AbstractBackgroundCholesterol reduction is considered a mechanism through which cholesterol‐lowering drugs including statins are associated with a reduced aggressive prostate cancer risk. While prior cohort studies found positive associations between total cholesterol and more advanced stage and grade in White men, whether associations for total cholesterol, low (LDL)‐ and high (HDL)‐density lipoprotein cholesterol, apolipoprotein B (LDL particle) and A1 (HDL particle), and triglycerides are similar for fatal prostate cancer and in Black men, who experience a disproportionate burden of total and fatal prostate cancer, is unknown.MethodsWe conducted a prospective study of 1553 Black and 5071 White cancer‐free men attending visit 1 (1987–1989) of the Atherosclerosis Risk in Communities Study. A total of 885 incident prostate cancer cases were ascertained through 2015, and 128 prostate cancer deaths through 2018. We estimated multivariable‐adjusted hazard ratios (HRs) of total and fatal prostate cancer per 1‐standard deviation increments and for tertiles (T1–T3) of time‐updated lipid biomarkers overall and in Black and White men.ResultsGreater total cholesterol concentration (HR per‐1 SD = 1.25; 95% CI = 1.00–1.58) and LDL cholesterol (HR per‐1 SD = 1.26; 95% CI = 0.99–1.60) were associated with higher fatal prostate cancer risk in White men only. Apolipoprotein B was nonlinearly associated with fatal prostate cancer overall (T2 vs. T1: HR = 1.66; 95% CI = 1.05–2.64) and in Black men (HR = 3.59; 95% CI = 1.53–8.40) but not White men (HR = 1.13; 95% CI = 0.65–1.97). Tests for interaction by race were not statistically significant.ConclusionsThese findings may improve the understanding of lipid metabolism in prostate carcinogenesis by disease aggressiveness, and by race while emphasizing the importance of cholesterol control.