Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, 6120 Executive Boulevard, Bethesda, Maryland 20852, USA.
Endocr Relat Cancer. 2013 Feb 18;20(1):151-60. doi: 10.1530/ERC-12-0229. Print 2013 Feb.
Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.
子宫内膜癌的风险受肥胖的强烈影响，但作用机制尚不清楚。瘦素和脂联素是由脂肪组织分泌的，据报道在细胞增殖、血管生成和胰岛素调节等致癌过程中发挥作用。在这项病例对照研究中，研究嵌套在骨折干预试验的乳腺和骨骼随访研究（n=15595）中，我们评估了绝经后妇女的血清瘦素、总脂联素和高分子量（HMW）脂联素与子宫内膜癌之间的关系。在 10 年的随访期间，发现了 62 例子宫内膜癌病例，并按年龄、地理位置、基线时禁食采血时间（1992-1993 年）和试验参与状态与 124 名对照进行匹配。通过 ELISA 测量脂联素和 C 肽。通过条件逻辑回归估计比值比（OR）和 95%置信区间（95%CI），将暴露分为三分位数（T）。多变量模型考虑了 C 肽、BMI（kg/m2）和雌二醇（E2）作为潜在的混杂因素。在调整 E2 和 C 肽后，子宫内膜癌风险与较高的瘦素水平显著相关（T3 与 T1 相比的 OR=2.96；95%CI，1.21-7.25；P 趋势<0.01）。进一步调整 BMI 后，估计值减弱，阳性趋势不再具有统计学意义（T3 与 T1 相比的 OR=2.11；95%CI，0.69-6.44；P 趋势=0.18）。脂联素或 HMW 脂联素与子宫内膜癌之间无显著关联。我们关于瘦素的研究结果表明，瘦素-BMI 轴可能通过雌激素驱动的增殖以外的机制增加子宫内膜癌的风险。在更大的前瞻性研究中继续探索这些途径可能有助于阐明观察到的肥胖-子宫内膜癌关联的机制。
