Mortality trends for co-occurring colon carcinoma and metabolic syndrome in the United States: A CDC WONDER analysis, 1999-2020.

e15614 Background: Colon carcinoma remains a leading cause of cancer morbidity and mortality in the United States, with persistent disparities despite advances in screening and treatment. Metabolic syndrome, affecting nearly one-third of U.S. adults, is increasingly linked to colorectal cancer risk and poorer outcomes. However, population-level data on their combined burden remain limited. Methods: Mortality data from the CDC WONDER database were analyzed for adults aged ≥45 years from 1999-2020. Deaths listing malignant neoplasms of the colon, rectosigmoid junction, and rectum (C18.0-C18.9, C19, and C20), type 2 diabetes mellitus (E11.0–E11.9), obesity (E66.0–E66.9), lipoprotein metabolism disorders and other lipidemias (E78.0–E78.9), and hypertensive diseases (ICD-10: I10–I15) as underlying or contributing causes were included. Crude and age-adjusted mortality rates (AAMRs) per 100,000 persons were standardized to the 2000 U.S. population, and temporal trends were assessed using Joinpoint regression to estimate annual (APC) and average annual percent changes (AAPC), stratified by age, race/ethnicity, state, and urban-rural status. Results: From 1999-2020, 138,431 deaths occurred among adults with colon cancer and metabolic syndrome, with overall AAMRs rising from 3.7 to 6.1 per 100,000. Age-stratified analysis showed the highest mortality in adults ≥85 years (APC 21.53, p = 0.155169) and the lowest in 45-54 years (from 0.2 to 0.8). Sex-wise, males had higher AAMRs than females (from 4.2 to 7.7 vs. 3.3 to 4.8); females exhibited sharp increases 1999-2001 (APC 16.82%, p = < 0.000), while males rose 1999-2005 (APC 5.24%, p = 0.008) and 2018-2020 (APC 12.82%, p = 0.003). Race-wise, Non-Hispanic (NH) Black or African Americans had the highest AAMRs (from 6.7-10.8), followed by NH Whites (from 3.4 to 5.9) and Hispanics (rapid increase, APC 20.48%, p = 0.045); NH American Indians showed no significant trend. Non-Hispanics exceeded Hispanics (from 3.7 to 6.1 vs. 2.1 to 5.6). Rural noncore areas had the highest mortality (from 4.0 to 8.4), and large fringe metros the lowest (from 3.3 to 5.0), with varying trends across micropolitan and other metropolitan areas. Overall mortality rose rapidly, with the steepest increase in 1999-2001 (APC 16.24%, p < 0.001) and another steady increase 2016-2020 (APC 5.07%, p < 0.001) and stable rates during 2001-2016. States with age-adjusted mortality rates above the 90th percentile included Mississippi (9.3), Nebraska (9.3), Ohio (8.4), Oklahoma (8.3), and West Virginia (8.1). Conclusions: Colorectal cancer mortality among U.S. adults with cardiometabolic comorbidities rose sharply from 1999–2020, with higher risk in males, older adults, NH Black individuals, and rural populations. Findings highlight a growing synergy between metabolic dysfunction and cancer, underscoring the need for integrated prevention and care strategies.