Allostatic load, genetic susceptibility, incidence risk, and all-cause mortality of colorectal cancer

Abstract Background Allostatic load (AL) reflects the cumulative burden of chronic stress throughout life, potentially influencing the onset and prognosis of cancer. However, the associations between AL, colorectal cancer (CRC) risk, and all-cause mortality in patients with CRC remain unclear. Methods We analyzed the associations between AL and CRC risk in 304 959 adults and all-cause mortality in 1794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models. Results Compared with the AL level in the first quartile, individuals in the second to fourth quartiles had a respective 20%, 29%, and 43% increased risk of CRC; 15%, 24%, and 42% increased risk for colon cancer; and 30%, 38%, and 45% increased risk for rectal cancer. We identified a positive dose-gradient association of AL score with CRC risk, including colon and rectal cancer. Additionally, the association between AL and increased risk of CRC was observed across different strata of genetic susceptibility for CRC. Eliminating AL exposures could prevent nearly 39.24% (95% confidence interval [CI] = 36.16 to 42.32) of CRC events. Meanwhile, a statistically association between the AL and all-cause mortality in patients with CRC was found, with a hazard ratio of 1.71 (95% CI = 1.16 to 2.50) for the fourth quartile compared with the AL score in the first quartile, demonstrating a positive dose-response relationship. Conclusion High AL was associated with increased CRC risk and all-cause mortality in CRC patients. Future research should prioritize the development of cognitive or behavioral intervention strategies to mitigate the adverse effects of AL on CRC incidence and prognosis.