脂联素、瘦素及可溶性瘦素受体对乳腺癌发病风险影响的人群研究

  目的  探讨脂联素、瘦素、可溶性瘦素受体（soluble leptin receptor，sOB-R）对女性绝经前后乳腺癌的单独或联合效应，为揭示肥胖与乳腺癌之间的分子机制提供证据。  方法  序贯纳入乳腺癌新发患者469例及同期按1∶1年龄频数匹配的469例健康女性为研究对象。采用问卷收集研究对象基线信息，并采用ELISA法检测血浆中脂联素、瘦素、sOB-R水平。采用多因素非条件logistic回归，并进一步按照腰臀比（waist-to-hip ratio，WHR）和体质量指数（body mass index，BMI）分层，分析观察指标对绝经前后乳腺癌发生风险的影响。  结果  本研究共纳入480例绝经前和458例绝经后女性。绝经前病例组249例，对照组231例，中位BMI分别为22.9 kg/m2、23.2 kg/m2，中位WHR分别为0.80、0.83。绝经后病例组220例，对照组238例，中位BMI分别为23.4 kg/m2、23.7 kg/m2；中位WHR分别为0.82、0.86。多因素logistics回归发现，模型校正前后，sOB-R、脂联素的升高与绝经前后的乳腺癌风险降低相关（P<0.05），而瘦素/可溶性瘦素受体比值（FLI） 、瘦素/脂联素比值（leptin/adiponectin，L/A）仅与绝经后乳腺癌的发生风险升高有关。进一步按WHR和BMI分层，脂联素、FLI与绝经后乳腺癌的关联在所有亚组仍有统计学意义。在体质量正常的中心型肥胖（18.5 kg/m2≤BMI<24 kg/m2且WHR≥0.85）妇女中，高L/A比值与绝经后乳腺癌风险增加有关。未发现瘦素与绝经前后乳腺癌的关联。  结论  sOB-R、脂联素水平降低，FLI、L/A升高的绝经后女性，sOB-R、脂联素水平降低的绝经前女性，乳腺癌的发生风险高。

Population-based Study of the Effects of Adiponectin,Leptin and Soluble Leptin Receptor on Risks for Breast Cancer

  Objective   To explore the individual or combined effects of adiponectin, leptin, and soluble leptin receptor (sOB-R) on risks for premenopausal and postmenopausal breast cancer, and to provide evidence for revealing the molecular mechanism between obesity and breast cancer.  Methods  469 newly-diagnosed breast cancer cases were sequentially recruited for the study and 469 age-frequency-matched healthy women were enrolled as the controls over the same period of time. The participant baseline information was collected with questionnaires, and plasmic levels of adiponectin, leptin and sOB-R were checked with ELISA. Multivariate unconditional logistic regression was conducted and the analyses were further stratified according to waist-to-hip ratio (WHR) and body mass index (BMI) to explore the effect of the indicators on the risks for premenopausal and postmenopausal breast cancer.  Results   A total of 480 premenopausal and 458 postmenopausal women were included in the study. Among the premenopausal subjects, 249 were breast cancer patients and 231 were controls. The median BMI was 22.9 kg/m2 and 23.2 kg /m2, respectively, and the median WHR was 0.80 and 0.83, respectively. Among the postmenopausal subjects, 220 were breast cancer patients and 238 were controls. The median BMI was 23.4 kg/m2 and 23.7 kg/m2, respectively, and the median WHR was 0.82 and 0.86, respectively. Multivariate logistic regression analysis showed that before and after model adjustment, the increase in sOB-R and adiponectin levels was correlated to reduced risks of premenopausal and postmenopausal breast cancer (P<0.05), while the increase in the leptin/sOB-R ratio (also known as free leptin index, FLI) and leptin/adiponectin (L/A) ratio was only correlated to increased risks of postmenopausal breast cancer. After further stratification by WHR and BMI, the association between adiponectin, FLI and postmenopausal breast cancer remained statistically significant in all subgroups. Among subjects with normal-BMI central obesity (18.5 kg/m2≤BMI<24 kg/m2 & WHR≥0.85) , higher L/A ratio was associated with an increased risk of postmenopausal breast cancer. No clear association between leptin and premenopausal and risks for postmenopausal breast cancer was found in the study.  Conclusion   Postmenopausal women with decreased levels of sOB-R and adiponectin, and increased FLI and L/A, and premenopausal women with decreased levels of sOB-R and adiponectin were found to be at high risks for breast cancer.