"The accelerating burden of Colorectal cancer mortality With Co-documented metabolic comorbidity in the United States: A 26-year analysis of trends, disparities, and projections to 2031".

BACKGROUND

Colorectal cancer (CRC), the second leading cause of cancer-related death worldwide, has declined in the United States over the past two decades due to expanded screening and improved systemic therapies. Although mortality has decreased in older adults, recent data suggest an increasing trend in younger populations. The concurrent rise in metabolic comorbidities may be contributing; however, no national multi-decade study has evaluated trends, disparities, and trajectories in CRC mortality with co-existing metabolic comorbidity.

METHODS

Using the CDC WONDER Multiple Cause-of-Death database (1999-2024), we identified decedents aged ≥25 years with CRC as the underlying cause and ≥1 metabolic condition (obesity, Type-2 DM, hypertension, dyslipidemia) listed in any death-certificate field, representing co-documented metabolic comorbidity. Age-adjusted mortality rates (AAMRs) were calculated by direct standardization. Joinpoint regression assessed temporal trends, and ARIMA modeling projected mortality through 2031.

RESULTS

From 1999 to 2024, overall CRC AAMR declined by ∼40% (32.06 to 19.38 per 100,000; AAPC -2.04%), whereas CRC with metabolic comorbidity AAMR nearly doubled (1.37 to 2.47 per 100,000; AAPC +2.01%). The proportion of CRC deaths with co-documented metabolic comorbidity tripled, from 4.27% to 13.03%. Steepest increases occurred for dyslipidemia (+7.65%), adults aged 25-44 years (+6.70%), males (+2.80%), Hispanic (+4.16%) and White (+2.22%) individuals, Southern region (+3.92%), and noncore rural areas (+2.48%). ARIMA projections estimate growth to 2.81 per 100,000 by 2031 (+13.8% increase).

CONCLUSIONS

CRC mortality with co-documented metabolic comorbidity is rising despite an overall decline in CRC mortality, highlighting an increasing metabolic burden among CRC decedents. Persistent demographic and geographic disparities underscore the need for integrated metabolic-oncologic care and targeted prevention strategies.