Ola Landgren1, Youn K Shim2, Joel Michalek3, Rene Costello4, Debra Burton4, Norma Ketchum3, Katherine R Calvo5, Neil Caporaso4, Elizabeth Raveche6, Dan Middleton2, Gerald Marti7, Robert F Vogt8. 1. National Cancer Institute, National Institutes of Health, Bethesda, Maryland2Memorial Sloan Kettering Cancer Center, New York, New York. 2. Agency for Toxic Substances and Disease Registry, Atlanta, Georgia. 3. Department of Epidemiology and Biostatistics, University of Texas Health Science Center, San Antonio. 4. National Cancer Institute, National Institutes of Health, Bethesda, Maryland. 5. Clinical Center, National Institutes of Health, Bethesda, Maryland. 6. Department of Pathology and Laboratory Medicine, Rutgers New Jersey Medical School, Newark. 7. Center for Devices and Radiological Health, Food and Drug Administration, Silver Spring, Maryland. 8. National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, Georgia.
Abstract
IMPORTANCE: Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans. OBJECTIVE: To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS. EXPOSURES: Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. MAIN OUTCOMES AND MEASURES: Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs. RESULTS: The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P=.007). CONCLUSIONS AND RELEVANCE: Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.
IMPORTANCE: Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans. OBJECTIVE: To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS. EXPOSURES: Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002. MAIN OUTCOMES AND MEASURES: Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs. RESULTS: The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1% (34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P=.007). CONCLUSIONS AND RELEVANCE: Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.
Authors: A S Costantini; L Miligi; D Kriebel; V Ramazzotti; S Rodella; E Scarpi; E Stagnaro; R Tumino; A Fontana; G Masala; C Viganò; C Vindigni; P Crosignani; A Benvenuti; P Vineis Journal: Epidemiology Date: 2001-01 Impact factor: 4.822
Authors: Angela Dispenzieri; Jerry A Katzmann; Robert A Kyle; Dirk R Larson; L Joseph Melton; Colin L Colby; Terry M Therneau; Raynell Clark; Shaji K Kumar; Arthur Bradwell; Rafael Fonseca; D F Jelinek; S Vincent Rajkumar Journal: Lancet Date: 2010-05-15 Impact factor: 79.321
Authors: Ola Landgren; Robert A Kyle; Ruth M Pfeiffer; Jerry A Katzmann; Neil E Caporaso; Richard B Hayes; Angela Dispenzieri; Shaji Kumar; Raynell J Clark; Dalsu Baris; Robert Hoover; S Vincent Rajkumar Journal: Blood Date: 2009-01-29 Impact factor: 22.113
Authors: Jerry A Katzmann; Raynell J Clark; Roshini S Abraham; Sandra Bryant; James F Lymp; Arthur R Bradwell; Robert A Kyle Journal: Clin Chem Date: 2002-09 Impact factor: 8.327
Authors: Kylee Maclachlan; Benjamin Diamond; Francesco Maura; Jens Hillengass; Ingemar Turesson; C Ola Landgren; Dickran Kazandjian Journal: Best Pract Res Clin Haematol Date: 2020-01-11 Impact factor: 3.020
Authors: Weixin Wang; Youn K Shim; Joel E Michalek; Emily Barber; Layla M Saleh; Byeong Yeob Choi; Chen-Pin Wang; Norma Ketchum; Rene Costello; Gerald E Marti; Robert F Vogt; Ola Landgren; Katherine R Calvo Journal: J Toxicol Environ Health A Date: 2020-04-14
Authors: Xiaomu Wei; M Nieves Calvo-Vidal; Siwei Chen; Gang Wu; Maria V Revuelta; Jian Sun; Jinghui Zhang; Michael F Walsh; Kim E Nichols; Vijai Joseph; Carrie Snyder; Celine M Vachon; James D McKay; Shu-Ping Wang; David S Jayabalan; Lauren M Jacobs; Dina Becirovic; Rosalie G Waller; Mykyta Artomov; Agnes Viale; Jayeshkumar Patel; Jude Phillip; Selina Chen-Kiang; Karen Curtin; Mohamed Salama; Djordje Atanackovic; Ruben Niesvizky; Ola Landgren; Susan L Slager; Lucy A Godley; Jane Churpek; Judy E Garber; Kenneth C Anderson; Mark J Daly; Robert G Roeder; Charles Dumontet; Henry T Lynch; Charles G Mullighan; Nicola J Camp; Kenneth Offit; Robert J Klein; Haiyuan Yu; Leandro Cerchietti; Steven M Lipkin Journal: Cancer Res Date: 2018-03-20 Impact factor: 12.701
Authors: Lei Wang; Munish Kumar; Qipan Deng; Xu Wang; Ming Liu; Zhaojian Gong; Shanshan Zhang; Xiaodong Ma; Zijun Y Xu-Monette; Min Xiao; Qing Yi; Ken H Young; Kenneth S Ramos; Yong Li Journal: Cancer Lett Date: 2018-10-19 Impact factor: 8.679
Authors: Francesco Maura; Benjamin Diamond; Kylee H Maclachlan; Andriy Derkach; Venkata D Yellapantula; Even H Rustad; Malin Hultcrantz; Urvi A Shah; Jessica Hong; Heather J Landau; Christine A Iacobuzio-Donahue; Elli Papaemmanuil; Shani Irby; Laura Crowley; Michael Crane; Mayris P Webber; David G Goldfarb; Rachel Zeig-Owens; Orsi Giricz; Amit Verma; David J Prezant; Ahmet Dogan; Sohrab P Shah; Yanming Zhang; Ola Landgren Journal: Clin Cancer Res Date: 2021-01-27 Impact factor: 13.801