti et al., 2010 Cohort Dicamba and BMI as factors for colon cancer [marginal] Focus on BMI at enrollment and incidence of various cancers [not relevant] Colon cancer from interaction of dicamba and BMI AHS (licensed pesticide applicators and spouses)
Boers et al., 2012 Cohort Chlorophenoxy herbicides (plasma TCDD) All cancers and specific (stomach, pancreas, trachea/ bronchus/lung, melanoma, genital, prostate, bladder, kidney, NHL, leukemia), and IHD Subcohort of IARC cohort (Netherlands) [followup to 2006 like Boers et al. (2010)]
Burns et al., 2011 Cohort 2,4-D Cancer incidence (1985–2007) from all cancer and full spectrum individually Subcohort of NIOSH (Dow Chemical, Midland, Michigan plant workers)
Kenborg et al., 2012 Cohort Pesticide exposure mainly to herbicides (including phenoxys) [marginal] Incidence PD and smoking-related cancers (lung, larynx, bladder) Danish Union of Gardeners
Koutros et al., 2010a Cohort Pesticides [2,4-D known to be among most frequently used herbicides] [marginal] Cancer incidence (extended through 2006) from all cancers and full spectrum individually AHS (licensed pesticide applicators: private, commercial and spouses)
Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Koutros et al., 2010b, 2011; Barry et al., 2011, 2012 Nested case-control 2,4,5-T; 2,4-D; 2,4,5-TP; dicamba Prostate cancer incidence 1993–2003 [most complete dose response info in Koutros et al., 2011] AHS (licensed pesticide applicators); interaction between pesticide use and SNPs (in metabolic DNA repair, and 8q24 genes) for prostate cancer risk
Manuwald et al., 2012 Cohort Cumulative TCDD exposure estimated from tissue samples and job history All cancers and full spectrum individually German production workers at Hamburg plant (IARC)
Ruder and Yiin, 2011 Cohort PCP (subgroups with and without exposure to TCDD in addition) Mortality (to 2005) (full spectrum) US PCP workers (NIOSH)
Saberi Hosnijeh et al., 2011 Cohort 2,4-D, 2,4,5-T, 2,4,5-TCP, MCPA, MCPP Humoral immunity (C-4, associated with NHL), atopic disease (asthma) Subcohort of IARC (Dutch phenoxy herbicide workers)
Saberi Hosnijeh et al., 2012 Cohort 2,4-D, 2,4,5-T, 2,4,5-TCP, MCPA, MCPP Plasma cytokine concentrations (possible suppression of immunity) Subcohort of IARC (Dutch phenoxy herbicide workers)
Waggoner et al., 2011 Cohort Pesticides (2,4-D known to be among most frequently used herbicides) [marginal] Mortality (1993–2007) (includes full spectrum of individual cancers; diabetes mellitus; and diseases of systems related to respiration, digestion, bone and connective tissue, heart and circulation) AHS (licensed pesticide applicators and spouses)
Environmental Studies
Cho et al., 2011 Cross-sectional DLCs (PCB 126, hpCDD, OCDD) Bone mineral density, fat mass NHANES (1999–2004)
Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Humblet et al., 2011 Cohort Dioxin, PCB concentrations in maternal blood (TEQs) Pubertal onset Mother–son pairs from Chapaevsk, Russia
Jones et al., 2011 Cross-sectional Urinary arsenic Hypertension NHANES (2003–2008)
Lambertino et al., 2011 Cohort Σdl PCBs Uterine leiomyoma Great Lakes Fish Consumption Study
Mocarelli et al., 2011 Cohort Serum concentrations of TCDD Sperm quality and reproductive hormones in offspring Seveso; sons born (1977–1984) to dioxin-exposed mothers
Su et al., 2012 Cohort TEQs for PCBs, PCDD/Fs Reproductive development Taiwanese Mother- and-Child Study; followup to 8 yrs of age
Tsukimori et al., 2012b Cohort Dioxin, furan, and PCB TEQs in maternal blood extrapolated back to delivery Birth weight (by sex of infant) Yusho mothers and children
Warner et al., 2011 Cohort Serum concentrations of TCDD Breast cancer SWHS (Seveso women 0–40 yrs old at time of accident; followup through 2008)
Case-Control Studies
Hohenadel et al., 2011 Case-control Herbicides, phenoxys, 2,4-D alone and in combination with malathion NHL Cross-Canada Study of Pesticides and Health
Karunanayake et al., 2012 Case-control ≥ 10 hr/yr pesticide expo (2,4-D, Mecoprop, MCPA, Diclofomethyl, and dicamba) Hodgkin Lymphoma Cross-Canada Study of Pesticides and Health
Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×
Citation Study Design Exposure Measure(s) Having Results Health Outcome(s) Reported Study Population
Pahwa et al., 2011 Case-control Pesticide use (results on all phenoxys, 2,4-D, Mecoprop, MCPA, Diclofop-methyl) STS Cross-Canada Study of Pesticides and Health
Viel et al., 2011 Case-control TEQs for dioxins, furans, and dl PCBs NHL NHL cases using population-based cancer registry, living in vicinity of a solid-waste incinerator in France
Yiin et al., 2012 Case-control Quantified pesticide exposure (phenoxys, 2,4-D, dicamba) Gliomas UMHS (pesticide applicators)

NOTE: 2,4-D, 2,4-dichlorophenoxyacetic acid; 2,4,5-T, 2,4,5-trichlorophenoxyacetic acid; 2,4,5-TCP, 2,4,5-trichlorophenol; 2,4,5-TP, 2-(2,4,5-trichlorophenoxy) propionic acid; AHS, Agricultural Health Study; AML, acute myeloid leukemia; BMI, body mass index; CLL, chronic lymphocytic leukemia; CML, chronic myeloid leukemia; CNS, central nervous system; COI, chemical of interest; dl, dioxin-like; DLBCL, diffuse large B-cell lymphoma; DLC, dioxin-like compound; DNA, deoxyribonucleic acid; FL, follicular lymphoma; GI, gastrointestinal; HD, Hodgkin disease; hpCDD, heptachlorodibenzo-p-dioxin; IARC, International Agency for Research on Cancer; IHD, ischemic heart disease; MCL, mantle cell lymphoma; MCPA, 2-methyl-4-chlorophenoxyacetic acid; MM, multiple myeloma; MZL, marginal zone lymphoma; NHANES, National Health and Nutrition Examination Survey; NHL, non-Hodgkin lymphoma; NIOSH, National Institute of Occupational Safety and Health; OCDD, octachlorodibenzo-p-dioxin; PCB, polychlorinated biphenyl; PCDD, polychlorinated dibenzo-p-dioxin; PCDF, polychlorinated dibenzofuran; PCP, pentachlorophenol; SLL, small lymphocytic lymphoma; SNP, single-nucleotide polymorphism; STS, soft-tissue sarcoma; SWHS, Seveso Women’s Health Study; TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin; TEQ, total toxic equivalent; UMHS, Upper Midwest Health Study.

not available for the entire cohort, such as data on individual serum TCDD concentrations and personal information that can be used to adjust for confounders of concern. Furthermore, even when analyses based on an entire cohort would include data on a subcohort as a subset, reports on the subcohort might provide additional information on the consistency of the relationships among subcohorts, such as whether there are important subcohort-by-exposure interaction effects, when these issues were not considered in the full-cohort studies. As long as the structures of study populations are recognized, VAO committees have been less concerned about over-weighting unstable positive findings on small subgroups or giving “repeated consideration” to duplicative results than would be the case if a quantitative meta-analysis were being undertaken.

Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

Many of the cohorts that have contributed to the cumulative findings of the VAO committees are no longer being followed; however, the cohorts’ histories are briefly recapitulated in the body of this report. Additional background information can be found in earlier reports in this series. It is notable that the literature search for this update identified only a single epidemiology study of physical (not mental) health outcomes and the COIs in Vietnam veterans (Kim et al., 2012); the Vietnam veterans were Korean servicemen and the comparisons involving presumed herbicide exposure were designed in such a fashion that the study provided no usable information on any health outcome.

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Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
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Suggested Citation:"5 Epidemiologic Studies: Compendium of New Publications." Institute of Medicine. 2014. Veterans and Agent Orange: Update 2012. Washington, DC: The National Academies Press. doi: 10.17226/18395.
×

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From 1962 to 1971, the US military sprayed herbicides over Vietnam to strip the thick jungle canopy that could conceal opposition forces, to destroy crops that those forces might depend on, and to clear tall grasses and bushes from the perimeters of US base camps and outlying fire-support bases. Mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T), picloram, and cacodylic acid made up the bulk of the herbicides sprayed. The main chemical mixture sprayed was Agent Orange, a 50:50 mixture of 2,4-D and 2,4,5-T. At the time of the spraying, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), the most toxic form of dioxin, was an unintended contaminant generated during the production of 2,4,5-T and so was present in Agent Orange and some other formulations sprayed in Vietnam.

Because of complaints from returning Vietnam veterans about their own health and that of their children combined with emerging toxicologic evidence of adverse effects of phenoxy herbicides and TCDD, the National Academy of Sciences (NAS) was asked to perform a comprehensive evaluation of scientific and medical information regarding the health effects of exposure to Agent Orange, other herbicides used in Vietnam, and the various components of those herbicides, including TCDD. Updated evaluations are conducted every two years to review newly available literature and draw conclusions from the overall evidence.Veterans and Agent Orange: Update 2012 reviews peer-reviewed scientific reports concerning associations between health outcomes and exposure to TCDD and other chemicals in the herbicides used in Vietnam that were published in October 2010--September 2012 and integrates this information with the previously established evidence database. This report considers whether a statistical association with herbicide exposure exists, taking into account the strength of the scientific evidence and the appropriateness of the statistical and epidemiological methods used to detect the association; the increased risk of disease among those exposed to herbicides during service in the Republic of Vietnam during the Vietnam era; and whether there exists a plausible biological mechanism or other evidence of a causal relationship between herbicide exposure and the disease.

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