散发性结直肠腺瘤患者正常黏膜中APC、β-catenin、E-钙粘蛋白和MSH2表达与饮食、生活方式和其他参与者特征的关系

Timothy D. Shu, R. Rutherford, M. Seabrook, E. Barry, R. Bostick
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引用次数: 0

摘要

Wnt通路和DNA错配修复蛋白的异常表达在结直肠癌发生过程中很常见。为了研究生活方式、饮食和其他参与者特征与这些蛋白质表达的横断面相关性,我们使用自动免疫组织化学和定量图像分析,测量了104例散发性结直肠腺瘤患者正常结直肠粘膜活检中APC、β-连环蛋白、E-钙粘蛋白和MSH2结直肠隐窝的表达。我们使用多变量通用线性模型来比较参与者特征类别的调整平均生物标志物表达。示例性发现包括,在女性中,与男性相比,整个隐窝、隐窝上部40%(分化区)和隐窝下部60%(增殖区)的平均APC表达分别高出322.9%(p<0.01)、296.7%(p<0.01。在饮酒量较高的参与者中,隐窝分化区的APC表达估计低15.9%(p=0.08)。在总肉类消费量较高的人中,整个隐窝和隐窝增殖区的β-连环蛋白表达估计分别高20.5%(p=0.07)和19.6%(p=0.06),隐窝分化区的MSH2表达估计低64.4%(p=0.010)。在体重指数较高的人群中,并且较高的酒精和肉类消费可能与散发性结直肠腺瘤患者正常出现的结直肠粘膜中的结直肠致癌途径蛋白的生物标志物不利相关,并支持更大规模研究中的进一步研究。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Associations of dietary, lifestyle, and other participant characteristics with APC, β-catenin, E-cadherin, and MSH2 expression in the normal mucosa of sporadic colorectal adenoma patients
Abnormal expression of Wnt pathway and DNA mismatch repair proteins is common during colorectal carcinogenesis. To investigate cross-sectional associations of lifestyle, dietary, and other participant characteristics with the expression of such proteins, we measured APC, β-catenin, E-cadherin, and MSH2 colorectal crypt expression in biopsies of normal-appearing colorectal mucosa from 104 sporadic colorectal adenoma patients using automated immunohistochemistry and quantitative image analysis. We used multivariable general linear models to compare adjusted mean biomarker expression across categories of participant characteristics. Example findings include that among women relative to men, mean APC expression in whole crypts, the upper 40% of crypts (differentiation zone), and the lower 60% of crypts (proliferation zone) was 322.9% higher (p<0.01), 296.7% higher (p<0.01), and 399.1% higher (p<0.01), respectively. Among participants with higher alcohol consumption, APC expression in the crypt differentiation zone was estimated to be 15.9% lower (p=0.08). Among those with higher total meat consumption, β-catenin expression in whole crypts and the crypt proliferation zone was estimated to be 20.5% higher (p=0.07) and 19.6% higher (p=0.06), respectively, and MSH2 expression in the crypt differentiation zone was estimated to be 64.4% lower (p=0.10). Among those with a higher body mass index, MSH2 expression in the crypt differentiation zone was estimated to be 87.5% lower (p=0.15). These pilot study findings suggest that being male, higher adiposity, and higher alcohol and meat consumption may be unfavorably associated with biomarkers of colorectal carcinogenesis pathway proteins in the normal-appearing colorectal mucosa of sporadic colorectal adenoma patients and support further investigation in larger studies.
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