Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine, Saint Louis, Missouri, USA.
Alvin J. Siteman Cancer Center, Barnes-Jewish Hospital and Washington University School of Medicine, Saint Louis, Missouri, USA.
Cancer Med. 2022 Jul;11(13):2699-2710. doi: 10.1002/cam4.4649. Epub 2022 Mar 19.
Early life adiposity and changes in adiposity over the life course are associated with mammographic breast density among postmenopausal women. However, the underlying mechanisms are unknown; therefore, we comprehensively examined the associations of early life body mass index (BMI) and changes in BMI from ages 10, 18 to age at mammogram with growth factor, RANK pathway, and sex hormone gene expression in 372 postmenopausal women.
We estimated early life BMI at age 10 using the validated 9-level Stunkard pictogram. We calculated BMI at other ages (18, 30, and current age at mammogram) by dividing weight in kilograms at these ages with height in meters squared. Sequencing for gene expression was performed using the NanoString nCounter system. After adjusting for confounders, we estimated associations using multivariable linear regressions.
A 10 kg/m increase in early life BMI at age 10 was associated with a 17.2% decrease in RANKL gene expression (95% confidence interval [CI] = -30.8, -0.9) but was not associated with changes in other markers. BMI changes from ages 10, 18 to age at mammogram were associated with an increase in BMP2 and decreases in RANK, RANKL, and TNFRSF13B gene expression but were not associated with gene expression of other markers. A 10 kg/m increase in early life BMI from age 10 to current age was associated with a 7.8% increase in BMP2 (95% CI = -1.4, 17.8), an 8.5% decrease in RANK (95% CI = -13.9, -2.8), a 10.4% decrease in RANKL (95% CI = -16.9, -3.3), and an 8.5% decrease in TNFRSF13B gene expression (95% CI = -13.8, -2.8).
The results provide new insights into the biological mechanisms underlying the associations of adiposity changes from early life to adulthood and early life adiposity with mammographic breast density in postmenopausal women.
生命早期肥胖和生命过程中肥胖的变化与绝经后妇女的乳房 X 光密度有关。然而，其潜在机制尚不清楚；因此，我们全面检查了生命早期 BMI（体重指数）和从 10 岁、18 岁到乳房 X 光检查时 BMI 的变化与 372 名绝经后妇女的生长因子、RANK 通路和性激素基因表达之间的关系。
我们使用经过验证的 9 级 Stunkard 示意图来估计生命早期 10 岁时的 BMI。我们通过将这些年龄时的体重（公斤）除以身高（米的平方）来计算其他年龄（18 岁、30 岁和当前的乳房 X 光检查时的年龄）的 BMI。使用 NanoString nCounter 系统进行基因表达测序。在调整混杂因素后，我们使用多变量线性回归来估计关联。
生命早期 10 岁时 BMI 每增加 10kg/m，RANKL 基因表达降低 17.2%（95%置信区间 [CI] = -30.8，-0.9），但与其他标志物的变化无关。从 10 岁、18 岁到乳房 X 光检查时的 BMI 变化与 BMP2 增加和 RANK、RANKL 和 TNFRSF13B 基因表达降低有关，但与其他标志物的基因表达无关。生命早期 10 岁至当前 BMI 每增加 10kg/m，BMP2 增加 7.8%（95% CI = -1.4，17.8），RANK 减少 8.5%（95% CI = -13.9，-2.8），RANKL 减少 10.4%（95% CI = -16.9，-3.3），TNFRSF13B 基因表达减少 8.5%（95% CI = -13.8，-2.8）。
研究结果为生命早期到成年期肥胖变化和生命早期肥胖与绝经后妇女乳房 X 光密度之间关联的潜在机制提供了新的见解。
