Authors' Affiliations: Obstetrics & Gynaecology and Pediatrics, Dalhousie University, Halifax, Nova Scotia; Faculty of Physical Education and Recreation, University of Alberta; Cross Cancer Institute, Alberta Cancer Board, Edmonton; Alberta Health Services, Calgary, Alberta; Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute; Sunnybrook Research Institute, Toronto, Ontario; Department of Statistics, University of British Columbia, Vancouver; Southern Medical Program, University of British Columbia (Okanagan Campus), Kelowna, British Columbia, Canada; Fred Hutchison Cancer Research Center, Seattle, Washington; Keck School of Medicine, University of Southern California, Los Angeles, California; and Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico.
Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):2116-20. doi: 10.1158/1055-9965.EPI-13-0401. Epub 2013 Sep 9.
A relation between the breast cancer risk factors, insulin-like growth factor-I (IGF-I) and mammographic density, is biologically plausible, but results from cross-sectional epidemiologic studies have been mixed. Our objective was to examine the relation in a longitudinal manner, that is, between the change in circulating IGF-I concentrations and the change in mammographic measures over one year. Data from an exercise intervention trial conducted in 302 postmenopausal women ages 50 to 74 years were used. Blood drawn at baseline and postintervention was assessed for IGF-I and its binding protein (IGFBP-3) by direct chemiluminscent immunoassay. Area and volumetric measurements of mammographic dense fibroglandular and nondense fatty tissue were made. Statistical analyses were based on multiple linear regression. A one SD (20.2 ng/mL) change in IGF-I over one year was associated with small changes in percent dense area [mean: 0.8%; 95% confidence interval (CI), 0.1-1.4] and dense area (mean: 1.2 cm(2); 95% CI, 0.2-2.1). Change in IGFBP-3 was also associated with percent and absolute dense area. Absolute and percent dense volume, and mammographic measures representing fatty tissue (nondense area and volume) were not associated with changes in IGF-I and IGFBP-3. Longitudinal associations may be more detectable than cross-sectional associations due to the absence of confounding by invariant personal factors. Absolute and percent dense area, measures that are related to breast cancer risk, may be affected by IGF-I. Confirmation should be sought in further longitudinal studies in which larger changes in the IGF system are evoked.
乳腺癌风险因素、胰岛素样生长因子-I(IGF-I)和乳腺 X 线密度之间的关系在生物学上是合理的,但来自横断面流行病学研究的结果却存在差异。我们的目的是通过纵向方式(即在一年内循环 IGF-I 浓度的变化与乳腺 X 线密度的变化之间)来检查这种关系。本研究使用了一项在 302 名年龄在 50 至 74 岁之间的绝经后妇女中进行的运动干预试验的数据。基线和干预后采集的血液通过直接化学发光免疫测定法评估 IGF-I 和其结合蛋白(IGFBP-3)。对乳腺 X 线片致密纤维腺体和非致密脂肪组织的面积和体积进行测量。统计分析基于多元线性回归。IGF-I 在一年内的一个标准差(20.2ng/ml)变化与致密区域百分比的小变化相关[平均值:0.8%;95%置信区间(CI):0.1-1.4]和致密区域(平均值:1.2cm2;95%CI:0.2-2.1)。IGFBP-3 的变化也与百分比和绝对致密面积相关。绝对和百分比致密体积,以及代表脂肪组织的乳腺 X 线测量值(非致密面积和体积)与 IGF-I 和 IGFBP-3 的变化无关。由于不存在不变的个体因素的混杂,纵向关联可能比横断面关联更易被检测到。绝对和百分比致密面积,与乳腺癌风险相关的测量值,可能受 IGF-I 的影响。在进一步的纵向研究中,应该寻求更大的 IGF 系统变化来证实这一结果。