Abstract
Allostatic load (AL), a biomarker of chronic stress, has been implicated in the carcinogenesis of various types of cancers. However, its role in the etiology of prostate cancer is unclear. Utilizing valuable resources from the UK Biobank, we analyzed the association between AL and subsequent risk of prostate cancer in a total of 161,964 men. Levels of AL were higher in cases than in non-cancer controls (3.47 vs. 3.35, P < 0.001). In the univariate analysis, one unit increase in AL was associated with a 5% increased risk of prostate cancer (hazard ratio (HR) = 1.05, 95% Confidence Interval (CI) 1.03, 1.06). In the multivariate Cox regression analysis, the significant association was only observed among men younger than 58 years old. The significant association was further confirmed in the categorical analysis, and compared to men with AL of 0, those with AL of 1, 2, 3, 4, 5, and ≥ 6 had a statistically significantly increased risk of prostate cancer, respectively. Additionally, we observed a more than additive joint effect between AL and polygenic risk score (PRS) of prostate cancer among younger men (< 58 years old). In summary, those findings have shown that higher AL was associated with an increased prostate cancer risk in younger men.</p>