Herbicide and pesticide exposure [e.g., agent orange (AO)] is associated with an increased risk of multiple myeloma (MM) due to the contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, it is unclear whether TCDD/AO exposure (AO exposure hereafter) increases the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) to MM. We sought to evaluate the association in a nationwide study of US Veterans. A natural language processing algorithm was used to confirm MGUS and progression to MM. We included Veterans who were diagnosed with MGUS from 10/1/1999 to 12/31/2021 and served during the Vietnam War Era from 1/9/1962 to 5/7/1975. AO exposure was stratified according to three TCDD exposure levels: high (1/9/1962–11/30/1965), medium (12/1/1965–12/31/1970), or low (1/1/1971–5/7/1975). The association between AO exposure and progression was analyzed using multivariable Fine-Gray subdistribution hazard model with death as a competing event. The analytic cohort included 10,847 Veterans with MGUS, of whom 26.3% had AO exposure and 7.4% progressed to MM over a median follow-up of 5.2 years. In multivariable analysis, high exposure was associated with an increased progression rate (multivariable-adjusted hazard ratio 1.48; 95% confidence interval 1.02–2.16), compared to Veterans with no exposure. This information is critical to inform progression risk in patients diagnosed with MGUS and prior AO exposure. It is also applicable to MGUS patients with occupational TCDD exposure from herbicides and pesticides.

中文翻译：

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橙剂暴露与单克隆丙种球蛋白病对多发性骨髓瘤意义未明的进展之间的关系：一项针对越战时期退伍军人的基于人群的研究

由于污染物 2,3,7,8-四氯二苯并-对二恶英 (TCDD)，除草剂和杀虫剂接触[例如橙剂 (AO)] 与多发性骨髓瘤 (MM) 的风险增加相关。然而，尚不清楚 TCDD/AO 暴露（以下简称 AO 暴露）是否会增加意义未明的单克隆丙种球蛋白病 (MGUS) 进展为 MM 的风险。我们试图通过一项针对美国退伍军人的全国性研究来评估这种关联。使用自然语言处理算法来确认 MGUS 和进展为 MM。我们纳入了在 1999 年 1 月 1 日至 2021 年 12 月 31 日期间被诊断患有 MGUS 并在 1962 年 1 月 9 日至 1975 年 5 月 7 日在越南战争期间服役的退伍军人。AO暴露根据三个TCDD暴露水平进行分层：高（1/9/1962–11/30/1965）、中（12/1/1965–12/31/1970）或低（1/1/1971– 1975 年 5 月 7 日）。使用多变量细灰色亚分布风险模型（以死亡作为竞争事件）分析 AO 暴露与进展之间的关联。分析队列包括 10,847 名患有 MGUS 的退伍军人，其中 26.3% 患有 AO 暴露，7.4% 在中位随访时间 5.2 年中进展为 MM。在多变量分析中，与没有暴露的退伍军人相比，高暴露与进展率增加相关（多变量调整风险比 1.48；95% 置信区间 1.02–2.16）。该信息对于了解诊断为 MGUS 且既往 AO 暴露的患者的进展风险至关重要。它也适用于因除草剂和杀虫剂职业性接触 TCDD 的 MGUS 患者。