Purpose: The association between apolipoprotein E (APOE) gene polymorphisms and prostate cancer (PCa) susceptibility exhibits population-specific variability, yet evidence in Chinese men remains limited. This study assessed the relationship between APOE variants and PCa risk, as well as their correlation with clinicopathological features in a Chinese cohort.
Methods: APOE polymorphisms (rs429358 and rs7412) were genotyped using TaqMan real-time polymerase chain reaction in 230 patients with histologically confirmed PCa. The results were compared with those of 123 age-matched patients with benign prostatic hyperplasia and 114 healthy controls. Associations between APOE genotypes and clinical variables were analyzed.
Results: No significant associations were observed between APOE variants and overall PCa risk, nor with PCa subgroups stratified by Gleason score (≤ 7 vs. >7), clinical stage (localized vs. metastatic), aggressiveness, age at onset, or biochemical recurrence. However, multivariable logistic regression demonstrated that the ε2/ε3 genotype was significantly associated with reduced PCa risk in the PSA "gray zone" (4-10 ng/mL; OR = 0.071, 95% CI: 0.008-0.645). Additionally, ε2/ε3 was inversely associated with high-PSA PCa (> 20 ng/mL; OR = 0.176, 95% CI: 0.040-0.777). Serum PSA levels were positively correlated with Gleason score in ε3/ε3 carriers (r = 0.501, P < 0.001) and ε3/ε4 carriers (r = 0.423, P = 0.008), but not in ε2/ε3 carriers (r = 0.214, P = 0.304).
Conclusions: The APOE ε2/ε3 genotype shows a protective association with PCa in Chinese men, particularly in contexts characterized by PSA-defined diagnostic uncertainty.
Keywords: Apolipoprotein E; Chinese population; Gene polymorphisms; Prostate cancer; prostate-specific antigen.
© 2026. The Author(s).