绝经前和绝经后女性正常乳腺组织中炎症标志物表达与乳腺X线密度之间的关联。
Association between expression of inflammatory markers in normal breast tissue and mammographic density among premenopausal and postmenopausal women.
作者信息
Hanna Mirette, Dumas Isabelle, Orain Michèle, Jacob Simon, Têtu Bernard, Sanschagrin François, Bureau Alexandre, Poirier Brigitte, Diorio Caroline
机构信息
1Oncology Axis, Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec, Université Laval, Quebec, Canada 2Faculté de médecine, Université Laval, Quebec, Canada 3Centre des Maladies du Sein Deschênes-Fabia, Hôpital du Saint-Sacrement, Quebec, Canada 4Pathology and Molecular Biology Services, Hôpital Saint-Sacrement, CHU de Québec, Université Laval, Quebec, Canada 5Centre de recherche sur le cancer de l'Université Laval, Quebec, Canada 6Centre de Recherche de l'Institut Universitaire en Santé Mentale de Québec, Université Laval, Quebec, Canada.
出版信息
Menopause. 2017 May;24(5):524-535. doi: 10.1097/GME.0000000000000794.
OBJECTIVE
Inflammatory markers may be associated with breast cancer risk. We assessed the association between expression levels of proinflammatory (interleukin 6, tumor necrosis factor-α, C-reactive protein, cyclooxygenase 2, leptin, serum amyloid A1, interleukin 8, and signal transducer and activator of transcription 3) and anti-inflammatory markers (transforming growth factor-β, interleukin 10, and lactoferrin) in normal breast tissue with mammographic density, a strong breast cancer risk indicator, among 163 breast cancer patients.
METHODS
The expression of inflammatory markers was visually evaluated on immunohistochemistry stained slides. The percent mammographic density (PMD) was estimated by a computer-assisted method in the contralateral cancer-free breast. We used generalized linear models to estimate means of PMD by median expression levels of the inflammatory markers while adjusting for age and waist circumference.
RESULTS
Higher expression levels (above median) of the proinflammatory marker interleukin 6 were associated with higher PMD among all women (24.1% vs 18.5%, P = 0.007). Similarly, higher expression levels (above median) of the proinflammatory markers (interleukin 6, tumor necrosis factor-α, C-reactive protein, and interleukin 8) were associated with higher PMD among premenopausal women (absolute difference in the PMD of 8.8% [P = 0.006], 7.7% [P = 0.022], 6.7% [P = 0.037], and 16.5% [P = 0.032], respectively). Higher expression levels (above median) of the anti-inflammatory marker transforming growth factor-β were associated with lower PMD among all (18.8% vs 24.3%, P = 0.005) and postmenopausal women (14.5% vs 20.7%, P = 0.013).
CONCLUSIONS
Our results provide support for the hypothesized role of inflammatory markers in breast carcinogenesis through their effects on mammographic density. Inflammatory markers could be targeted in future breast cancer prevention interventions.
目的
炎症标志物可能与乳腺癌风险相关。我们评估了163例乳腺癌患者正常乳腺组织中促炎标志物（白细胞介素6、肿瘤坏死因子-α、C反应蛋白、环氧合酶2、瘦素、血清淀粉样蛋白A1、白细胞介素8以及信号转导和转录激活因子3）和抗炎标志物（转化生长因子-β、白细胞介素10和乳铁蛋白）的表达水平与乳腺X线密度之间的关联，乳腺X线密度是一个强有力的乳腺癌风险指标。
方法
在免疫组织化学染色切片上通过视觉评估炎症标志物的表达。通过计算机辅助方法估计对侧未患癌乳腺的乳腺X线密度百分比（PMD）。我们使用广义线性模型，在调整年龄和腰围的同时，根据炎症标志物的中位数表达水平估计PMD的均值。
结果
在所有女性中，促炎标志物白细胞介素6的较高表达水平（高于中位数）与较高的PMD相关（24.1%对18.5%，P = 0.007）。同样，在绝经前女性中，促炎标志物（白细胞介素6、肿瘤坏死因子-α、C反应蛋白和白细胞介素8）的较高表达水平（高于中位数）与较高的PMD相关（PMD的绝对差异分别为8.8% [P = 0.006]、7.7% [P = 0.022]、6.7% [P = 0.037]和16.5% [P = 0.032]）。抗炎标志物转化生长因子-β的较高表达水平（高于中位数）在所有女性（18.8%对24.3%，P = 0.005）和绝经后女性（14.5%对20.7%，P = 0.013）中与较低的PMD相关。
结论
我们的结果支持了炎症标志物通过对乳腺X线密度的影响在乳腺癌发生中所起的假设作用。炎症标志物可能成为未来乳腺癌预防干预的靶点。
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