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Vietnam War veterans exposed to Agent Orange have a twofold higher prevalence of monoclonal gammopathy of undetermined significance (MGUS), compared with control veterans, providing the first scientific evidence for a link between the multiple myeloma precursor and Agent Orange exposure, researchers reported online in JAMA Oncology.
Serum samples from U.S. Air Force personnel who conducted aerial herbicide spray missions of Agent Orange in the Vietnam War from 1962 to 1971 (Operation Ranch Hand) were compared with samples from veterans who served in Vietnam during the same time period but were not involved in herbicide spray missions. The human carcinogen TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) was a contaminant found in variable amounts in Agent Orange, and levels of TCDD measured in the veteran’s serum samples were associated with cohort status. For example, TCDD levels greater than 10.92 parts per trillion were observed in 47.5% of the Ranch Hand cohort, compared with just 2.5% of the control veteran cohort. The risk of MGUS increased with increasing body burden of TCDD, although the trend was not significant.
MGUS prevalence in the Ranch Hand group was 7.1% (34 of 479) compared with 3.1% (15 of 479) in the control group (adjusted odds ratio, 2.37; 95% confidence interval, 1.27-4.44; P = .007).
“Our findings of increased MGUS risk among Ranch Hand veterans supports an association between Agent Orange exposure and multiple myeloma,” wrote Dr. Ola Landgren, Chief of Myeloma Service at Memorial Sloan Kettering, New York, and his colleagues (JAMA Oncol. 2015 Sep 3; [doi:10.1001/jamaoncol.2015.2938].
Serum samples were collected in 2002 from U.S. Air Force personnel who conducted aerial herbicide spray missions from 1962 to 1971 (n = 479) and control veterans who were not involved in the aerial missions (n = 479). The study was a follow-up of the Air Force Health Study. The first TCDD measurements were made in 1987, up to 25 years after Agent Orange exposure.
Ranch Hand veterans younger than 70 years had a significantly increased MGUS risk (OR, 3.4; 95% CI, 1.46-8.13; P = .004), but those older than 70 years had no increased MGUS risk.
Previous studies have pointed to an elevated risk of multiple myeloma among agricultural workers, and pesticides are thought to be responsible for the association.
The study was supported by the Agency for Toxic Substances and Disease Registry, the National Cancer Institute, and the Air Force Health Study Assets Research Program. Dr. Landgren reported having consulting or advisory roles with Onyx Pharmaceuticals/AMGEN, Celgene, Bristol-Myers Squibb, Jansen, and Millennium Pharmaceuticals/Takeda.
Given that all multiple myeloma cases originate from MGUS, the study by Landgren et al. provides the first scientific evidence for a direct link between multiple myeloma and exposure to Agent Orange. The study was based on well-characterized samples, a long follow-up period (25 years), and measurements of toxin exposure. The results are in line with an Agricultural Health Study that showed an almost twofold higher prevalence of MGUS among male pesticide applicators.
A weakness of this study was the variable time between exposure to Agent Orange and measurement of serum TCDD, which ranged from 16 to 25 years. It is unclear whether the peak level of TCDD exposure or the longer-term persistence of the substance in the body plays a role in MGUS transformation.
The study also highlights the importance of tissue banking to allow modern methods to investigate unanswered questions. Newer technologies can be applied to stored samples to better characterize the occurrence and progression of diseases. An important question that remains is whether TCDD exposure induces MGUS, which in turn requires additional mutations to undergo malignant transformation, or whether TCDD exposure creates the genomic instability that leads myeloma.
Dr. Nikhil Munshi is professor of medicine at the Dana-Farber Cancer Institute, Boston. These remarks were part of an editorial accompanying the report (JAMA Oncol. 2015 Sep 3; [doi:10.1001/jamaoncol.2015.2938]. Dr. Munshi had no disclosures to report.
Given that all multiple myeloma cases originate from MGUS, the study by Landgren et al. provides the first scientific evidence for a direct link between multiple myeloma and exposure to Agent Orange. The study was based on well-characterized samples, a long follow-up period (25 years), and measurements of toxin exposure. The results are in line with an Agricultural Health Study that showed an almost twofold higher prevalence of MGUS among male pesticide applicators.
A weakness of this study was the variable time between exposure to Agent Orange and measurement of serum TCDD, which ranged from 16 to 25 years. It is unclear whether the peak level of TCDD exposure or the longer-term persistence of the substance in the body plays a role in MGUS transformation.
The study also highlights the importance of tissue banking to allow modern methods to investigate unanswered questions. Newer technologies can be applied to stored samples to better characterize the occurrence and progression of diseases. An important question that remains is whether TCDD exposure induces MGUS, which in turn requires additional mutations to undergo malignant transformation, or whether TCDD exposure creates the genomic instability that leads myeloma.
Dr. Nikhil Munshi is professor of medicine at the Dana-Farber Cancer Institute, Boston. These remarks were part of an editorial accompanying the report (JAMA Oncol. 2015 Sep 3; [doi:10.1001/jamaoncol.2015.2938]. Dr. Munshi had no disclosures to report.
Given that all multiple myeloma cases originate from MGUS, the study by Landgren et al. provides the first scientific evidence for a direct link between multiple myeloma and exposure to Agent Orange. The study was based on well-characterized samples, a long follow-up period (25 years), and measurements of toxin exposure. The results are in line with an Agricultural Health Study that showed an almost twofold higher prevalence of MGUS among male pesticide applicators.
A weakness of this study was the variable time between exposure to Agent Orange and measurement of serum TCDD, which ranged from 16 to 25 years. It is unclear whether the peak level of TCDD exposure or the longer-term persistence of the substance in the body plays a role in MGUS transformation.
The study also highlights the importance of tissue banking to allow modern methods to investigate unanswered questions. Newer technologies can be applied to stored samples to better characterize the occurrence and progression of diseases. An important question that remains is whether TCDD exposure induces MGUS, which in turn requires additional mutations to undergo malignant transformation, or whether TCDD exposure creates the genomic instability that leads myeloma.
Dr. Nikhil Munshi is professor of medicine at the Dana-Farber Cancer Institute, Boston. These remarks were part of an editorial accompanying the report (JAMA Oncol. 2015 Sep 3; [doi:10.1001/jamaoncol.2015.2938]. Dr. Munshi had no disclosures to report.
Vietnam War veterans exposed to Agent Orange have a twofold higher prevalence of monoclonal gammopathy of undetermined significance (MGUS), compared with control veterans, providing the first scientific evidence for a link between the multiple myeloma precursor and Agent Orange exposure, researchers reported online in JAMA Oncology.
Serum samples from U.S. Air Force personnel who conducted aerial herbicide spray missions of Agent Orange in the Vietnam War from 1962 to 1971 (Operation Ranch Hand) were compared with samples from veterans who served in Vietnam during the same time period but were not involved in herbicide spray missions. The human carcinogen TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) was a contaminant found in variable amounts in Agent Orange, and levels of TCDD measured in the veteran’s serum samples were associated with cohort status. For example, TCDD levels greater than 10.92 parts per trillion were observed in 47.5% of the Ranch Hand cohort, compared with just 2.5% of the control veteran cohort. The risk of MGUS increased with increasing body burden of TCDD, although the trend was not significant.
MGUS prevalence in the Ranch Hand group was 7.1% (34 of 479) compared with 3.1% (15 of 479) in the control group (adjusted odds ratio, 2.37; 95% confidence interval, 1.27-4.44; P = .007).
“Our findings of increased MGUS risk among Ranch Hand veterans supports an association between Agent Orange exposure and multiple myeloma,” wrote Dr. Ola Landgren, Chief of Myeloma Service at Memorial Sloan Kettering, New York, and his colleagues (JAMA Oncol. 2015 Sep 3; [doi:10.1001/jamaoncol.2015.2938].
Serum samples were collected in 2002 from U.S. Air Force personnel who conducted aerial herbicide spray missions from 1962 to 1971 (n = 479) and control veterans who were not involved in the aerial missions (n = 479). The study was a follow-up of the Air Force Health Study. The first TCDD measurements were made in 1987, up to 25 years after Agent Orange exposure.
Ranch Hand veterans younger than 70 years had a significantly increased MGUS risk (OR, 3.4; 95% CI, 1.46-8.13; P = .004), but those older than 70 years had no increased MGUS risk.
Previous studies have pointed to an elevated risk of multiple myeloma among agricultural workers, and pesticides are thought to be responsible for the association.
The study was supported by the Agency for Toxic Substances and Disease Registry, the National Cancer Institute, and the Air Force Health Study Assets Research Program. Dr. Landgren reported having consulting or advisory roles with Onyx Pharmaceuticals/AMGEN, Celgene, Bristol-Myers Squibb, Jansen, and Millennium Pharmaceuticals/Takeda.
Vietnam War veterans exposed to Agent Orange have a twofold higher prevalence of monoclonal gammopathy of undetermined significance (MGUS), compared with control veterans, providing the first scientific evidence for a link between the multiple myeloma precursor and Agent Orange exposure, researchers reported online in JAMA Oncology.
Serum samples from U.S. Air Force personnel who conducted aerial herbicide spray missions of Agent Orange in the Vietnam War from 1962 to 1971 (Operation Ranch Hand) were compared with samples from veterans who served in Vietnam during the same time period but were not involved in herbicide spray missions. The human carcinogen TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) was a contaminant found in variable amounts in Agent Orange, and levels of TCDD measured in the veteran’s serum samples were associated with cohort status. For example, TCDD levels greater than 10.92 parts per trillion were observed in 47.5% of the Ranch Hand cohort, compared with just 2.5% of the control veteran cohort. The risk of MGUS increased with increasing body burden of TCDD, although the trend was not significant.
MGUS prevalence in the Ranch Hand group was 7.1% (34 of 479) compared with 3.1% (15 of 479) in the control group (adjusted odds ratio, 2.37; 95% confidence interval, 1.27-4.44; P = .007).
“Our findings of increased MGUS risk among Ranch Hand veterans supports an association between Agent Orange exposure and multiple myeloma,” wrote Dr. Ola Landgren, Chief of Myeloma Service at Memorial Sloan Kettering, New York, and his colleagues (JAMA Oncol. 2015 Sep 3; [doi:10.1001/jamaoncol.2015.2938].
Serum samples were collected in 2002 from U.S. Air Force personnel who conducted aerial herbicide spray missions from 1962 to 1971 (n = 479) and control veterans who were not involved in the aerial missions (n = 479). The study was a follow-up of the Air Force Health Study. The first TCDD measurements were made in 1987, up to 25 years after Agent Orange exposure.
Ranch Hand veterans younger than 70 years had a significantly increased MGUS risk (OR, 3.4; 95% CI, 1.46-8.13; P = .004), but those older than 70 years had no increased MGUS risk.
Previous studies have pointed to an elevated risk of multiple myeloma among agricultural workers, and pesticides are thought to be responsible for the association.
The study was supported by the Agency for Toxic Substances and Disease Registry, the National Cancer Institute, and the Air Force Health Study Assets Research Program. Dr. Landgren reported having consulting or advisory roles with Onyx Pharmaceuticals/AMGEN, Celgene, Bristol-Myers Squibb, Jansen, and Millennium Pharmaceuticals/Takeda.
FROM JAMA ONCOLOGY
Key clinical point: Prevalence of monoclonal gammopathy of undetermined significance (MGUS) was twofold higher in Vietnam War veterans exposed to Agent Orange, compared with veterans not exposed.
Major finding: Among veterans who conducted aerial spray missions using Agent Orange, MGUS prevalence was 7.1% (34 of 479), compared with 3.1% (15 of 479) among comparison veterans (adjusted odds ratio, 2.37; 95% CI, 1.27-4.44; P = .007).
Data source: Serum samples collected in 2002 from U.S. Air Force personnel exposed to Agent Orange from 1962 to 1971 (n = 479) and control veterans who were not involved in aerial spray missions (n = 479).
Disclosures: The study was supported by the Agency for Toxic Substances and Disease Registry, the National Cancer Institute, and the Air Force Health Study Assets Research Program. Dr. Landgren reported having consulting or advisory roles with Onyx Pharmaceuticals/AMGEN, Celgene, Bristol-Myers Squibb, Jansen, and Millennium Pharmaceuticals/Takeda.