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TOPLINE: Agent Orange exposure was associated with a 26% to 71% increased risk for multiple lymphoid cancers in veterans enrolled in the US Department of Veterans Affairs (VA) Million Veterans Program (MVP), while genetic predisposition independently raised risk by 12% to 81% across different lymphoma subtypes. A case-controlled analysis of 255,155 veterans found no significant interaction between genetic risk scores and Agent Orange exposure.
METHODOLOGY:
A case-control study included 255,155 non-Hispanic White veterans (median age 67 years, 92.5% male) enrolled in the VA MVP with genotype and Agent Orange exposure data.
Researchers analyzed five lymphoid malignant neoplasm subtypes: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma diagnosed from January 1965 through June 2024.
Agent Orange exposure was determined through self-reported survey responses, while polygenic risk scores were derived from genome-wide association studies of lymphoid malignant neoplasms.
Analysis included adjustments for age at enrollment, sex, and the first 10 genetic principal components in logistic regression models evaluating Agent Orange exposure, polygenic risk scores, and their potential interaction.
TAKEAWAY:
Agent Orange exposure significantly increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% CI, 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).
Polygenic risk scores were independently associated with all lymphoma subtypes, with strongest associations for chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93) and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).
Analysis in African American participants showed similar associations for multiple myeloma with both Agent Orange exposure (OR, 1.56; 95% CI, 1.18-2.07) and polygenic risk scores (OR, 1.31; 95% CI, 1.15-1.49).
According to the researchers, no significant polygenic risk score and Agent Orange exposure interactions were observed for any lymphoma subtype.
IN PRACTICE: "Our study addressed the public health concerns surrounding Agent Orange exposure and lymphoid malignant neoplasms, finding that both Agent Orange exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation," wrote the authors of the study.
SOURCE: The study was led by researchers at the University of California, Irvine and the Tibor Rubin Veterans Affairs Medical Center, Long Beach, Californiaand was published online on August 13 in JAMA Network Open.
LIMITATIONS: According to the authors, while this represents the largest case-control study of Agent Orange exposure and lymphoid malignant neoplasm risk, the power to detect interaction associations in specific subtypes might be limited. Self-reported Agent Orange exposure data may have introduced survival bias, particularly in aggressive subtypes, as patients with aggressive tumors may have died before joining the MVP. Additionally, about half of the patients were diagnosed with lymphoid malignant neoplasms before self-reporting Agent Orange exposure, potentially introducing recall bias.
DISCLOSURES: The research was supported by a Veterans Affairs Career Development Award Xueyi Teng, PhD, received grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the study.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE: Agent Orange exposure was associated with a 26% to 71% increased risk for multiple lymphoid cancers in veterans enrolled in the US Department of Veterans Affairs (VA) Million Veterans Program (MVP), while genetic predisposition independently raised risk by 12% to 81% across different lymphoma subtypes. A case-controlled analysis of 255,155 veterans found no significant interaction between genetic risk scores and Agent Orange exposure.
METHODOLOGY:
A case-control study included 255,155 non-Hispanic White veterans (median age 67 years, 92.5% male) enrolled in the VA MVP with genotype and Agent Orange exposure data.
Researchers analyzed five lymphoid malignant neoplasm subtypes: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma diagnosed from January 1965 through June 2024.
Agent Orange exposure was determined through self-reported survey responses, while polygenic risk scores were derived from genome-wide association studies of lymphoid malignant neoplasms.
Analysis included adjustments for age at enrollment, sex, and the first 10 genetic principal components in logistic regression models evaluating Agent Orange exposure, polygenic risk scores, and their potential interaction.
TAKEAWAY:
Agent Orange exposure significantly increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% CI, 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).
Polygenic risk scores were independently associated with all lymphoma subtypes, with strongest associations for chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93) and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).
Analysis in African American participants showed similar associations for multiple myeloma with both Agent Orange exposure (OR, 1.56; 95% CI, 1.18-2.07) and polygenic risk scores (OR, 1.31; 95% CI, 1.15-1.49).
According to the researchers, no significant polygenic risk score and Agent Orange exposure interactions were observed for any lymphoma subtype.
IN PRACTICE: "Our study addressed the public health concerns surrounding Agent Orange exposure and lymphoid malignant neoplasms, finding that both Agent Orange exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation," wrote the authors of the study.
SOURCE: The study was led by researchers at the University of California, Irvine and the Tibor Rubin Veterans Affairs Medical Center, Long Beach, Californiaand was published online on August 13 in JAMA Network Open.
LIMITATIONS: According to the authors, while this represents the largest case-control study of Agent Orange exposure and lymphoid malignant neoplasm risk, the power to detect interaction associations in specific subtypes might be limited. Self-reported Agent Orange exposure data may have introduced survival bias, particularly in aggressive subtypes, as patients with aggressive tumors may have died before joining the MVP. Additionally, about half of the patients were diagnosed with lymphoid malignant neoplasms before self-reporting Agent Orange exposure, potentially introducing recall bias.
DISCLOSURES: The research was supported by a Veterans Affairs Career Development Award Xueyi Teng, PhD, received grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the study.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE: Agent Orange exposure was associated with a 26% to 71% increased risk for multiple lymphoid cancers in veterans enrolled in the US Department of Veterans Affairs (VA) Million Veterans Program (MVP), while genetic predisposition independently raised risk by 12% to 81% across different lymphoma subtypes. A case-controlled analysis of 255,155 veterans found no significant interaction between genetic risk scores and Agent Orange exposure.
METHODOLOGY:
A case-control study included 255,155 non-Hispanic White veterans (median age 67 years, 92.5% male) enrolled in the VA MVP with genotype and Agent Orange exposure data.
Researchers analyzed five lymphoid malignant neoplasm subtypes: chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma diagnosed from January 1965 through June 2024.
Agent Orange exposure was determined through self-reported survey responses, while polygenic risk scores were derived from genome-wide association studies of lymphoid malignant neoplasms.
Analysis included adjustments for age at enrollment, sex, and the first 10 genetic principal components in logistic regression models evaluating Agent Orange exposure, polygenic risk scores, and their potential interaction.
TAKEAWAY:
Agent Orange exposure significantly increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% CI, 1.40-1.84), diffuse large B-cell lymphoma (OR, 1.26; 95% CI, 1.03-1.53), follicular lymphoma (OR, 1.71; 95% CI, 1.39-2.11), and multiple myeloma (OR, 1.58; 95% CI, 1.35-1.86).
Polygenic risk scores were independently associated with all lymphoma subtypes, with strongest associations for chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93) and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).
Analysis in African American participants showed similar associations for multiple myeloma with both Agent Orange exposure (OR, 1.56; 95% CI, 1.18-2.07) and polygenic risk scores (OR, 1.31; 95% CI, 1.15-1.49).
According to the researchers, no significant polygenic risk score and Agent Orange exposure interactions were observed for any lymphoma subtype.
IN PRACTICE: "Our study addressed the public health concerns surrounding Agent Orange exposure and lymphoid malignant neoplasms, finding that both Agent Orange exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation," wrote the authors of the study.
SOURCE: The study was led by researchers at the University of California, Irvine and the Tibor Rubin Veterans Affairs Medical Center, Long Beach, Californiaand was published online on August 13 in JAMA Network Open.
LIMITATIONS: According to the authors, while this represents the largest case-control study of Agent Orange exposure and lymphoid malignant neoplasm risk, the power to detect interaction associations in specific subtypes might be limited. Self-reported Agent Orange exposure data may have introduced survival bias, particularly in aggressive subtypes, as patients with aggressive tumors may have died before joining the MVP. Additionally, about half of the patients were diagnosed with lymphoid malignant neoplasms before self-reporting Agent Orange exposure, potentially introducing recall bias.
DISCLOSURES: The research was supported by a Veterans Affairs Career Development Award Xueyi Teng, PhD, received grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the study.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.