Author:
Liu Lawrence W.,Wang Mei,Grandhi Nikhil,Schroeder Mark A.,Thomas Theodore,Vargo Kristin,Gao Feng,Sanfilippo Kristen M.,Chang Su-Hsin
Abstract
AbstractHerbicide 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.
Funder
Barnes-Jewish Hospital Mentors in Medicine Grant
National Institutes of Health National Cancer Institute
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Molecular Biology,Hematology
Reference12 articles.
1. Landgren O, Shim YK, Michalek J, et al. Agent orange exposure and monoclonal gammopathy of undetermined significance: an operation ranch hand veteran cohort study. JAMA Oncol. 2015;1:1061–8.
2. Munshi NC. Association of agent orange with plasma cell disorder: further evidence. JAMA Oncol. 2015;1:1035–6.
3. Stellman JM, Stellman SD, Christian R, et al. The extent and patterns of usage of agent orange and other herbicides in Vietnam. Nature. 2003;422:681–7.
4. Walker MK, Betensky RA, Carvan MJ, et al. Exposure to the herbicides used in Vietnam. National Academies Press (US), https://www.ncbi.nlm.nih.gov/books/NBK195087/ (2014) Accessed 24 Feb 2023.
5. Bumma N, Nagasaka M, Hemingway G, et al. Effect of exposure to agent orange on the risk of monoclonal gammopathy and subsequent transformation to multiple myeloma: a single-center experience from the Veterans Affairs Hospital. Detroit Clin Lymphoma Myeloma Leuk. 2020;20:305–11.