Department of Public Health, College of Medicine, Fu-Jen Catholic University, No. 510, Jhongjheng Road, Sinjhuang 242, Taipei, Taiwan, ROC.
Breast Cancer Res Treat. 2010 Oct;123(3):869-76. doi: 10.1007/s10549-010-0792-4. Epub 2010 Feb 23.
Adipocytokine resistin is a member of the newly discovered family of cysteine-rich protein. Recent data suggest that macrophages are a major source of human resistin. Given the obesity-breast cancer link and convergence of adipocyte and macrophage function, resistin may provide unique insight into links between obesity, inflammation, and breast cancer risk in humans. We conducted a hospital-based case-control study to evaluate whether plasma resistin levels were associated with breast cancer risk in women. We also examined the modification effect of estrogen exposures on the resistin-breast cancer link. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 380 incident cases with breast cancer and 760 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2008. Plasma levels of resistin were measured by enzyme immunoassay. Cumulative exposure to estrogens were estimated according to the age at menarche and age at enrollment for premenopausal women and age at menarche and age at menopause for postmenopausal women. Cases with breast cancer had significantly elevated resistin concentrations as compared with control subjects. Compared with those in the lowest quartile, the adjusted odds ratios of breast cancer for women in the second, third, and highest quartiles were 1.48 [95% confidence interval (CI) = 0.65-3.38], 1.76 (95% CI = 1.00-4.73), and 2.08 (95% CI = 1.04-3.85), respectively. Furthermore, the biological gradient of breast cancer risk by plasma resistin levels remained after adjustment for measures of adiposity. The dose-dependent relationship of resistin levels with breast cancer risk was notably pronounced among women with excess exposure to estrogens. Adipocytokine resistin may have an adiposity-independent role in breast carcinogenesis. Mechanistic studies to fully elucidate the mechanisms underlying resistin's effects should be pursued in future investigations.
脂联素抵抗素是新发现的富含半胱氨酸蛋白家族的成员。最近的数据表明，巨噬细胞是人类抵抗素的主要来源。鉴于肥胖与乳腺癌之间的联系以及脂肪细胞和巨噬细胞功能的趋同，抵抗素可能为肥胖、炎症与乳腺癌风险之间的联系提供独特的见解。我们进行了一项基于医院的病例对照研究，以评估血浆抵抗素水平是否与女性乳腺癌风险相关。我们还研究了雌激素暴露对抵抗素与乳腺癌联系的修饰作用。2004 年至 2008 年间，在台北三军总医院接受健康检查的 380 例乳腺癌新发病例和 760 例对照者入组前，通过问卷调查、人体测量和采血，收集了相关信息。采用酶联免疫吸附法测定血浆抵抗素水平。根据绝经前女性的初潮年龄和入组年龄以及绝经后女性的初潮年龄和绝经年龄，估算雌激素的累积暴露量。与对照组相比，乳腺癌病例的抵抗素浓度显著升高。与处于最低四分位的女性相比，第二、第三和最高四分位的女性患乳腺癌的调整比值比（OR）分别为 1.48（95%置信区间[CI] = 0.65-3.38）、1.76（95%CI = 1.00-4.73）和 2.08（95%CI = 1.04-3.85）。此外，在调整了肥胖指标后，血浆抵抗素水平与乳腺癌风险之间的生物学梯度仍然存在。抵抗素水平与乳腺癌风险的剂量依赖性关系在雌激素过量暴露的女性中尤为明显。脂联素抵抗素可能在乳腺癌发生中具有与肥胖无关的作用。未来的研究应该进行机制研究，以充分阐明抵抗素作用的机制。
