High level of dioxin-TEQ in tissue is associated with Agent Orange exposure but not with biochemical recurrence after radical prostatectomy

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'.