Effects of High-Order Interactions among IGFBP-3 Genetic Polymorphisms, Body Mass Index and Soy Isoflavone Intake on Breast Cancer Susceptibility.
Effects of High-Order Interactions among IGFBP-3 Genetic Polymorphisms, Body Mass Index and Soy Isoflavone Intake on Breast Cancer Susceptibility.
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IGFBP-3基因多态性、体重指数和大豆异黄酮摄入量之间的高阶相互作用对乳腺癌易感性的影响
DOI：
10.1371/journal.pone.0162970
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Li J
中科院分区：
文献类型：
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作者：
Wang Q;Liu L;Li H;Tao P;Qi Y;Li J
背景IGF-1和IGFBP-3的多态性和环境因素可能共同影响胰岛素样生长因子（IGF）水平，从而影响乳腺癌（BC）的风险。然而，很少有研究调查这些变量之间的高阶相互作用。方法收集2010年10月至2012年7月期间277例新诊断的乳腺癌患者和277例对照。我们收集了每个参与者的人口统计学特征，饮食摄入量和血液样本。然后对IGF-1 rs 1520220和IGFBP-3 rs 2854744进行基因分型。采用非条件Logistic回归（ULR）、广义多因素降维（GMDR）和分类回归树（CART）方法相结合的多分析策略，系统地研究了两个单核苷酸多态性（SNPs）、体重指数（BMI）和每日大豆摄入量（DISI）对BC易感性的相互作用。结果在GMDR分析中，在总体和绝经后妇女中确定了BMI、DISI和SNP rs 2854744之间的高阶交互作用。我们还发现，随着暴露因素的增加，即携带rs 2854744 AA基因型、DISI <9.85 mg/d和BMI ≥24 kg/m2，对BC风险有显著的剂量效应（P趋势<0.05）。同样，在CART分析中，与BMI<24 kg/m2、DISI<9.85 mg/d和rs 2854744 CC+CA基因型的个体相比，携带rs 2854744 AA基因型的个体BC风险显著增加，BMI<24 kg/m2和DISI<9.85 mg/d BMI≥ 24 kg/m2和DISI<9.85 mg/d者的OR = 1.95，95%CI：1.03-3.69（OR = 2.13，95%CI：1.00-4.51）。在绝经后妇女中观察到类似的相互作用效应。结论IGFBP-3 rs 2854744 AA基因型、BMI≥ 24 kg/m2和DISI<9.85 mg/d与乳腺癌风险增加存在高度交互作用，尤其是在绝经后妇女中。
Background Polymorphisms of IGF-1 and IGFBP-3 and environmental factors may work together to influence insulin-like growth factor (IGF) levels and thus breast cancer (BC) risk. However, very few studies have investigated high-order interactions among these variables. Methods A total of 277 newly diagnosed BC cases and 277 controls were recruited between October 2010 and July 2012. We collected each participant's demographic characteristics, dietary intake, and blood sample. IGF-1 rs1520220 and IGFBP-3 rs2854744 were then genotyped. A multi-analytic strategy combining unconditional logistic regression (ULR), generalized multifactor dimensionality reduction (GMDR), and classification and regression tree (CART) approaches was applied to systematically identify the interactions of the two single nucleotide polymorphisms (SNPs), body mass index (BMI), and daily intake of soy isoflavone (DISI) on BC susceptibility. Results In GMDR analyses, high-order interactions among BMI, DISI, and SNP rs2854744 were identified among overall and postmenopausal women. We also found significant dosage effects on BC risk with an increasing number of exposure factors, namely carrying the rs2854744 AA genotype, DISI <9.85 mg/day, and BMI ≥24 kg/m2 (P trend<0.05). Similarly, in CART analyses, compared with individuals having BMI<24kg/m2, DISI<9.85 mg/day, and the rs2854744 CC+CA genotype, BC risk increased significantly for those carrying the rs2854744 AA genotype, with BMI<24 kg/m2 and DISI<9.85 mg/day (OR = 1.95, 95%CI: 1.03–3.69), and also for those with BMI≥24kg/m2 and DISI<9.85 mg/day (OR = 2.13, 95%CI: 1.00–4.51). Similar interaction effects were observed among postmenopausal women. Conclusions This study suggests high-order interactions of the IGFBP-3 rs2854744 AA genotype, BMI≥24kg/m2, and DISI<9.85 mg/day on increased BC risk, particularly among postmenopausal women.
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