High Prevalence of Agent Orange Exposure Among Thyroid Cancer Patients in the National Va Healthcare System

Le, Karen T.; Sawicki, Mark; Wang, Marilene B.; Hershman, Jerome M.; Leung, Angela M.

doi:10.4158/ep151108.or

Cited by 11 publications

(9 citation statements)

References 17 publications

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“…These proteins with p53 participate to the Nkx2-1/p53/p65/I κ Bα pathway involved in lung carcinogenesis 30 . Here, we show that the same pathway is activated in TCDD-exposed FRTL-5 and in mice, although partially, suggesting a possible mechanism of TCDD-induced thyroid carcinogenesis in human 42 and rodents 43 . Furthermore, the reported results underline that longer exposure times are required to model in vitro the in vivo response to EDCs, as we have previously shown 34 .…”

Section: Discussionmentioning

confidence: 63%

Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice

Reale

Porreca

Russo

et al. 2018

Sci Rep

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Genetic and environmental factors contribute to thyroid diseases. Although still debated, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is thought to induce thyroid dysfunction in humans and rodents. The data here reported point out the contribution of the exposure window and genetic background in mediating the low-dose TCDD effects on thyroid. Indeed, early (from E0.5 to PND30) and low-dose (0,001 μg/kg/day) TCDD exposure reduced the circulating fT4 and altered the expression of thyroid specific transcripts. The role of genetic components was estimated monitoring the same markers in Pax8+/− and Nkx2-1+/− mice, susceptible to thyroid dysfunction, exposed to 0, 1 μg/kg/day TCDD from E15.5 to PND60. Haploinsufficiency of either Pax8 or Nkx2-1 genes exacerbated the effects of the exposure impairing the thyroid enriched mRNAs in sex dependent manner. Such effect was mediated by mechanisms involving the Nkx2-1/p53/p65/IĸBα pathway in vitro and in vivo. Foetal exposure to TCDD impaired both thyroid function and genes expression while thyroid development and differentiation did not appear significantly affected. In mouse, stronger effects were related to earlier exposure or specific genetic background such as either Pax8 or Nkx2-1 haploinsufficiency, both associated to hypothyroidism in humans. Furthermore, our data underline that long exposure time are needed to model in vitro and in vivo results.

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Section: Discussionmentioning

confidence: 63%

Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice

Reale

Porreca

Russo

et al. 2018

Sci Rep

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“…Thyroid disruption has been observed after PCBs or dioxin exposure in the general population, pregnancy and infants . An analysis of the US‐veteran affairs healthcare system showed a higher prevalence thyroid cancer in Vietnam veterans exposed to Agent Orange that was used as defoliant. In another longitudinal study, it was shown that serum TCDD levels were correlated with serum TSH levels .…”

Section: Discussionmentioning

confidence: 99%

Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

Samer

Gloor

Rollason

et al. 2019

Basic Clin Pharma Tox

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Background Dioxin (2,3,7,8‐tetrachlorodibenzo‐p‐dioxin; TCDD) is the most toxic congener of a family of structurally and mechanistically related persistent organic pollutants whose effects are mediated through the aryl hydrocarbon receptor (AhR). Induction of CYP1A1/2 by TCDD through the AhR depends on the magnitude and the duration of exposure. We aimed to assess CYP1A2 activity after acute and chronic exposure to TCDD. The Maincy cohort is a sample population from Melun in the Val‐de‐Seine region in France that lived for at least 5 years close to a waste incinerator emitting polluted vapours (1974‐2002) with high concentrations of dioxins (up to 2000 times the maximal recommended values). Acute exposure to TCDD (Viktor Yushchenko) has been described elsewhere by Sorg et al (Toxicol. Sci. 2012; 125:310‐317). Both are rare cases of well‐identified source of chronic and acute exposure to TCDD. Methods All subjects underwent a full medical history and physical examination and had a cutaneous examination, and a retro‐auricular skin biopsy was taken. A questionnaire was designed and used regarding demographic, personal, environmental and occupational characteristics. CYP1A2 activity was assessed 2 hours after the ingestion of a drink containing caffeine through measurement of the metabolic ratio of paraxanthine (17X) over caffeine (137X) by LC‐MS/MS or LC‐UV. CYP1A1 expression in skin biopsies was determined by immunohistochemical analysis. Results Forty‐seven exposed subjects (age 11‐78) and 31 controls were included in the study. Eleven exposed subjects had a history of thyroid disease (23.4%), and 7 (14.8%) had a cancer vs none and 1, respectively, in controls. Nodular skin lesions were found in 13 exposed subjects (27.7%) vs none in controls. Mean CYP1A2 activity of the exposed population was modestly elevated as compared to controls (17X/137X metabolic ratio of 0.475 vs 0.374, P = .051). CYP1A2 was, however, induced (17X/137X, metabolic ratio >0.5) in 27.6% of the exposed cases vs 6.4% of the controls. In contrast, acute dioxin exposure was associated with a strong induction (mean 17X/137X, metabolic ratio of 1.9) still present 29 months after the acute exposure. CYP1A1 was expressed in 59.6% of the skin biopsies (highly expressed in 31.9%) of the Maincy cohort. No correlation between CYP1A2 activity, CYP1A1 expression and clinical manifestations (thyroid disease, cancer, skin lesions) could be demonstrated. Conclusion Higher frequencies of dysthyroidism and cancer were detected in the population exposed chronically to dioxins from a waste incinerator. CYP1A2 was induced in 27.6% of the exposed population, while the magnitude of induction was fourfold higher after acute exposure in the case of Yushchenko.

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“…Populations with low iodine diarrhea are associated with the incidence of follicular and anaplastic carcinomas. 1 Papillary carcinoma is a type of tumor with relatively slow growth. This tumor originates from the follicular cells that produce T4 and Tg in the thyroid gland.…”

Section: Discussionmentioning

confidence: 99%

“…If any sudden onset of pain may be associated with benign lesions of the thyroid such as: thyroid bleeding or acute thyroiditis. 1,14 There are no symptoms that are typical for thyroid cancer, patients generally come with a painless lump in the neck. Anamnesis in patients with thyroid carcinoma most patients come with complaints of a lump on the anterior neck.…”

Section: Discussionmentioning

confidence: 99%

“…Thyroid lymphoma develops from the lymphoid tissue found in the thyroid tissue, while thyroid sarcoma originates from the connective tissue present in the thyroid. 1 Histopathological thyroid carcinoma classified as 78% papillary type, 13% follicular type, 2% anaplastic type and 4% medullary type. 2,3 Thyroid cancer represents about 1% of new cancer diagnoses or 23,500 cases in the United States each year.…”

Section: Introductionmentioning

confidence: 99%

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The role of thyroid stimulating hormone level as a predictive factor for advance stage thyroid carcinoma

2019

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Thyroid stimulating hormone (TSH) is a cancer growth stimulus factor that have effect on the progression of thyroid carcinoma, common neck head malignancy. This hormonelevel has diagnostic value and can assist in the diagnosis, staging and management of the thyroid carcinoma. This study aimed to investigatethe role of TSH level as a predictor of advance stage thyroid carcinoma. This was case-control study involvingthyroid enlargement subjects who underwent thyroidectomy at Dr. Sardjito General Hospital, Yogyakarta from 2015 to 2017. Cancer staging examination using AJCC 2102 and TSH levels examination were conducted before underwent thyroidectomy. The inclusion criteria for case group were advanced stage (stage III and IV), while for control group wereearlystage of thyroid carcinoma (stage I and II). The exclusion criteria for both case and control groups were 1) suffering from thyroid hormone disorders requiring therapy before thyroidectomy, 2) receiving thyroid suppression therapy prior to thyroidectomy. Sixty-six post thyroidectomy patients were involved in this study. The patients were divided into case and control groups consisted of 33 patients in each group. Based on receiver operating characteristic curve, the cut of point 1.27 mIU/L for TSH was obtained with sensitivity of 72.7% and specificity of 78.8%. There was statistically significant difference TSH levels between early stage thyroid carcinoma and late stage thyroid carcinoma (p = 0.001;OR: 9.9;95% CI: 3.19-30.15). It can be concluded that TSHlevels ≥ 1.27mIU/L as predictor of advance stage thyroid carcinoma.

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High Prevalence of Agent Orange Exposure Among Thyroid Cancer Patients in the National Va Healthcare System

Abstract: T4 = thyroxine TCDD = 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin TSH = thyroid-stimulating hormone VA = Veterans Affairs VHA = Veterans Health Administration.

Cited by 11 publications

References 17 publications

Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice

Genetic background and window of exposure contribute to thyroid dysfunction promoted by low-dose exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in mice

Cytochrome P450 1A2 activity and incidence of thyroid disease and cancer after chronic or acute exposure to dioxins

The role of thyroid stimulating hormone level as a predictive factor for advance stage thyroid carcinoma

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