PO.BCS01.16 · 生物信息与计算

通过多基因评分对糖尿病和非糖尿病男性进行前列腺癌风险分层

Prostate cancer risk stratification by polygenic score in diabetic and non-diabetic men

编号 2717 展板 10 时间 4/20 02:00–05:00 区域 Section 2 主讲 Gukjin Lee, PhD

分会场 Integration of Clinical and Research Data

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作者与单位 Authors & Affiliations

Gukjin Lee¹, Sang-Hyuk Jung², Jonghyun Lee³, Ki Won Moon⁴, Jae-Seung Yun⁵, Dokyoon Kim³

¹Bucheon St. Mary's Hospital, The Catholic University of Korea Bucheon, Seoul, Korea, Republic of,²Department of Medical Informatics,, Kangwon National University College of Medicine, Chuncheon, Korea, Republic of,³Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA,⁴Division of Rheumatology, Department of Internal Medicine, Kangwon National University College of Medicine, Chuncheon, Korea, Republic of,⁵St. Vincent’s Hospital, College of Medicine, the Catholic University of Korea, Seoul, Korea, Republic of

摘要 Abstract

中文摘要

背景:2型糖尿病(T2DM)与前列腺癌(PrCa)风险呈负相关。然而,前列腺癌的多基因风险评分(PRS)能否有效地对T2DM男性进行风险分层,仍不明确。本研究旨在评估PrCa PRS能否独立于T2DM状态预测PrCa风险。方法:我们分析了UK Biobank和Penn Medicine Biobank中超过140,000名男性的数据。使用一项大规模全基因组关联研究的汇总统计数据构建了PrCa PRS。使用Cox比例风险模型评估PRS与新发PrCa之间的关联,校正相关协变量并检验与T2DM状态的交互作用。此外,分析了性激素和胰岛素样生长因子-1(IGF-1)水平,以探索潜在的中介因素。结果:T2DM与PrCa发病率降低相关。IGF-1水平在糖尿病和非糖尿病男性中均与PrCa风险正相关,而性激素水平在T2DM男性中未显示显著关联。无论T2DM状态如何,PRS均与PrCa风险显著相关(P < 0.001)。PRS极高类别的男性PrCa风险最高,尤其是在无T2DM的男性中。校正睾酮和IGF-1水平并未减弱PRS与PrCa之间的关联。结论:PrCa PRS能够有效地对有糖尿病和无糖尿病男性的前列腺癌风险进行分层,强调了遗传易感性作为一个稳健、独立的风险因素。鉴于T2DM患者的基线IGF-1水平显著较低,IGF-1可能部分解释了该人群中观察到的PrCa风险降低。

查看英文原文 English abstract

Background: Type 2 diabetes mellitus (T2DM) has been inversely associated with prostate cancer (PrCa) risk. However, it remains unclear whether a polygenic risk score (PRS) for PrCa can effectively stratify risk among men with T2DM. This study aimed to assess whether a PrCa PRS could predicts PrCa risk independently of T2DM status. Methods: We analyzed data from over 140,000 men in the UK Biobank and Penn Medicine Biobank. A PrCa PRS was constructed using summary statistics from a large-scale genome-wide association study. Cox proportional hazards models were used to evaluate the association between PRS and incident PrCa, adjusting for relevant covariates and testing for interaction by T2DM status. Additionally, sex hormones and insulin-like growth factor-1 (IGF-1) levels were analyzed to explore potential mediators. Results: T2DM was associated with a reduced incidence of PrCa. IGF-1 levels were positively associated with PrCa risk in both diabetic and non-diabetic men, while sex hormone levels showed no significant association in men with T2DM. PRS was significantly associated with PrCa risk regardless of T2DM status ( P < 0.001). Men in the very high PRS category had the highest PrCa risk, particularly among those without T2DM. Adjusting for testosterone and IGF-1 levels did not attenuate the association between PRS and PrCa. Conclusions: PrCa PRS effectively stratifies prostate cancer risk in men both with and without diabetes, underscoring genetic susceptibility as a robust, independent risk factor. Given the significantly lower baseline IGF-1 levels in T2DM patients, IGF-1 might partially explain the reduced PrCa risk observed in this population.

利益披露 Disclosure

G. Lee, None.. S. Jung, None.. J. Lee, None.. K. Moon, None.. J. Yun, None.. D. Kim, None.

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