Abstract 4983: Allostatic load and prevalence of monoclonal gammopathy of undetermined significance

Abstract Background: Repeated exposure to stress can result in dysregulation of the endocrine system and excess secretion of hormones, even when stress is not present. The degree of dysregulation has been coined allostatic load (AL), and higher AL has been associated with increased risk of cancer. We explored the relationship of AL with the development of monoclonal gammopathy of undetermined significance (MGUS), the asymptomatic precursor to multiple myeloma, and the potential mediating effect of AL on racial disparities in MGUS prevalence. Methods: Nationally representative data from National Health and Nutrition Examination Survey (NHANES) were used. In 1999-2004, MGUS testing was performed on a subtset of participants who were 50 years or older and had available serum samples. AL was scored 0-7, based on markers of metabolic, renal, and immune physiologic systems, as previously described (Obeg-Gyasi, et al, 2022). The association of AL with MGUS was assessed using multivariable odds ratio (aOR). A mediation analysis was performed to determine the relationship of AL in the observed disparities in MGUS incidence. Results: Among the 5616 participants sampled, 2.8% had MGUS, suggesting a MGUS prevalence of 2.2% of the U.S. population above the age of 50. The characteristics of the sample with and without MGUS are compared in Table 1 Table 1 Characteristic MGUS (n=155, N=1, 364, 360) No MGUS(n = 5461, N= 60, 016, 515) P Age, mean (SD) 68.65 (1.01) 62.92 (0.22) <0.01 Male (%) 53.2 46.8 0.20 Non-Hispanic White (%) 79.4 79.9 0.03 African American or Black (%) 13.4 7.9 Hispanic (%) 3.6 8.2 Other (%) 3.6 4.0 Allostatic Load, mean (SD) 2.65 (0.11) 1.97 (0.04) <0.01 Overweight or obese (%) 80.4 71.1 0.03 Elevated Alkaline phosphatase (%) 22.1 20.7 0.68 Elevated Creatinine (%) 29.9 20.3 0.01 Reduced Creatinine Clearance (%) 31.6 16.1 <0.01 Elevated C-reactive protein (%) 32.2 22.7 <0.01 Elevated White Blood Count (%) 23.4 24.1 0.87 Reduced Albumin (%) 45.2 22.3 <0.01 . African American and Blacks were twice as likely to have MGUS compared to non-Hispanic Whites (aOR 2.00; 95% Confidence Interval [CI] 1.42-3.31; P<0.01). After adjusting for age, race, and sex, each one unit increase in AL was associated with 30% increase in odds of having MGUS (aOR=1.30; 95% CI 1.14-1.47; P<0.01). AL mediated 9.6% (95% CI -1.1%-20.3%, P=0.08) of the disparities between African American and Black and non-Hispanic White participants. Conclusions: Higher AL was associated with increased odds of MGUS. AL may also explain, at least in part, the higher incidence of MGUS among the African American and Black population in the US. Citation Format: Mark Aaron Fiala, Tuo Lan, Michael Slade, Ravi Vij, Su-Hsin Chang. Allostatic load and prevalence of monoclonal gammopathy of undetermined significance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4983.