Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Center for Lipid Metabolomics, Divisions of Preventive Medicine and Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Am J Epidemiol. 2018 Apr 1;187(4):705-716. doi: 10.1093/aje/kwx250.
Chronic inflammation may be a risk factor for the development and progression of breast cancer, yet it is unknown which inflammatory biomarkers and pathways are especially relevant. The present study included 27,071 participants (mean age = 54.5 years) in the Women's Health Study who were free of cancer and cardiovascular disease at enrollment (1992-1995), with baseline measures of 4 inflammatory biomarkers: high-sensitivity C-reactive protein, fibrinogen, N-acetyl side-chains of acute phase proteins, and soluble intercellular adhesion molecule-1. We used Cox proportional hazards regression models to evaluate associations between baseline concentrations of biomarkers and incident breast cancer, and adjusted for baseline and time-varying factors such as age and body mass index. Self-reported invasive breast cancer was confirmed against medical records for 1,497 incident cases (90% postmenopausal). We observed different patterns of risk depending on the inflammatory biomarker. There was a significant direct association between fibrinogen and breast cancer risk (for quintile 5 vs. quintile 1, adjusted hazard ratio = 1.25, 95% confidence interval: 1.03, 1.51; P for trend = 0.01). In contrast, soluble intercellular adhesion molecule-1 was inversely associated with breast cancer (for quintile 5 vs. quintile 1, adjusted hazard ratio = 0.79, 95% confidence interval: 0.66, 0.94; P for trend = 0.02). N-acetyl side-chains of acute phase proteins and high-sensitivity C-reactive protein were not associated with breast cancer. The complex association of chronic inflammation and breast cancer may be considered when formulating anti-inflammatory cancer prevention or intervention strategies.
慢性炎症可能是乳腺癌发生和发展的一个危险因素,但目前尚不清楚哪些炎症生物标志物和途径与乳腺癌特别相关。本研究纳入了 27071 名参与者(平均年龄为 54.5 岁),这些参与者在入组时(1992-1995 年)无癌症和心血管疾病病史,并在基线时测量了 4 种炎症生物标志物:高敏 C 反应蛋白、纤维蛋白原、急性相蛋白的 N-乙酰侧链和可溶性细胞间黏附分子-1。我们使用 Cox 比例风险回归模型评估了生物标志物基线浓度与乳腺癌发病之间的关联,并对年龄和体重指数等基线和时变因素进行了调整。通过医疗记录对 1497 例乳腺癌发病病例(90%为绝经后)进行了自我报告的浸润性乳腺癌的确认。我们观察到不同的炎症生物标志物与乳腺癌风险之间存在不同的关联模式。纤维蛋白原与乳腺癌风险之间存在显著的直接关联(第 5 五分位与第 1 五分位相比,调整后的风险比=1.25,95%置信区间:1.03,1.51;趋势 P 值=0.01)。相比之下,可溶性细胞间黏附分子-1与乳腺癌呈负相关(第 5 五分位与第 1 五分位相比,调整后的风险比=0.79,95%置信区间:0.66,0.94;趋势 P 值=0.02)。急性相蛋白的 N-乙酰侧链和高敏 C 反应蛋白与乳腺癌无关。在制定抗炎性癌症预防或干预策略时,可以考虑慢性炎症与乳腺癌之间的复杂关联。