Department of Epidemiology, Fielding School of Public Health, University of California, 650 Charles Young Drive South, Room 71-264 CHS, Los Angeles, CA, 90095, USA.
Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg im Breisgau, Germany.
Breast Cancer Res. 2020 Oct 1;22(1):104. doi: 10.1186/s13058-020-01338-y.
Systemic inflammation may play a role in shaping breast composition, one of the strongest risk factors for breast cancer. Pubertal development presents a critical window of breast tissue susceptibility to exogenous and endogenous factors, including pro-inflammatory markers. However, little is known about the role of systemic inflammation on adolescent breast composition and pubertal development among girls.
We investigated associations between circulating levels of inflammatory markers (e.g., interleukin-6 (IL-6), tumor necrosis factor receptor 2 (TNFR2), and C-reactive protein (CRP)) at Tanner stages 2 and 4 and breast composition at Tanner stage 4 in a cohort of 397 adolescent girls in Santiago, Chile (Growth and Obesity Cohort Study, 2006-2018). Multivariable linear models were used to examine the association between breast composition and each inflammatory marker, stratifying by Tanner stage at inflammatory marker measurement. Accelerated failure time models were used to evaluate the association between inflammatory markers concentrations at each Tanner stage and time to menarche.
In age-adjusted linear regression models, a doubling of TNFR2 at Tanner 2 was associated with a 26% (95% CI 7-48%) increase in total breast volume at Tanner 4 and a 22% (95% CI 10-32%) decrease of fibroglandular volume at Tanner 4. In multivariable models further adjusted for body fatness and other covariates, these associations were attenuated to the null. The time to menarche was 3% (95% CI 1-5%) shorter among those in the highest quartile of IL-6 at Tanner 2 relative to those in the lowest quartile in fully adjusted models. Compared to those in the lowest quartile of CRP at Tanner 4, those in the highest quartile experienced 2% (95% CI 0-3%) longer time to menarche in multivariable models.
Systemic inflammation during puberty was not associated with breast volume or breast density at the conclusion of breast development among pubertal girls after adjusting for body fatness; however, these circulating inflammation biomarkers, specifically CRP and IL-6, may affect the timing of menarche onset.
系统性炎症可能在塑造乳房组成方面发挥作用，而乳房组成是乳腺癌最强的风险因素之一。青春期是乳房组织对外源性和内源性因素（包括促炎标志物）易感性的关键时期。然而，人们对青春期系统性炎症与女孩乳房组成和青春期发育之间的关系知之甚少。
我们在智利圣地亚哥的一个青少年女孩队列（生长和肥胖队列研究，2006-2018 年）中研究了在 Tanner 2 期和 4 期时循环炎症标志物（如白细胞介素 6（IL-6）、肿瘤坏死因子受体 2（TNFR2）和 C 反应蛋白（CRP））水平与 Tanner 4 期时乳房组成之间的关联。使用多变量线性模型，按炎症标志物测量时的 Tanner 分期对乳房组成与每种炎症标志物之间的关联进行分层。使用加速失效时间模型评估每个 Tanner 分期时炎症标志物浓度与初潮时间之间的关联。
在年龄调整的线性回归模型中，Tanner 2 期时 TNFR2 增加一倍，与 Tanner 4 期时总乳房体积增加 26%（95%CI7-48%）和乳房密度减少 22%（95%CI10-32%）相关。在进一步调整体脂肪和其他协变量的多变量模型中，这些关联趋于零。在完全调整模型中，与 Tanner 2 期时处于 IL-6 最低四分位数的人相比，处于最高四分位数的人初潮时间提前 3%（95%CI1-5%）。与 Tanner 4 期时 CRP 最低四分位数的人相比，最高四分位数的人初潮时间延迟 2%（95%CI0-3%）。
在调整体脂肪后，青春期系统性炎症与青春期女孩发育结束时的乳房体积或乳房密度无关；然而，这些循环炎症生物标志物，特别是 CRP 和 IL-6，可能会影响初潮的时间。
