Adiposity, Inflammation, and Breast Cancer Pathogenesis in Asian Women.
Adiposity, Inflammation, and Breast Cancer Pathogenesis in Asian Women.
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DOI：
10.1158/1940-6207.capr-17-0283
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发表时间：
2018-04
期刊：
影响因子：
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通讯作者：
Dannenberg AJ
中科院分区：
文献类型：
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作者：
Iyengar NM;Chen IC;Zhou XK;Giri DD;Falcone DJ;Winston LA;Wang H;Williams S;Lu YS;Hsueh TH;Cheng AL;Hudis CA;Lin CH;Dannenberg AJ
肥胖与乳房白色脂肪组织(WAT)炎症、雌激素生物合成酶、芳香酶水平升高以及易患乳腺癌的全身变化有关。在体重指数(BMI)不能准确评估肥胖和癌症风险的亚洲人群中，我们研究了WAT炎症及其相关的全身影响是否与体脂水平相关。我们还调查了生物学差异是否可以解释亚洲和西方国家绝经前雌激素受体(ER)阳性乳腺癌的更大比例。乳房水和空腹血是从接受乳房切除术治疗乳腺癌的台湾妇女中前瞻性地采集的。使用生物电阻抗分析在亚组中测量身体成分。WAT炎症的定义是乳房存在冠状结构，这些结构由死亡或濒临死亡的脂肪细胞组成，周围有巨噬细胞。研究结果与美国高加索女性进行了比较。在台湾队列(n=72)中，31名(43%)女性出现乳房水炎，并与BMI升高(P<；0.01)和体脂(P<；0.01)、C-反应蛋白(P=0.02)、甘油三酯(P<；0.01)、胰岛素抵抗评分(P=0.04)和较低的高密度脂蛋白(P<；0.01)水平相关。ER+肿瘤与其他亚型相比体脂较多(P=0.03)。与美国高加索人(n=267)相比，台湾女性的乳房脂肪细胞较大，尽管调整了BMI和绝经状态后的BMI较低(P=0.01)。与肥胖增加和代谢障碍相关的亚临床炎症状态可能与亚洲女性乳腺癌的发病机制有关。
Obesity is associated with white adipose tissue (WAT) inflammation in the breast, elevated levels of the estrogen biosynthetic enzyme, aromatase, and systemic changes that predispose to breast cancer development. We examined whether WAT inflammation and its associated systemic effects correlate with body fat levels in an Asian population where body mass index (BMI) is not an accurate assessment of obesity and cancer risk. We also investigated whether biologic differences could account for the greater proportion of premenopausal estrogen receptor (ER)-positive breast cancer in Asian versus western countries. Breast WAT and fasting blood were prospectively collected from Taiwanese women undergoing mastectomy for breast cancer treatment. Body composition was measured in a subgroup using bioelectrical impedance analysis. WAT inflammation was defined by the presence of crown-like structures of the breast which are composed of dead or dying adipocytes surrounded by macrophages. Findings were compared with US Caucasian women. In the Taiwanese cohort (n=72), breast WAT inflammation was present in 31 (43%) women and was associated with elevated BMI (P<0.01) and increased levels of body fat (P<0.01), C-reactive protein (P=0.02), triglycerides (P<0.01), insulin resistance scores (P=0.04), and lower HDL cholesterol (P<0.01). ER+ tumors were associated with greater body fat versus other subtypes (P=0.03). Compared with US Caucasians (n=267), Taiwanese women had larger breast adipocytes despite lower BMI after adjusting for BMI and menopausal status (P=0.01). A subclinical inflammatory state associated with increased adiposity and metabolic dysfunction could contribute to breast cancer pathogenesis in Asian women.