Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, Maryland, USA.
SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
Endocr Relat Cancer. 2022 Jan 20;29(2):99-109. doi: 10.1530/ERC-21-0107.
Molecular mechanisms linking obesity to prostate cancer involve steroid hormone and insulin/insulin-like growth factor 1 (IGF1) pathways. We investigated the association of circulating serum markers (e.g. androgens and IGFs/IGFBPs) with BMI and in modifying the association of obesity with prostate cancer risk. Data and specimens for this nested case-control study are from the Prostate Cancer Prevention Trial, a randomized, placebo-controlled trial of finasteride for prostate cancer prevention. Presence or absence of cancer was determined by prostate biopsy. Serum samples were assayed for sex steroid hormone concentrations and IGF1 axis analytes. Logistic regression estimated odds ratio and 95% CIs for risk of overall, low-grade (Gleason 2-6), and high-grade (Gleason 7-10) cancers. We found significant associations between BMI with serum steroids and IGFs/IGFBPs; the IGF1 axis was significantly associated with several serum steroids. Serum steroid levels did not affect the association of BMI with prostate cancer risk; however, IGFBP2 and IGFs modified the association of obesity with low- and high-grade disease. While serum steroids and IGFs/IGFBPs are associated with BMI, only the IGF1 axis contributed to obesity-related prostate cancer risk. Understanding the biological mechanisms linking obesity to prostate cancer risk as it relates to circulating serum markers will aid in developing effective prostate cancer prevention strategies and treatments.
肥胖与前列腺癌相关的分子机制涉及甾体激素和胰岛素/胰岛素样生长因子 1（IGF1）途径。我们研究了循环血清标志物（如雄激素和 IGFs/IGFBPs）与 BMI 的相关性，以及它们在修饰肥胖与前列腺癌风险的相关性中的作用。这项巢式病例对照研究的数据和标本来自前列腺癌预防试验（Prostate Cancer Prevention Trial），这是一项针对前列腺癌预防的非那雄胺随机、安慰剂对照试验。癌症的存在或不存在通过前列腺活检确定。血清样本用于检测性激素浓度和 IGF1 轴分析物。逻辑回归估计了总体、低级别（Gleason 2-6）和高级别（Gleason 7-10）癌症的风险比和 95%置信区间。我们发现 BMI 与血清类固醇和 IGFs/IGFBPs 之间存在显著相关性；IGF1 轴与几种血清类固醇显著相关。血清类固醇水平不影响 BMI 与前列腺癌风险的相关性；然而，IGFBP2 和 IGFs 改变了肥胖与低级别和高级别疾病的相关性。虽然血清类固醇和 IGFs/IGFBPs 与 BMI 相关，但只有 IGF1 轴与肥胖相关的前列腺癌风险有关。了解肥胖与前列腺癌风险相关的生物学机制，以及它们与循环血清标志物的关系，将有助于制定有效的前列腺癌预防策略和治疗方法。
