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

Q: What was the study designed to evaluate?

The study assessed the relationship between APOE variants and prostate cancer risk in Chinese men, and how these variants correlate with clinicopathological features.

Q: Which PSA-related subgroup showed a significant association with ε2/ε3?

Multivariable logistic regression found ε2/ε3 associated with reduced risk in the PSA “gray zone” (4–10 ng/mL) and inversely associated with high-PSA PCa (>20 ng/mL).

Sep 23, 2026

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Study purpose targets how apolipoprotein E (APOE) gene polymorphisms relate to prostate cancer (PCa) susceptibility, emphasizing limited evidence in Chinese men. Methods genotype APOE variants (rs429358, rs7412) via TaqMan real-time PCR in 230 histologically confirmed PCa patients, compared with 123 benign prostatic hyperplasia patients and 114 healthy controls, with clinicopathologic correlations. Results show no overall PCa risk association, but multivariable analysis links ε2/ε3 to reduced risk within the PSA “gray zone” and higher-PSA PCa; ε3/ε3 and ε3/ε4 correlate with Gleason score, not ε2/ε3. Conclusions indicate a protective ε2/ε3 association, especially where PSA-defined diagnostic uncertainty exists.

LanguageEnglish

CategoryHealthcare

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Abstract

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World Journal of Urology (2026) 44:361 [https://doi.org/10.1007/s00345-026-06459-1](https://doi.org/10.1007/s00345-026-06459-1) RESEARCH APOE ε2/ε3 is associated with multi-layered protection against prostate cancer in Chinese men Kuan Wang1 · Shizhen Zhang2,3 · Mengli Chen1 · Xiuzhi Duan1 · Yiyi Xie1 · Xufeng Yang1 · Yuhong Zhong1 · Pan Yu1 · Meiying Yang1 · Zhenli Wei1 · Zhihua Tao1 · Weiwei Liu1 Received: 16 December 2025 / Accepted: 30 April 2026 © The Author(s) 2026 Abstract 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 · Prostate cancer · Chinese population · Gene polymorphisms · prostate-specific antigen Kuan Wang and Shizhen Zhang Contributed equally to this work. 􀀍 Zhihua Tao[zrtzh@zju.edu.cn](zrtzh@zju.edu.cn) 􀀍 Weiwei Liu [liuweiwei@zju.edu.cn](liuweiwei@zju.edu.cn) 1 Department of Laboratory Medicine, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China 2 Department of Breast Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310029, China 3 Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, National Ministry of Education), the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310029, China Introduction Globally, prostate cancer (PCa) accounts for an estimated 1.5 million new diagnoses and nearly 400,000 deaths annually, making it the most frequently diagnosed malignancy in approximately two-thirds of countries worldwide [1] . Roughly 75% of patients present with localized disease, which is associated with a nearly 100% five-year survival rate. Management strategies for localized PCa, including active surveillance, radical prostatectomy, and radiation therapy, are tailored to the risk of disease progression. In contrast, approximately 10% of patients are diagnosed with metastatic prostate cancer (mPCa), which has a far poorer prognosis, with a five-year survival rate of only 37%[2] . Established risk factors for PCa include advanced age, African or Caribbean ancestry, positive family history, and specific genetic mutations. However, definitive environmental or lifestyle risk factors remain largely unidentified [1] . Notably, significant racial disparities exist in PCa incidence, morbidity, and mortality. Men of African American descent face a

FAQs

What was the study designed to evaluate?

The study assessed the relationship between APOE variants and prostate cancer risk in Chinese men, and how these variants correlate with clinicopathological features.

Did APOE ε2/ε3 reduce overall prostate cancer risk?

No significant associations were observed between APOE variants and overall PCa risk or most clinical stratifications, but ε2/ε3 showed protection in specific PSA-defined contexts.

Which PSA-related subgroup showed a significant association with ε2/ε3?

Multivariable logistic regression found ε2/ε3 associated with reduced risk in the PSA “gray zone” (4–10 ng/mL) and inversely associated with high-PSA PCa (>20 ng/mL).

How were APOE genotypes related to Gleason score and PSA levels?

Serum PSA levels correlated positively with Gleason score in ε3/ε3 and ε3/ε4 carriers, but not in ε2/ε3 carriers, indicating genotype-dependent differences in disease grading signals.

Sep 23, 2026

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