Marian Pavuk

Diabetes and Cancer in Veterans of Operation Ranch Hand After Adjustment for Calendar Period, Days of Spraying, and Time Spent in Southeast Asia

Background: The Air Force Health Study was launched in 1980 as part of a Federal effort to resolve the Agent Orange issue. Objectives: To study diabetes and cancer with additional adjustment for days of spraying, calendar period of service, and time spent in Southeast Asia (SEA). Methods: This was a longitudinal study of veterans of Operation Ranch Hand, the unit responsible for spraying Agent Orange and other 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-contaminated herbicides in Vietnam from 1962 to 1971. Results: Associations between TCDD and diabetes and between TCDD and cancer in Ranch Hand veterans are strengthened after adjustment for calendar period of service, days of spraying, and, for cancer, time spent in SEA. Conclusions: Calendar period of service, days of spraying, and time spent in SEA are important confounders in the Air Force Health Study.

Polychlorinated Biphenyl (PCB) Exposure and Diabetes: Results from the Anniston Community Health Survey

Background: Polychlorinated biphenyls (PCBs) manufactured in Anniston, Alabama, from 1929 to 1971 caused significant environmental contamination. The Anniston population remains one of the most highly exposed in the world. Objectives: Reports of increased diabetes in PCB-exposed populations led us to examine possible associations in Anniston residents. Methods: Volunteers (n = 774) from a cross-sectional study of randomly selected households and adults who completed the Anniston Community Health Survey also underwent measurements of height, weight, fasting glucose, lipid, and PCB congener levels and verification of medications. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the relationships between PCBs and diabetes, adjusting for diabetes risk factors. Participants with prediabetes were excluded from the logistic regression analyses. Results: Participants were 47% African American, 70% female, with a mean age of 54.8 years. The prevalence of diabetes was 27% in the study population, corresponding to an estimated prevalence of 16% for Anniston overall; the PCB body burden of 35 major congeners ranged from 0.11 to 170.42 ppb, wet weight. The adjusted OR comparing the prevalence of diabetes in the fifth versus first quintile of serum PCB was 2.78 (95% CI: 1.00, 7.73), with similar associations estimated for second through fourth quintiles. In participants < 55 years of age, the adjusted OR for diabetes for the highest versus lowest quintile was 4.78 (95% CI: 1.11, 20.6), whereas in those ≥ 55 years of age, we observed no significant associations with PCBs. Elevated diabetes prevalence was observed with a 1 SD increase in log PCB levels in women (OR = 1.52; 95% CI: 1.01, 2.28); a decreased prevalence was observed in men (OR = 0.68; 95% CI: 0.33, 1.41). Conclusions: We observed significant associations between elevated PCB levels and diabetes mostly due to associations in women and in individuals < 55 years of age.

Food as a Source of Dioxin Exposure in the Residents of Bien Hoa City, Vietnam

Recently, elevated dioxin levels, over 5 parts per trillion (ppt) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), from Agent Orange was reported in 95% of 43 selected residents of Bien Hoa City, a city in southern Vietnam near a former air base used for Agent Orange-spraying missions. Agent Orange herbicide, contaminated with TCDD, was sprayed in Vietnam between 1962 and 1971 primarily for use as a defoliant. Typical blood TCCD levels are 2 ppt in Vietnamese, but levels are as high as 413 ppt in Bien Hoa City. Elevated TCDD was found in children born many years after Agent Orange spraying ended and in immigrants from non-Agent Orange-sprayed parts of Vietnam, which documented new exposures. Extremely elevated soil TCDD samples, over 1 million ppt, and elevated TCDD in sediment were found in some nearby areas such as Bien Hung Lake. The primary route of intake of almost all dioxins in humans is food. However, in our prior studies in Bien Hoa, food was unavailable for dioxin analysis so the route of intake was not confirmed. In the 1970s, while Agent Orange was still being sprayed, elevated human milk TCDD levels as high as 1850 were detected in milk from Vietnamese people living in Agent Orange-sprayed areas where consumption of fish was high. Furthermore, also in the 1970s, elevated TCDD levels (up to 810 ppt) were found in fish and shrimp from the same area as the milk donors. In the 1980s, we found elevated TCDD and also other organohalogen levels in human tissue, pork, fish, a turtle, and a snake in Southern Vietnam. For these reasons, we recently collected food from Bien Hoa and analyzed it for dioxins, polychlorinated biphenyls (PCBs), DDT and its metabolites, and other organochlorines. We found marked elevation of TCDD, the dioxin characteristic of Agent Orange, in some of the food products, including ducks with 276 ppt and 331 ppt wet weight, chickens from 0.031–15 ppt wet weight, fish from 0.063–65 ppt wet weight, and a toad with 56 ppt wet weight. Usual TCDD levels in food are less than 0.1 ppt. Total TEQ for ducks was from 286–343 ppt wet weight or 536 ppt and 550 ppt lipid; for chickens from 0.35–48 ppt wet weight or 0.95–74 ppt lipid, for fish from 0.19–66 ppt wet weight or 3.2 ppt and 15,349 ppt lipid, and the toad was 80 ppt wet weight and 11,765 ppt lipid. Interestingly, this study did not find elevated levels of TCDD in the pork and beef samples. Clearly, food, including duck, chicken, some fish, and a toad, appears responsible for elevated TCDD in residents of Bien Hoa City, even though the original Agent Orange contamination occurred 30–40 years before sampling. Elevated levels of PCBs and DDT and its metabolites were found in some food samples. Furthermore, measurable levels of hexachlorocyclohexanes (HCH) and hexachlorobenzene (HCB) were found in a wide range of measurable levels. All of the 11 dioxin-like PCBs measured and presented plus 6 dioxins in addition to TCDD and 10 dibenzofurans contributed to the total dioxin toxicity (TEQ). However, when elevated, TCDD frequently contributed most of the TEQ. Thirty-six congeners from 7 classes of chemicals were measured in each of the 16 specimens providing a total of 576 congener levels.

Did TCDD exposure or service in Southeast Asia increase the risk of cancer in air force Vietnam veterans who did not spray agent orange

Objective: We sought to examine cancer incidence in 1482 Air Force veterans who served in Southeast Asia (SEA) and who were not occupationally exposed to herbicides. Methods: Cancer incidence between 1982 and 2003 was determined by record review and Cox proportional hazards models were used to estimate risk ratios across serum 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and years served in SEA categories. Results: All sites cancer risk increased with TCDD (relative risk = 1.6, 95% confidence interval = 1.2–2.2). The risk of prostate cancer increased with years of SEA service but not with TCDD. TCDD and years of SEA service interacted with all sites cancer; the risk was greatest in those with the highest TCDD levels and the longest time served in SEA. Conclusions: These results suggest nonoccupational exposures to TCDD or other factors while in SEA may contribute to cancer risk in these veterans.

Prostate cancer in US Air Force veterans of the Vietnam war

US Air Force veterans of Operation Ranch Hand sprayed herbicides contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Vietnam from 1962 to 1971. Comparisons served in Southeast Asia (SEA) during the same time period but did not spray herbicides. Here we investigate a potential association between exposure to TCDD and prostate cancer. Data were available for 2516 veterans (1019 Ranch Hand and 1497 Comparison) who participated in at least one of six physical examinations starting in 1982 and had a measurement of serum TCDD. We assigned Ranch Hands to two exposure categories: Lower and Higher, based on their median 20-year cumulative TCDD level. In total, 81 Comparison and 59 Ranch Hand prostate cancers were identified between 1 January 1982 and 31 December 2003. We found no overall increase in the risk of prostate cancer in Ranch Hand veterans versus the Comparisons. There was a positive association in Ranch Hand veterans in the Higher TCDD category who served in SEA before 1969 (RR=2.27, 95% CI 1.11–4.66) when more contaminated herbicides were used, but the number of cases was small (n=15). A within-group comparison found that in Comparison veterans, time served in SEA was associated with an increased risk of prostate cancer (RR=2.18, 95% CI 1.27–3.76, >789 days versus ≤789 days). No increase in the risk of prostate cancer was observed within the Ranch Hand group in association with TCDD or time served in SEA. These analyses suggest that a longer service in SEA and exposures other than TCDD may have increased the risk of prostate cancer in Comparison veterans.

Reduction of the body burden of PCBs and DDE by dietary intervention in a randomized trial

Serum polychlorinated biphenyls (PCBs) in Anniston, AL, residents have been associated with hypertension and diabetes. There have been no systematic interventions to reduce PCB body burdens in Anniston or other populations. Our objective was to determine the efficacy of 15 g/day of dietary olestra to reduce PCBs in Anniston residents. Blood PCBs and 1,1-bis-(4-chlorophenyl)-2,2-dichloroethene were measured at baseline and 4-month intervals in a double-blind, placebo-controlled, 1-year trial. Participants with elevated serum PCBs were randomized into two groups of 14 and received potato crisps made with olestra or vegetable oil (VO). Elimination rates during the study period were compared with 5-year prestudy rates. Eleven participants in the olestra group and 12 in the VO group completed the study. Except for one participant in the VO group, reasons for dropout were unrelated to treatments. The elimination rate of 37 non-coplanar PCB congeners during the 1-year trial was faster during olestra consumption compared to the pretrial period (-0.0829 ± 0.0357 and -0.00864 ± 0.0116 year(-1), respectively; P=.04), but not during VO consumption (-0.0413 ± 0.0408 and -0.0283 ± 0.0096 year(-1), respectively; P=.27). The concentration of PCBs in two olestra group participants decreased by 27% and 25% during the trial. There was no significant time by group interaction in change from baseline. However, group main effects for total PCBs and PCB 153 were of borderline significance. This pilot study has demonstrated that olestra can safely reduce body burdens of PCBs and supports a larger intervention trial that may also determine whether reduction in PCBs will reduce the risk of hypertension and diabetes.

Agent Orange exposure, Vietnam War veterans, and the risk of prostate cancer.

BACKGROUND. It has been demonstrated that Agent Orange exposure increases the risk of developing several soft tissue malignancies. Federally funded studies, now nearly a decade old, indicated that there was only a weak association between exposure and the subsequent development of prostate cancer. Because Vietnam War veterans are now entering their 60s, the authors reexamined this association by measuring the relative risk of prostate cancer among a cohort of men who were stratified as either exposed or unexposed to Agent Orange between the years 1962 and 1971 and who were followed during the interval between 1998 and 2006. METHODS. All Vietnam War era veterans who receive their care in the Northern California Veteran Affairs Health System were stratified as either exposed (n = 6214) or unexposed (n = 6930) to Agent Orange. Strata-specific incidence rates of prostate cancer (International Classification of Diseases, 9th Revision code 185.0) were calculated. Differences in patient and disease characteristics (age, race, smoking history, family history, body mass index, finasteride exposure, prebiopsy prostate-specific antigen (PSA) level, clinical and pathologic stage, and Gleason score) were assessed with chi-square tests, t tests, a Cox proportional hazards model, and multivariate logistic regression. RESULTS. Twice as many exposed men were identified with prostate cancer (239 vs 124 unexposed men, respectively; odds ratio [OR], 2.19; 95% confidence interval [95% CI], 1.75-2.75). This increased risk also was observed in a Cox proportional hazards model from the time of exposure to diagnosis (hazards ratio [HR], 2.87; 95% CI, 2.31-3.57). The mean time from exposure to diagnosis was 407 months. Agent Orange-exposed men were diagnosed at a younger age (59.7 years; 95% CI, 58.9-60.5 years) compared with unexposed men (62.2 years; 95% CI, 60.8-63.6 years), had a 2-fold increase in the proportion of Gleason scores 8 through 10 (21.8%; 95% CI, 16.5%-27%) compared with unexposed men (10.5%; 95% CI, 5%-15.9%), and were more likely to have metastatic disease at presentation than men who were not exposed (13.4%; 95% CI, 9%-17.7%) than unexposed men (4%; 95% CI, 0.5%-7.5%). In univariate analysis, distribution by race, smoking history, body mass index, finasteride exposure, clinical stage, and mean prebiopsy PSA were not statistically different. In a multivariate logistic regression model, Agent Orange was the most important predictor not only of developing prostate cancer but also of high-grade and metastatic disease on presentation. CONCLUSIONS. Individuals who were exposed to Agent Orange had an increased incidence of prostate cancer; developed the disease at a younger age, and had a more aggressive variant than their unexposed counterparts. Consideration should be made to classify this group of individuals as ‘high risk,’ just like men of African-American heritage and men with a family history of prostate cancer. Cancer 2008.

Dioxin, dibenzofuran, and coplanar PCB levels in laotian blood and milk from agent Orange-sprayed and nonsprayed areas, 2001

Agent Orange, a phenoxyherbicide contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), was used by American military forces during the United States-Vietnam war between 1962 and 1971 primarily as a defoliant to destroy forests where enemy troops might find cover. Agent Orange was used mainly in Vietnam, but also to a lesser extent in Laos and Cambodia. In Laos, there have been no prior studies of TCDD contamination from Agent Orange, despite known defoliation and documented records of Agent Orange spraying. This article presents findings of TCDD in human blood and milk from two geographic areas in Laos: Vientiane, a nonsprayed area, and Sepone, an Agent Orange-sprayed area. German and Canadian laboratories used high-resolution gas chromatography-mass spectrometry to measure 7 dioxin, 10 dibenzofuran, and 4 non-ortho or coplanar polychlorinated biphenyls in Laotian blood and milk samples. Most subjects tested in this Laos Ministry of Health Study showed low dioxin and dibenzofuran levels, consistent with what would be expected in a primarily rural nonindustrial country. These findings are consistent with relatively low dioxin and dibenzofuran levels recently found in food from these same areas. The chemically and toxicologically related non-ortho PCBs were measured but were found at low levels compared to specimens from other countries, presumably because of less industrialization and industrial pollution in Laos.

Polychlorinated biphenyls and selected organochlorine pesticides in serum of Slovak population from industrial and non-industrial areas.

The concentrations of indicator polychlorinated biphenyls (PCBs No. 28, 52, 101, 138, 153 and 180) and organochlorine pesticides (HCB, p,p′-DDE and p,p′-DDT) in 121 blood serum specimens collected from non-occupationally exposed adults living in contaminated and comparison areas were determined using high-resolution gas chromatography/electron capture detection (HRGC/ECD). The sum of the serum concentrations of the three most abundant PCB congeners (No. 138, 153 and 180) found in participants (N = 81) living in industrial areas near incinerators, metallurgical and chemical plants (Krompachy, Kosice, Nemecka and Sala) was significantly higher (p < 0.001) than in participants living in villages and towns without known sources causing persistent organic pollutant (POP) contamination (N = 40). Similarly, significant differences were observed for p,p′-DDE (p < 0.0001) and p,p′-DDT (p < 0.002). However, a Mann-Whitney U test between groups showed that the difference for HCB was not statistically significant (p = 0.089). Age was positively correlated with the sum of PCBs (No. 138, 153 and 180), HCB and the sum of p,p′-DDE and p,p′-DDT (p < 0.01 for all).

Mortality, Length of Life, and Physical Examination Attendance in Participants of the Air Force Health Study

Begun in 1982, the Air Force Health Study (AFHS) has assessed the mortality of veterans of Operation Ranch Hand, the unit responsible for aerially spraying herbicides in Vietnam. A comparison group of other Air Force veterans involved with aircraft missions in Southeast Asia during the same period, but not involved with spraying herbicides, was included in the study. Among 18,082 veterans, this report examined whether attendance at AFHS physical examinations from 1982 to 1999 played a role in mortality experience and potential lengthening of life relative to veterans who did not attend. The years of potential life lost for 1173 veterans who died before age 65 was calculated. No statistically significant difference in risk of death was found from all causes, cancer, or circulatory disease between attendees and nonattendees. No evidence was found to suggest that attending physical examinations decreased mortality or substantially lengthened life in AFHS participants.