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 association between AL and CRC risk in 304,959 adults and all-cause mortality in 1,794 patients with CRC from the UK Biobank, using Cox proportional hazards regression models. Results Compared to 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% CI: 36.16-42.32) of CRC incident cases. Meanwhile, a significant association between the AL and all-cause mortality in patients with CRC was found, with a HR of 1.71 (95% CI: 1.16-2.50) for the fourth quartile compared to 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.

中文翻译：

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结直肠癌的稳态负荷、遗传易感性、发病风险和全因死亡率


背景 稳态负荷（AL）反映了一生中慢性压力的累积负担，可能影响癌症的发病和预后。然而，AL、结直肠癌 (CRC) 风险和 CRC 患者全因死亡率之间的关联仍不清楚。方法 我们使用 Cox 比例风险回归模型分析了英国生物库中 304,959 名成人的 AL 和 CRC 风险以及 1,794 名 CRC 患者的全因死亡率之间的关联。结果 与第一个四分位数的 AL 水平相比，第二至第四个四分位数的个体患 CRC 的风险分别增加了 20%、29% 和 43%；结肠癌风险增加 15%、24% 和 42%；直肠癌的风险增加 30%、38% 和 45%。我们发现 AL 评分与 CRC 风险（包括结肠癌和直肠癌）呈正剂量梯度关联。此外，在不同 CRC 遗传易感性阶层中观察到 AL 与 CRC 风险增加之间的关联。消除 AL 暴露可以预防近 39.24%（95% CI：36.16-42.32）的 CRC 病例。同时，发现 CRC 患者的 AL 与全因死亡率之间存在显着相关性，与第一个四分位数的 AL 评分相比，第四个四分位数的 HR 为 1.71（95% CI：1.16-2.50），这表明正剂量反应关系。结论 高 AL 与 CRC 患者的 CRC 风险和全因死亡率增加相关。未来的研究应优先发展认知或行为干预策略，以减轻 AL 对 CRC 发病率和预后的不利影响。