PDF(Pubmed)
Abstract：
Body shape phenotypes combining multiple anthropometric traits have been linked to postmenopausal breast cancer (BC). However, underlying biological pathways remain poorly understood. This study investigated to what extent the associations of body shapes with postmenopausal BC risk is mediated by biochemical markers. The study included 176,686 postmenopausal women from UK Biobank. Four body shape phenotypes were derived from principal component (PC) analysis of height, weight, body mass index, waist and hip circumferences, and waist-to-hip ratio (WHR). The four-way decomposition of the total effect was used to estimate mediation and interaction effects simultaneously as well as the mediated proportions. After 10.9 years median follow-up, 6,396 incident postmenopausal BC were diagnosed. There was strong evidence of positive associations between PC1 (general obesity) and PC2 (tall, low WHR), and BC risk. The association of PC1 with BC risk was positively mediated by testosterone and negatively by insulin-like growth factor-1 (IGF-1), with the overall proportion mediated (sum of the mediated interaction and pure indirect effect (PIE)) accounting for 11.4% (95% confidence intervals: 5.1 to 17.8%) and -12.2% (-20.5% to -4.0%) of the total effect, respectively. Small proportions of the association between PC2 and BC were mediated by IGF-1 (PIE: 2.8% (0.6 to 4.9%)), and sex hormone-binding globulin (SHBG) (PIE: -6.1% (-10.9% to -1.3%)). Our findings are consistent with differential pathways linking different body shapes with BC risk, with a suggestive mediation through testosterone and IGF-1 in the relationship of a generally obese body shape and BC risk, while IGF-1 and SHBG may mediate a tall/lean body shape-BC risk association.
摘要：
结合多种人体测量特征的体形表型与绝经后乳腺癌（BC）有关。然而,潜在的生物学途径仍然知之甚少。这项研究调查了生化标志物在多大程度上介导了体形与绝经后BC风险的关联。该研究包括来自英国生物银行的176,686名绝经后妇女。四种体型表型来自身高的主成分(PC)分析，体重,身体质量指数,腰围和臀围，腰臀比（WHR）。总效应的四向分解用于同时估计调解和相互作用效应以及介导的比例。经过10.9年的中位随访，诊断出6,396例绝经后BC。有强有力的证据表明PC1(一般肥胖)和PC2(高，低WHR),BC风险。PC1与BC风险的相关性是由睾酮介导的，而由胰岛素样生长因子-1(IGF-1)介导的。介导的总体比例（介导的相互作用和纯间接效应（PIE）的总和）占11.4％（95％置信区间：5.1至17.8％）和-12.2％（-20.5％至-4.0％）的总效应，分别。小比例的PC2和BC之间的关联由IGF-1介导（PIE：2.8％（0.6至4.9％）），和性激素结合球蛋白（SHBG）（PIE：-6.1％（-10.9％至-1.3％））。我们的发现与将不同的身体形态与BC风险联系起来的不同途径是一致的，通过睾酮和IGF-1在一般肥胖的体型和BC风险之间的关系中进行暗示性调解，而IGF-1和SHBG可能介导高/瘦体形-BC风险关联。
