Prospective multicenter cohort study of estrogen and insulin-like growth factor system in BRCA mutation carriers.
Prospective multicenter cohort study of estrogen and insulin-like growth factor system in BRCA mutation carriers.
复制标题
BRCA 突变携带者雌激素和胰岛素样生长因子系统的前瞻性多中心队列研究。
DOI：
10.1007/s10552-015-0601-9
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Mersereau,JE
中科院分区：
文献类型：
--
作者：
Kim,J;Johnson,L;Skrzynia,C;Buchanan,A;Gracia,C;Mersereau,JE
BRCA 1/2相关性肿瘤的主要临床特征包括与雌激素和代谢结果的相关性。我们的目的是评估血清雌二醇（E2）和胰岛素样生长因子1（IGF-1）水平作为BRCA 1/2突变携带者和高风险，BRCA-negative controls.MethodsEligible无癌症的妇女（年龄18-42，月经周期规律）谁曾在2005年和2013年之间筛选BRCA 1/2突变的标志物完成了一份问卷，并进行了单次抽血。E2测定与放射免疫法，IGF-1测定与酶联免疫吸附试验。ResultsEight-six妇女参加（44载体和42非载体）在这项研究中。BRCA突变载体显着年轻比非载体（P= 0.0002）。BRCA突变携带者和非携带者之间经年龄校正的基础（月经周期第2-5天）血清E2水平无显著差异（30.4 vs. 24.7 pg/mL，p= 0.07）。BRCA突变携带者与非携带者相比，经年龄校正的血清IGF-1水平显著较低（89.7 vs. 112.6 ng/mL，p< 0.001）。BRCA基因突变的女性发生低血清IGF-1水平（IGF-1 ≤85 ng/mL）的风险是无BRCA基因突变的女性的10.7倍（95%CI 2.5，46.2）。在调整年龄和BMI后，BRCA突变携带者的基础E2和IGF-1水平之间呈显着负相关（p= 0.03）。结论无癌症BRCA突变携带者的IGF-1水平显着低于BRCA阴性对照，并且E2之间存在潜在关联无癌症BRCA突变携带者中的IGF-1。我们的发现可能会促使未来的研究评估E2和IGF-1在BRCA突变携带者中的作用。
PurposeMajor clinical characteristics ofBRCA1/2-related cancers include association with estrogen and metabolic consequences. We aimed to evaluate serum estradiol (E2) and insulin-like growth factor 1 (IGF-1) levels as a marker of insulin resistance inBRCA1/2mutation carriers and high-risk,BRCA-negative controls.MethodsEligible cancer-free women (age 18–42 with regular menstrual cycles) who had been screened forBRCA1/2 mutations between 2005 and 2013 completed a questionnaire and underwent a single blood draw. E2 was measured with radioimmunoassay, and IGF-1 was measured with enzyme-linked immunosorbent assay.ResultsEighty-six women participated (44 carriers and 42 non-carriers) in this study.BRCAmutation carriers were significantly younger than non-carriers (p= 0.0002). Age-adjusted basal (menstrual cycle days 2–5) serum E2 level was not significantly different betweenBRCAmutation carriers and non-carriers (30.4 vs. 24.7 pg/mL,p= 0.07).BRCAmutation carriers have significantly lower age-adjusted serum IGF-1 levels compared to non-carriers (89.7 vs. 112.6 ng/mL,p< 0.001). In women withBRCAmutations, the risk of having low serum IGF-1 level (IGF-1: ≤85 ng/mL) was 10.7 times as great as that of women without BRCA mutations (95 % CI 2.5, 46.2). There was a significant inverse association between basal E2 and IGF-1 levels inBRCAmutation carriers after adjusting age and BMI (p= 0.03).ConclusionsIGF-1 level is significantly lower in cancer-freeBRCAmutation carriers versusBRCA-negative controls, and there is a potential association between E2 and IGF-1 in cancer-freeBRCAmutation carriers. Our findings may instigate future studies evaluating the role of both E2 and IGF-1 inBRCAmutation carriers.