APOE ε2/ε3 is associated with multi-layered protection against prostate cancer in Chinese men

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. 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. 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). The APOE ε2/ε3 genotype shows a protective association with PCa in Chinese men, particularly in contexts characterized by PSA-defined diagnostic uncertainty.