Exposure to Agent Orange and occurrence of soft-tissue sarcomas or non-Hodgkin lymphomas: an ongoing study in Vietnam.

Abstract

Agent Orange was the most common herbicide used in the Second Indochina War in the course of military operations in the former South Vietnam. Agent Orange is contaminated by the carcinogen 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD) in mean concentrations of 2 mg/kg. After much dispute of a causal association between exposure to herbicides containing TCDD and occurrence of soft-tissue sarcoma and non-Hodgkin lymphoma, two simultaneous case-control studies were set up in Vietnam to examine possible relationships. Subject recruitment is ongoing, with target numbers of 150 cases of soft-tissue sarcoma and 150 cases of non-Hodgkin lymphoma and diagnoses at the Cancer Center at Ho Chi Minh City, Vietnam. Two hospital controls are matched to each case. As in other studies of cancer in persons occupationally or otherwise exposed to herbicides and their contaminants, evaluation of past exposure of the recruited subjects is among the most complicated issues. Because accurate records are usually unavailable, surrogate measures of likely exposure are often calculated. As a first approach in our studies we used the Stellman and Stellman exposure index. The index is based on matching subjects' history of residence and the information on times and locations of Agent Orange spraying recorded on HERBS tape by the U.S. Army and taking into account the distance from the spraying as well as environmental and biologic half-life of TCDD. The exposure index is calculated in two centers, New York and Hanoi, with slightly different assumptions. In addition, samples of body tissues from the subjects (20 ml blood, 2 g adipose tissue, and tumor sections in paraffin blocks) are taken and stored. Their future analysis will provide additional source of exposure assessment. Strengths and weaknesses of both exposure measures are discussed in this paper.

Aryl Hydrocarbon Receptor Activation Suppresses EBF1 and PAX5 and Impairs Human B Lymphopoiesis

“…As a result, suppression of B lymphopoiesis by TCDD could impair the competency of humoral immunity. In addition, TCDD exposure has been epidemiologically associated with increased incidence of non-Hodgkin’s lymphoma and multiple myeloma (55–59). As the disruption of EBF1 and PAX5 has been frequently implicated in human leukemia (60, 61), the TCDD-elicited decrease of EBF1 and PAX5, as reported in this study, might contribute to the carcinogenic effect of TCDD.…”

TCDD and cancer: A critical review of epidemiologic studies

“…To assess publication bias by identifying unpublished studies is difficult. In the case of TCDD and cancer, there is at least one such example: a case-control study of STS and NHL conducted in the 1990s in Ho Chi Min City, Vietnam, on the possible association with Agent Orange exposure during the Vietnam War ( Kramarova et al, 1998 ). To the best of our knowledge no results have been reported.…”

Aryl hydrocarbon receptor activation by 2,3,7,8-tetrachlorodibenzo-p-dioxin impairs human B lymphopoiesis

“…Epidemiological studies suggest an association between exposure to TCDD and B cell disorders, most notably decreased humoral immune competence and increased incidence of B cell-derived cancers (Baccarelli et al 2002; Becher et al 1996; Floret et al 2003; Kogevinas et al 1997; Kramarova et al 1998; Viel et al 2008). In addition, several studies utilizing in vitro models reveal that TCDD suppresses human B cell activation and immunoglobulin M (IgM) antibody production (Lu et al 2011; Lu et al 2010; Wood and Holsapple 1993).…”