Agent Orange exposure and prostate cancer risk in the Million Veteran Program.
Agent Orange exposure and prostate cancer risk in the Million Veteran Program.
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百万退伍军人计划中的橙剂暴露和前列腺癌风险。
DOI：
10.1101/2023.06.14.23291413
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Seibert,TylerM
中科院分区：
文献类型：
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作者：
Lui,AsonaJ;Pagadala,MeghanaS;Zhong,AllisonY;Lynch,Julie;Karunamuni,Roshan;Lee,KyungMin;Plym,Anna;Rose,BrentS;Carter,Hannah;Kibel,AdamS;DuVall,ScottL;Gaziano,JMichael;Panizzon,MatthewS;Hauger,RichardL;Seibert,TylerM
目的接触橙剂（一种已知的致癌物质）可能会增加患前列腺癌 (PCa) 的风险。我们试图在考虑不同美国越战退伍军人的种族/族裔、家族史和遗传风险时，调查橙剂暴露与 PCa 风险之间的关联。方法和材料本研究利用了百万退伍军人计划 (MVP)，这是一项针对美国退伍军人的全国性、基于人群的队列研究，于 2011 年至 2021 年进行，有 590,750 名男性参与者可供分析。橙剂暴露情况是根据退伍军人事务部 (VA) 的记录获得的，该记录使用了美国政府对橙剂暴露的定义：在使用橙剂期间在越南服役。此分析仅包括越南战争期间（世界任何地方）现役的退伍军人（211,180 名参与者）。通过先前验证的根据基因型数据计算的多基因风险评分来评估遗传风险。通过 Cox 比例风险模型评估任何 PCa 的诊断年龄、转移性 PCa 的诊断以及 PCa 的死亡。结果暴露于橙剂与 PCa 诊断增加相关（HR 1.04，95% CI 1.01–1.06，p=0.003），主要是在非西班牙裔白人男性中（HR 1.09，95% CI 1.06–1.12， p<0.001）。当考虑种族/族裔和家族史时，橙剂暴露仍然是 PCa 诊断的独立危险因素（HR 1.06，95% CI 1.04–1.09，p<0.05）。橙剂暴露与 PCa 转移（HR 1.08，95% CI 0.99–1.17）和 PCa 死亡（HR 1.02，95% CI 0.84–1.22）的单变量关联在多变量分析中未达到显着性。在考虑多基因风险评分时也发现了类似的结果。结论在美国越战退伍军人中，橙剂暴露是 PCa 诊断的独立风险因素，尽管在考虑种族/族裔、家族史和/或多基因风险时与 PCa 转移或死亡的关联尚不清楚。
PurposeExposure to Agent Orange, a known carcinogen, might increase risk of prostate cancer (PCa). We sought to investigate the association of Agent Orange exposure and PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population of US Vietnam War veterans.Methods & MaterialsThis study utilized the Million Veteran Program (MVP), a national, population-based cohort study of United States military veterans conducted 2011-2021 with 590,750 male participants available for analysis. Agent Orange exposure was obtained using records from the Department of Veterans Affairs (VA) using the US government definition of Agent Orange exposure: active service in Vietnam while Agent Orange was in use. Only veterans who were on active duty (anywhere in the world) during the Vietnam War were included in this analysis (211,180 participants). Genetic risk was assessed via a previously validated polygenic hazard score calculated from genotype data. Age at diagnosis of any PCa, diagnosis of metastatic PCa, and death from PCa were assessed via Cox proportional hazards models.ResultsExposure to Agent Orange was associated with increased PCa diagnosis (HR 1.04, 95% CI 1.01–1.06, p=0.003), primarily among Non-Hispanic White men (HR 1.09, 95% CI 1.06– 1.12, p<0.001). When accounting for race/ethnicity and family history, Agent Orange exposure remained an independent risk factor for PCa diagnosis (HR 1.06, 95% CI 1.04–1.09, p<0.05). Univariable associations of Agent Orange exposure with PCa metastasis (HR 1.08, 95% CI 0.99–1.17) and PCa death (HR 1.02, 95% CI 0.84–1.22) did not reach significance on multivariable analysis. Similar results were found when accounting for polygenic hazard score.ConclusionsAmong US Vietnam War veterans, Agent Orange exposure is an independent risk factor for PCa diagnosis, though associations with PCa metastasis or death are unclear when accounting for race/ethnicity, family history, and/or polygenic risk.