PDF(Pubmed)
Abstract：
Obesity is a risk factor for postmenopausal breast cancer (BC), and evidence suggests a role for adiponectin in the relationship between obesity and BC. We investigated whether adiponectin or other biomarkers mediate the effect of body mass index (BMI) on postmenopausal BC risk in a cohort study nested in the IBIS-II Prevention Trial. We measured adiponectin, leptin, IGF-I, IGFBP-1, high-sensitivity C-reactive protein, glycemia, insulin, HOMA-IR index, and SHBG in baseline and 12-month serum samples from 123 cases and 302 matched controls in the placebo arm of the IBIS-II Prevention trial. We conducted the main mediation analysis considering baseline BMI as an exposure and the 12-month adiponectin increase as a mediator after adjustment for the Tyrer-Cuzick score and the lipid-lowering medications/supplements use. In the multivariable Cox model, both the 12-month adiponectin increase (HR, 0.60; 95%CI, 0.36-1.00) and BMI were associated with BC risk (HR, 1.05; 95%CI, 1.00-1.09), with a 40% reduction in women with a 12-month increase in adiponectin. A significantly higher cumulative hazard of BC events was observed in obese women (BMI > 30) with decreased adiponectin (p = 0.0087). No mediating effect of the adiponectin increase on the total effect of BMI on BC risk was observed (natural indirect effect: HR, 1.00; 95%CI, 0.98-1.02). Raising adiponectin levels might be an attractive target for postmenopausal BC prevention.
摘要：
肥胖是绝经后乳腺癌（BC）的危险因素，有证据表明脂联素在肥胖和BC之间的关系中起作用。在一项纳入IBIS-II预防试验的队列研究中，我们调查了脂联素或其他生物标志物是否介导体重指数（BMI）对绝经后BC风险的影响。我们测量了脂联素，瘦素,IGF-I,IGFBP-1,高敏C反应蛋白,血糖，胰岛素，HOMA-IR指数，在IBIS-II预防试验的安慰剂组中，来自123例病例和302个匹配对照的基线和12个月血清样本中的SHBG。在调整Tyrer-Cuzick评分和降脂药物/补充剂使用后，我们进行了主要的中介分析，将基线BMI作为暴露量和12个月脂联素升高作为中介。在多变量Cox模型中，这两个12个月的脂联素增加(HR，0.60；95CI，0.36-1.00）和BMI与BC风险相关（HR，1.05;95CI,1.00-1.09),12个月增加脂联素的女性减少了40％。在脂联素降低的肥胖女性（BMI>30）中观察到BC事件的累积风险明显更高（p=0.0087）。未观察到脂联素增加对BMI对BC风险的总影响的中介作用（自然间接作用：HR，1.00；95CI，0.98-1.02）。提高脂联素水平可能是预防绝经后BC的一个有吸引力的目标。
