Previously an increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), was reported among Vietnam veterans exposed to Agent Orange and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dysregulated expression of certain microRNAs (miRNAs) was demonstrated in MGUS and MM. Given the important role of miRNAs in cellular homeostasis, the aim of this study was to determine if there was an association between serum levels of selected miRNAs and TCDD in 47 MGUS cases identified in our previous investigation using serum specimens and exposure data archived by the Air Force Health Study (AFHS). A total of 13 miRNA levels (let-7a, let-7i, miR-16, miR-20a, miR-21, miR-34a, miR-106b, miR-146a, miR-181a, miR-192, miR-205, miR-335, and miR-361) was measured in serum stored during the 2002 AFHS follow-up and the relationship to lipid-adjusted serum TCDD levels in 1987 was determined. miR-34a showed the strongest relationship with TCDD; after age-adjustment, this positive association was more pronounced. In contrast, the other 12 miRNAs displayed absolute values of age adjusted coefficient estimates below 1.16 and non-significant p-values. The observed strong positive association between high body burdens of TCDD and miR-34a, a tumor suppressor regulated by p53, in this MGUS population warrants clarification of the TCDD-miR-34a relationship and its role in the pathogenesis of MGUS and risk for MM.

中文翻译：

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患有单克隆丙种球蛋白病的二恶英暴露退伍军人的血清 microRNA 谱，其意义尚未确定。

此前曾有报道称，接触橙剂及其污染物 2,3,7,8-四氯二苯并-对二恶英 (TCDD) 的越南退伍军人，患意义不明的单克隆丙种球蛋白病 (MGUS) 的风险增加，这是多发性骨髓瘤 (MM) 的前兆。 ）。MGUS 和 MM 中证实了某些 microRNA (miRNA) 的表达失调。鉴于 miRNA 在细胞稳态中的重要作用，本研究的目的是确定在我们之前使用血清样本和 Air 存档的暴露数据进行的调查中发现的 47 例 MGUS 病例中，选定 miRNA 的血清水平与 TCDD 之间是否存在关联。部队健康研究（AFHS）。总共13个miRNA水平（let-7a、let-7i、miR-16、miR-20a、miR-21、miR-34a、miR-106b、miR-146a、miR-181a、miR-192、miR-205 、miR-335 和 miR-361）在 2002 年 AFHS 随访期间储存的血清中进行了测量，并确定了与 1987 年脂质调整血清 TCDD 水平的关系。miR-34a与TCDD的关系最强；年龄调整后，这种正相关性更加明显。相比之下，其他 12 个 miRNA 显示年龄调整系数估计值的绝对值低于 1.16，p 值不显着。在该 MGUS 人群中，观察到 TCDD 和 miR-34a（一种受 p53 调节的肿瘤抑制因子）的高身体负荷之间存在强正相关性，有必要澄清 TCDD-miR-34a 关系及其在 MGUS 发病机制和 MM 风险中的作用。