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TOPLINE: A large-scale case-control study using the Million Veteran Program (MVP) found The study found independent associations of both genetic predisposition and Agent Orange (AO) exposure for several lymphoid malignant neoplasm subtypes.
METHODOLOGY:
A case-control study included 255,155 US veterans enrolled in the MVP with available genotype, Agent Orange exposure information, and lymphoid malignant neoplasm diagnosis from January 1, 1965, through June T1, 2024.
Analysis focused on non-Hispanic White veterans (median age 67 years; 92.5% male) due to ancestry distribution requirements for genome-wide association studies data availability.
Researchers excluded 628 samples across all lymphoid malignant neoplasm groups and 61,343 control samples due to unavailability of AO exposure information.
Investigators analyzed risk for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma as primary outcomes.
TAKEAWAY:
Agent Orange exposure was associated with increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% confidence interval [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 showed significant associations with all subtypes: chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93), diffuse large B-cell lymphoma (OR, 1.12; 95% CI, 1.02-1.21), follicular lymphoma (OR, 1.33; 95% CI, 1.21-1.47), marginal zone lymphoma (OR, 1.17; 95% CI, 1.04-1.32), and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).
No significant polygenic risk score and AO exposure interactions were observed in the development of any lymphoid malignant neoplasm subtypes.
The researchers found independent associations of both genetic predisposition and Agent Orange exposure on several lymphoid malignant neoplasm subtypes.
IN PRACTICE:
"Our study addressed the public health concerns surrounding AO exposure and lymphoid malignant neoplasms, finding that both AO exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation,” the authors wrote.
SOURCE: The study was led by Xueyi Teng, PhD, Department of Biological Chemistry, School of Medicine, University of California in Irvine, and Helen Ma, MD, Tibor Rubin Veterans Affairs Medical Center in Long Beach. It was published online in JAMA Network Open.
LIMITATIONS: According to the authors, while this represents the largest study of Agent Orange exposure and genetic risk in lymphoid malignant neoplasm development, the power to find interaction associations in specific subtypes might be limited. Self-reported AO exposure may have introduced survival bias, especially in aggressive subtypes, as patients with aggressive tumors might have died before joining the MVP. Additionally, approximately half of the patients were diagnosed with lymphoid malignant neoplasm before self-reporting AO exposure in the survey, potentially introducing recall bias.
DISCLOSURES: Xueyi Teng, PhD, reported receiving grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the conduct of the study. The research was supported by grant MVPOOO and Veterans Affairs Career Development Award 1IK2CX002437-O1A1. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE: A large-scale case-control study using the Million Veteran Program (MVP) found The study found independent associations of both genetic predisposition and Agent Orange (AO) exposure for several lymphoid malignant neoplasm subtypes.
METHODOLOGY:
A case-control study included 255,155 US veterans enrolled in the MVP with available genotype, Agent Orange exposure information, and lymphoid malignant neoplasm diagnosis from January 1, 1965, through June T1, 2024.
Analysis focused on non-Hispanic White veterans (median age 67 years; 92.5% male) due to ancestry distribution requirements for genome-wide association studies data availability.
Researchers excluded 628 samples across all lymphoid malignant neoplasm groups and 61,343 control samples due to unavailability of AO exposure information.
Investigators analyzed risk for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma as primary outcomes.
TAKEAWAY:
Agent Orange exposure was associated with increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% confidence interval [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 showed significant associations with all subtypes: chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93), diffuse large B-cell lymphoma (OR, 1.12; 95% CI, 1.02-1.21), follicular lymphoma (OR, 1.33; 95% CI, 1.21-1.47), marginal zone lymphoma (OR, 1.17; 95% CI, 1.04-1.32), and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).
No significant polygenic risk score and AO exposure interactions were observed in the development of any lymphoid malignant neoplasm subtypes.
The researchers found independent associations of both genetic predisposition and Agent Orange exposure on several lymphoid malignant neoplasm subtypes.
IN PRACTICE:
"Our study addressed the public health concerns surrounding AO exposure and lymphoid malignant neoplasms, finding that both AO exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation,” the authors wrote.
SOURCE: The study was led by Xueyi Teng, PhD, Department of Biological Chemistry, School of Medicine, University of California in Irvine, and Helen Ma, MD, Tibor Rubin Veterans Affairs Medical Center in Long Beach. It was published online in JAMA Network Open.
LIMITATIONS: According to the authors, while this represents the largest study of Agent Orange exposure and genetic risk in lymphoid malignant neoplasm development, the power to find interaction associations in specific subtypes might be limited. Self-reported AO exposure may have introduced survival bias, especially in aggressive subtypes, as patients with aggressive tumors might have died before joining the MVP. Additionally, approximately half of the patients were diagnosed with lymphoid malignant neoplasm before self-reporting AO exposure in the survey, potentially introducing recall bias.
DISCLOSURES: Xueyi Teng, PhD, reported receiving grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the conduct of the study. The research was supported by grant MVPOOO and Veterans Affairs Career Development Award 1IK2CX002437-O1A1. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
TOPLINE: A large-scale case-control study using the Million Veteran Program (MVP) found The study found independent associations of both genetic predisposition and Agent Orange (AO) exposure for several lymphoid malignant neoplasm subtypes.
METHODOLOGY:
A case-control study included 255,155 US veterans enrolled in the MVP with available genotype, Agent Orange exposure information, and lymphoid malignant neoplasm diagnosis from January 1, 1965, through June T1, 2024.
Analysis focused on non-Hispanic White veterans (median age 67 years; 92.5% male) due to ancestry distribution requirements for genome-wide association studies data availability.
Researchers excluded 628 samples across all lymphoid malignant neoplasm groups and 61,343 control samples due to unavailability of AO exposure information.
Investigators analyzed risk for chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, marginal zone lymphoma, and multiple myeloma as primary outcomes.
TAKEAWAY:
Agent Orange exposure was associated with increased risk for chronic lymphocytic leukemia (odds ratio [OR], 1.61; 95% confidence interval [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 showed significant associations with all subtypes: chronic lymphocytic leukemia (OR, 1.81; 95% CI, 1.70-1.93), diffuse large B-cell lymphoma (OR, 1.12; 95% CI, 1.02-1.21), follicular lymphoma (OR, 1.33; 95% CI, 1.21-1.47), marginal zone lymphoma (OR, 1.17; 95% CI, 1.04-1.32), and multiple myeloma (OR, 1.41; 95% CI, 1.31-1.52).
No significant polygenic risk score and AO exposure interactions were observed in the development of any lymphoid malignant neoplasm subtypes.
The researchers found independent associations of both genetic predisposition and Agent Orange exposure on several lymphoid malignant neoplasm subtypes.
IN PRACTICE:
"Our study addressed the public health concerns surrounding AO exposure and lymphoid malignant neoplasms, finding that both AO exposure and polygenic risk are independently associated with disease, suggesting potentially distinct and additive pathways that merit further investigation,” the authors wrote.
SOURCE: The study was led by Xueyi Teng, PhD, Department of Biological Chemistry, School of Medicine, University of California in Irvine, and Helen Ma, MD, Tibor Rubin Veterans Affairs Medical Center in Long Beach. It was published online in JAMA Network Open.
LIMITATIONS: According to the authors, while this represents the largest study of Agent Orange exposure and genetic risk in lymphoid malignant neoplasm development, the power to find interaction associations in specific subtypes might be limited. Self-reported AO exposure may have introduced survival bias, especially in aggressive subtypes, as patients with aggressive tumors might have died before joining the MVP. Additionally, approximately half of the patients were diagnosed with lymphoid malignant neoplasm before self-reporting AO exposure in the survey, potentially introducing recall bias.
DISCLOSURES: Xueyi Teng, PhD, reported receiving grants from the George E. Hewitt Foundation for Medical Research Postdoc Fellowship during the conduct of the study. The research was supported by grant MVPOOO and Veterans Affairs Career Development Award 1IK2CX002437-O1A1. No other disclosures were reported.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
