Adipokines linking obesity with colorectal cancer risk in postmenopausal women.
Adipokines linking obesity with colorectal cancer risk in postmenopausal women.
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DOI：
10.1158/0008-5472.can-11-2771
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发表时间：
2012-06-15
期刊：
影响因子：
11.2
通讯作者：
Rohan TE
中科院分区：
文献类型：
--
作者：
Ho GY;Wang T;Gunter MJ;Strickler HD;Cushman M;Kaplan RC;Wassertheil-Smoller S;Xue X;Rajpathak SN;Chlebowski RT;Vitolins MZ;Scherer PE;Rohan TE
肥胖与结直肠癌之间的机制关联仍不清楚。在这项研究中，我们研究了脂肪因子是否是结直肠癌的危险因素以及它们是否可能介导结直肠癌与肥胖的关系。在女性健康倡议绝经后妇女队列中的一项病例队列研究中，对 457 名结直肠癌病例和 841 名亚队列受试者的基线血浆样本进行了七种脂肪因子的检测：脂联素、瘦素、纤溶酶原激活剂抑制剂-1 (PAI-1)、抵抗素、肝细胞生长因子、白细胞介素-6 (IL-6) 和 TNF-α。之前测量的血清胰岛素和雌二醇值也可用于数据分析。在调整年龄、种族、吸烟、结肠镜检查史和雌激素水平后，低水平的抗炎脂联素和高水平的促炎瘦素、PAI-1和IL-6与结直肠癌风险增加相关，尽管在进一步调整胰岛素后只有瘦素仍然显着[HRs比较极端四分位数(HRQ4-Q1)，1.84； 95% CI，1.17–2.90]。中介分析表明，瘦素和胰岛素部分解释了腰围与结直肠癌之间的关联，并分别将其减弱了 25% 和 37%，其中胰岛素是显着的中介（P = 0.041）。我们的研究结果支持以下结论：参与炎症的脂肪因子与结直肠癌风险相关，但它们的作用可能主要由胰岛素介导，瘦素发挥独立作用。因此，高胰岛素血症和高瘦素血症可以部分解释绝经后妇女肥胖与结直肠癌的相关性。
Mechanistic associations between obesity and colorectal cancer remain unclear. In this study, we investigated whether adipokines are risk factors for colorectal cancer and whether they may mediate its association with obesity. In a case–cohort study nested within the Women’s Health Initiative cohort of postmenopausal women, baseline plasma samples from 457 colorectal cancer cases and 841 subcohort subjects were assayed for seven adipokines—adiponectin, leptin, plasminogen activator inhibitor-1 (PAI-1), resistin, hepatocyte growth factor, interleukin-6 (IL-6), and TNF-α. Serum insulin and estradiol values measured previously were also available for data analysis. After adjusting for age, race, smoking, colonoscopy history, and estrogen level, a low level of antiinflammatory adiponectin and high levels of proinflammatory leptin, PAI-1, and IL-6 were associated with increased colorectal cancer risk, though only leptin remained significant after further adjustment for insulin [HRs comparing extreme quartiles (HRQ4–Q1), 1.84; 95% CI, 1.17–2.90]. Mediation analyses showed that leptin and insulin partially explained the association between waist circumference and colorectal cancer and attenuated it by 25% and 37%, respectively, with insulin being a significant mediator (P = 0.041). Our findings support the conclusion that adipokines involved in inflammation are associated with colorectal cancer risk, but that their effects may be mediated mostly by insulin, with leptin exerting an independent effect. Hyperinsulinemia and hyperleptinemia may therefore partially explain the adiposity association with colorectal cancer in postmenopausal women.