Mei Wang, Byron Sigel, Lawrence Liu, John H Huber, Mengmeng Ji, Martin W Schoen, Kristen M Sanfilippo, Theodore S Thomas, Graham A Colditz, Shi-Yi Wang, Su-Hsin Chang
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Unlike other malignancies, such evidence is lacking for MM despite its high burden.</p><p><strong>Objective: </strong>To quantify contributions of modifiable risk factors to MGUS progression to MM to inform prevention.</p><p><strong>Design: </strong>Retrospective cohort study conducted from 1/1/2024-12/31/2024.</p><p><strong>Setting: </strong>Nationwide U.S. Veterans Health Administration (VHA).</p><p><strong>Participants: </strong>Patients with MGUS (IgG, IgA, or light chain) diagnosed from 10/1/1999-12/31/2023.</p><p><strong>Interventions: </strong>Modifiable risk factors including excess body mass index (BMI), chemical exposure, and comorbidities.</p><p><strong>Measurements: </strong>Excess body mass index was defined as BMI ≥25 kg/m2, chemical exposure was measured by prior exposure to Agent Orange, comorbidities were summarized using Charlson Comorbidity Index. Multivariable-adjusted population attributable fractions (aPAF) was calculated for each modifiable risk factor. The aPAF estimates the proportion of progression in patients diagnosed with MGUS that could have been prevented, if a given risk factor were absent.</p><p><strong>Results: </strong>The cohort included 35,073 MGUS patients (33,670 [96.0%] male and 23,218 [66.2%] White), of whom 2,895 (8.3%) progressed to MM. Median age at MGUS diagnosis was 71.8 (IQR: 64.4-78.6) years. Among all evaluated risk factors, excess BMI was the leading factor (Black: aPAF=27.1%, 95% CI 19.5-34.0%; White: 27.2%, 95% CI 20.3-33.4%; All: aPAF=27.1%, 95% CI: 22.1-31.9%).</p><p><strong>Limitations: </strong>Potential residual confounding, limited generalizability beyond the VHA population.</p><p><strong>Conclusion: </strong>Our study highlights the potential for weight management as a key strategy in reducing the risk of progression to MM in Black and White patients diagnosed with MGUS.</p><p><strong>Primary funding source: </strong>National Institutes of Health.</p>","PeriodicalId":94281,"journal":{"name":"medRxiv : the preprint server for health sciences","volume":" ","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12045440/pdf/","citationCount":"0","resultStr":"{\"title\":\"Quantify the Contribution of Modifiable Risk Factors for Progression of MGUS to Multiple Myeloma.\",\"authors\":\"Mei Wang, Byron Sigel, Lawrence Liu, John H Huber, Mengmeng Ji, Martin W Schoen, Kristen M Sanfilippo, Theodore S Thomas, Graham A Colditz, Shi-Yi Wang, Su-Hsin Chang\",\"doi\":\"10.1101/2025.04.21.25326164\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Multiple myeloma (MM), the most common plasma cell dyscrasia in the U.S., is preceded by an asymptomatic precursor monoclonal gammopathy of undetermined significance (MGUS). 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引用次数: 0
摘要
目的：多发性骨髓瘤（MM）是美国最常见的浆细胞病变，存在显著的健康差异。MM之前有一种未确定意义的无症状前体单克隆γ病（MGUS）。研究已经确定了MGUS发展为MM的几个危险因素；然而，这些因素的相对贡献仍然未知。特别是，了解这些可改变因素之间的作用可以为预防MM提供信息。方法：本研究通过估计MGUS退伍军人中MM可变危险因素的调整人群归因分数（aPAF）来量化这些贡献。结果：在所有评估的危险因素中，超重体重指数（BMI≥25 kg/ m2）是主要因素(Black: aPAF=27.0%, 95% CI 19.3-33.9%；白色：27.1%,95% CI 20.3-33.4%；aPAF=27.1%, 95% CI: 22.0-31.8%)。结论：我们的研究强调了体重管理作为降低被诊断为MGUS的黑人和白人患者进展为MM风险的关键策略的潜力。
Quantify the Contribution of Modifiable Risk Factors for Progression of MGUS to Multiple Myeloma.
Background: Multiple myeloma (MM), the most common plasma cell dyscrasia in the U.S., is preceded by an asymptomatic precursor monoclonal gammopathy of undetermined significance (MGUS). Although several risk factors for MGUS progression are known, their relative contributions remain unclear. Unlike other malignancies, such evidence is lacking for MM despite its high burden.
Objective: To quantify contributions of modifiable risk factors to MGUS progression to MM to inform prevention.
Design: Retrospective cohort study conducted from 1/1/2024-12/31/2024.
Setting: Nationwide U.S. Veterans Health Administration (VHA).
Participants: Patients with MGUS (IgG, IgA, or light chain) diagnosed from 10/1/1999-12/31/2023.
Interventions: Modifiable risk factors including excess body mass index (BMI), chemical exposure, and comorbidities.
Measurements: Excess body mass index was defined as BMI ≥25 kg/m2, chemical exposure was measured by prior exposure to Agent Orange, comorbidities were summarized using Charlson Comorbidity Index. Multivariable-adjusted population attributable fractions (aPAF) was calculated for each modifiable risk factor. The aPAF estimates the proportion of progression in patients diagnosed with MGUS that could have been prevented, if a given risk factor were absent.
Results: The cohort included 35,073 MGUS patients (33,670 [96.0%] male and 23,218 [66.2%] White), of whom 2,895 (8.3%) progressed to MM. Median age at MGUS diagnosis was 71.8 (IQR: 64.4-78.6) years. Among all evaluated risk factors, excess BMI was the leading factor (Black: aPAF=27.1%, 95% CI 19.5-34.0%; White: 27.2%, 95% CI 20.3-33.4%; All: aPAF=27.1%, 95% CI: 22.1-31.9%).
Limitations: Potential residual confounding, limited generalizability beyond the VHA population.
Conclusion: Our study highlights the potential for weight management as a key strategy in reducing the risk of progression to MM in Black and White patients diagnosed with MGUS.
Primary funding source: National Institutes of Health.
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