Serum microRNA profiles among dioxin exposed veterans with monoclonal gammopathy of undetermined significance
| Autor: | Emily Barber, Joel E. Michalek, Gerald E. Marti, Layla M. Saleh, Weixin Wang, Katherine R. Calvo, Norma S. Ketchum, Rene Costello, Ola Landgren, Byeong Yeob Choi, Youn K. Shim, Chen Pin Wang, Robert F. Vogt |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Polychlorinated Dibenzodioxins Materials science Health Toxicology and Mutagenesis Population Cellular homeostasis Toxicology Monoclonal Gammopathy of Undetermined Significance Article Pathogenesis 03 medical and health sciences 0302 clinical medicine Internal medicine microRNA medicine Humans Prospective Studies Prospective cohort study education Multiple myeloma Aged Veterans Aged 80 and over education.field_of_study Herbicides Middle Aged medicine.disease United States MicroRNAs Circulating MicroRNA 030104 developmental biology Endocrinology 030220 oncology & carcinogenesis Monoclonal gammopathy of undetermined significance |
| Zdroj: | J Toxicol Environ Health A |
| ISSN: | 1087-2620 1528-7394 |
| DOI: | 10.1080/15287394.2020.1749919 |
| Popis: | We previously reported an increased risk for monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma (MM), among Vietnam veterans exposed to Agent Orange and its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Dysregulated expression of certain microRNAs (miRNAs) has been demonstrated in MGUS and MM. Given the important role of miRNAs in cellular homeostasis, we sought to determine if there was an association between serum levels of selected miRNAs and TCDD in 47 MGUS cases identified in our previous study, using serum specimens and exposure data archived by the Air Force Health Study (AFHS). We measured 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) in serum stored during the 2002 AFHS follow-up and evaluated their relationship to lipid-adjusted serum TCDD levels in 1987 determined by the AFHS. miR-34a showed the strongest association with TCDD (coefficient 2.184, p-value 0.02); after age-adjustment, this positive association was more pronounced (coefficient 2.294, p-value 0.008). In contrast, the other 12 miRNAs had absolute values of age-adjusted coefficient estimates below 1.16 and p-values greater than 0.18. The observed strong positive relationship 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. |
| Databáze: | OpenAIRE |
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