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饮食诱导的体重减轻对结直肠癌生物标志物的影响:一项探索性研究(INTERCEPT)

The Impact of Diet-Induced Weight Loss on Biomarkers for Colorectal Cancer: An Exploratory Study (INTERCEPT).

作者信息

Beeken Rebecca J, Croker Helen, Heinrich Malgorzata, Obichere Austin, Finer Nicholas, Murphy Neil, Goldin Robert, Guppy Naomi J, Wilson Rose, Fisher Abigail, Steptoe Andrew, Gunter Marc J, Wardle Jane

机构信息

Department of Behavioural Science & Health, University College London, London, UK.

Leeds Institute of Health Sciences, University of Leeds, Leeds, UK.

出版信息

Obesity (Silver Spring). 2017 Nov;25 Suppl 2(Suppl 2):S95-S101. doi: 10.1002/oby.21984.

Abstract

OBJECTIVE

The aim of this study was to explore the potential effects of diet-induced weight loss on molecular biomarkers of colorectal cancer risk in serum and colorectal tissue.

METHODS

This single-arm exploratory study included 20 adults with BMI ≥ 30 kg/m completing an 8-week, complete, low-energy liquid diet. Pre- and postintervention anthropometric measurements, fasting blood draws, and endoscopic examinations to procure colorectal biopsies were performed. Fasting insulin, glucose, insulinlike growth factor 1 (IGF-1), C-reactive protein (CRP), and blood lipids were measured in serum, and tissue markers of apoptosis (M30), colonocyte proliferation (Ki-67), and insulin signaling (phospho-mTOR) were assessed using immunohistochemical staining.

RESULTS

Participants achieved substantial weight loss (mean = 13.56%). Mean concentrations of insulin, glucose, and cholesterol were significantly reduced (P < 0.05), but IGF-1 and CRP were not. Colorectal tissue expression of Ki-67 was significantly reduced (preintervention mean score = 7, postintervention mean score = 3.9, mean % change -43.8; P = 0.027). There were no significant changes in M30 or phospho-mTOR.

CONCLUSIONS

Weight loss in individuals with obesity was associated with improvements in insulin sensitivity and blood lipid profiles and a significant reduction in tissue Ki-67 expression. This is one of the first studies to demonstrate potential cancer-relevant changes in colorectal tissue following weight loss achieved through diet.

摘要

目的

本研究旨在探讨饮食诱导的体重减轻对血清和结肠直肠组织中结直肠癌风险分子生物标志物的潜在影响。

方法

这项单臂探索性研究纳入了20名BMI≥30kg/m²的成年人,他们完成了为期8周的完整低能量流质饮食。在干预前后进行人体测量、空腹采血以及内镜检查以获取结肠直肠活检样本。检测血清中的空腹胰岛素、葡萄糖、胰岛素样生长因子1(IGF-1)、C反应蛋白(CRP)和血脂,并使用免疫组织化学染色评估凋亡组织标志物(M30)、结肠细胞增殖标志物(Ki-67)和胰岛素信号标志物(磷酸化mTOR)。

结果

参与者体重显著减轻(平均减轻13.56%)。胰岛素、葡萄糖和胆固醇的平均浓度显著降低(P<0.05),但IGF-1和CRP未降低。Ki-67在结肠直肠组织中的表达显著降低(干预前平均评分为7,干预后平均评分为3.9,平均变化百分比为-43.8;P=0.027)。M30或磷酸化mTOR无显著变化。

结论

肥胖个体体重减轻与胰岛素敏感性和血脂状况改善以及组织Ki-67表达显著降低有关。这是首批证明通过饮食实现体重减轻后结肠直肠组织中存在潜在癌症相关变化的研究之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3a0/8515939/ce21a8c77a5d/OBY-25-S95-g001.jpg

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