PO.PR01.01 · 预防研究
载脂蛋白E基因与黑人男性PSA水平
Apolipoprotein E gene & PSA levels in Black men
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景/意义：与其他种族和族裔群体的男性相比，前列腺癌（Pca）在非裔美国（AA）男性中更为常见。载脂蛋白E（APOE）在脂质代谢中发挥关键作用，促进胆固醇和脂质转运，其异构体可能影响癌症进展。前列腺特异性抗原（PSA）是Pca的一种生物标志物，PSA水平升高可能预示患者存在Pca。我们的研究探讨这一差异背后的遗传因素，特别聚焦于APOE基因及其在前列腺癌细胞增殖中的作用。在本研究中，我们旨在对APOE基因座进行深入分析，检查异构体分化及其与非裔美国男性PSA升高的关系。
方法：使用线性和逻辑回归以及基于单倍型的建模（R包haplostats）进行了APOE SNP水平（rs429358、rs7412、rs440446）和单倍型水平分析。模型校正了年龄、西非遗传祖源（WAA）、维生素D、病例-对照状态以及PSA（在适用时）。在质量控制后，对来自华盛顿特区（N=648）、南卡罗来纳州哥伦比亚（N=632）和喀麦隆西非（Bamileke，N=90）的1,370名西非祖源男性分别进行了分析。
结果：在AA男性中，PSA水平由年龄（beta = 0.050，p = 1.39 × 10⁻⁵）和病例状态（beta = 0.52，p < 1 × 10⁻¹²）强烈预测。APOE单倍型与PSA（E4：p = 0.80；E2：p = 0.36）或前列腺癌状态（逻辑回归：E4 p = 0.71，E2 p = 0.58）均无关联。维生素D（p = 0.12）和WAA（p = 0.25）也是非显著的预测因子。在来自喀麦隆西非的男性中，我们观察到一个名义上的关联，提示E2单倍型携带者的PSA更高（beta = 1.03，p = 0.045），但在AA中未观察到这一现象。E4（p = 0.69）或E3未检测到显著关联。在合并分析中，APOE SNPs和单倍型与PSA（E4：p = 0.93；E2：p = 0.67）或病例-对照状态（等位基因检验：所有SNPs的p > 0.50）均无显著关联。在所有模型中，年龄（p < 2 × 10⁻⁹）和PSA（p < 6 × 10⁻¹⁵）仍是前列腺癌状态最强的预测因子。
结论与意义：在三个总计超过1,300名黑人男性的群体中，包括E2、E3和E4单倍型在内的APOE遗传变异均未显著预测PSA水平或前列腺癌风险。在分层分析中观察到的关联未能复现，也未能在合并分析中成立。需要更多研究来确认APOE在这些人群的前列腺癌病因或PSA调控中是否发挥具有生物学意义的作用。
资助致谢：本研究由美国癌症协会癌症研究多样性机构发展基金885016资助的健康公平研究职业发展计划支持。
查看英文原文 English abstract
Background/Significance: Prostate cancer (Pca) is more prevalent among African American (AA) men compared to men of other racial and ethnic groups. Apolipoprotein E (APOE) plays a critical role in lipid metabolism and facilitates cholesterol and lipid transport, with its isoforms potentially impacting cancer progression. Prostate-specific antigen (PSA) is a biomarker of Pca and elevated PSA levels may predict the presence of Pca in patients. Our study investigates the genetic factors underlying this disparity, with a specific focus on the APOE gene and its role in prostate cancer cell proliferation. In this study, we aim to conduct an in-depth analysis of the APOE gene locus, examining isoform differentiation and its relationship to PSA elevation in African American men.
Methods: APOE SNP-level (rs429358, rs7412, rs440446) and haplotype-level analyses were performed using linear and logistic regression and haplotype-based modeling (R package haplostats). Models adjusted for age, West African genetic ancestry (WAA), vitamin D, case-control status, and PSA when applicable. Analyses were conducted separately after quality control in 1,370 men of west African ancestry from Washington DC (N=648), Columbia, SC (N=632) and Cameroon west Africa (Bamileke, N=90).
Results: Among AA men, PSA levels were strongly predicted by age (beta = 0.050, p = 1.39 × 10⁻⁵) and case status (beta = 0.52, p < 1 × 10⁻¹²). APOE haplotypes demonstrated no association with PSA (E4: p = 0.80; E2: p = 0.36) or prostate cancer status (logistic regression: E4 p = 0.71, E2 p = 0.58). Vitamin D (p = 0.12) and WAA (p = 0.25) were also non-significant predictors. Among men from Cameroon west Africa, we observed a nominal association suggesting higher PSA in E2 haplotype carriers (beta = 1.03, p = 0.045), but this was not observed among AAs. No significant associations were detected for E4 (p = 0.69) or E3. In the combined analysis, APOE SNPs and haplotypes were not significantly associated with PSA (E4: p = 0.93; E2: p = 0.67) or case-control status (allelic tests: p > 0.50 for all SNPs). Across all models, age (p < 2 × 10⁻⁹) and PSA (p < 6 × 10⁻¹⁵) remained the strongest predictors of prostate cancer status.
Conclusion and Implications: Across three groups totaling more than 1,300 Black men, APOE genetic variation including the E2, E3, and E4 haplotypes did not significantly predict PSA levels or prostate cancer risk. Associations observed in the stratified analyses were not replicated and did
not withstand combined analysis. More studies are needed to confirm if APOE plays a biologically meaningful role in prostate cancer etiology or PSA regulation in these populations.
Acknowledgment of Funding: This research is supported by the Health Equity Research Career Advancement Program funded by the American Cancer Society's Diversity in Cancer Research Institutional Development Grant 885016.
利益披露 Disclosure
L. J. Jones, None..
J. Johnson, None..
D. Lewis, None..
L. K. Brown, None..
R. Kittles, None.