Abstract 1193: Allostatic load and risk of colorectal cancer in a multi-ethnic Asian cohort

Abstract Background: Allostatic load (AL) is a composite biomarker that reflects the cumulative burden of chronic stress on cardiovascular, metabolic, immune, and renal function, and is increasingly recognized as a potential contributor to cancer development. Yet, studies exploring the role of AL in cancer risk among Asian populations remain limited. This study examined the sociodemographic predictors of AL and prospectively evaluated its association with colorectal cancer (CRC) risk in a multi-ethnic Asian population. Methods: We analyzed data from the Singapore Population Health Studies (SPHS) multi-ethnic cohort of Chinese, Malays and Indians living in Singapore. AL was assessed using a composite score of nine biomarkers (BMI, SBP, DBP, HbA1C, TC, HDL, TC/HDL ratio, CRP and creatinine), with high-risk cutoffs set at the 75th percentile (≥p75) for all biomarkers except HDL, which used the 25th percentile (≤p25). High AL was categorized as a total score ≥3 (with one point for each high-risk indicator). Multivariable modified Poisson regression was conducted to assess the associations of sociodemographic factors (age, gender, ethnicity, income, education, work status) and smoking status with high AL. Cox proportional hazard regression models were used to evaluate the association between AL and CRC risk, controlling for these covariates. Results: Overall, 30, 447 participants were included in this study, with a median follow-up of 7.2 years. Two-fifths (39.7%) of the participants were categorized as having high AL, and there were 154 incident cases of CRC recorded. In multivariable analyses, older age, male gender, ethnicity (Indian or Malay compared with Chinese), ever smoking, lower education (but not household income) and being unemployed were associated with higher allostatic load scores. Participants with a university education were significantly less likely to have high AL compared to those with no formal education (aPR=0.66; 95% CI=0.63, 0.70). High AL was associated with a more than twofold increased risk of CRC in unadjusted analyses (crude HR=2.09; 95% CI=1.53, 2.85). After adjusting for sociodemographic characteristics and smoking status, high AL remained significantly associated with 47% increased risk of CRC (aHR=1.47; 95% CI=1.06, 2.05). Conclusion: These findings are consistent with prior research pointing to a positive association between allostatic load and risk of CRC. AL may serve as a valuable biomarker for the early identification of at-risk individuals and the implementation of targeted CRC prevention strategies in Asian populations. A better understanding of how demographic, lifestyle and other factors influence levels of chronic physiologic stress may also reveal important potential targets for cancer preventive interventions. Citation Format: Su Hyun Park, Isaiah Soh, Xueling Sim, Adeline Seow. Allostatic load and risk of colorectal cancer in a multi-ethnic Asian cohort [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 1193.