Abstract PS7-03: Changes in body mass index (BMI) over the life course are associated with gene expression in postmenopausal women

Abstract

Abstract Introduction: Changes in body mass index (BMI) over the life course are associated with both mammographic breast density and breast cancer risk in postmenopausal women. The underlying biological mechanisms driving these associations are, however, yet to be elucidated. Understanding these mechanisms could provide important insights into breast cancer prevention early in life. To provide insight into the biological mechanisms underlying the associations of BMI change over the life course and breast cancer risk in postmenopausal women, we comprehensively investigated the associations of BMI change from ages 10 and 18 to current age with gene expression of biomarkers that have previously been associated with breast cancer risk: growth factors (IGF1, IGFBP3, FGF1, FGF12, TGFB1), sex hormones (PRL, PGR, ESR1, STAT1, STAT5), and receptor activator of nuclear factor-κB (RANK) pathway (RANK, RANKL, OPG, BMP2, TNFRSF13B, TNFRSF18) gene expression in postmenopausal women. Methods: We investigated these in 372 postmenopausal women free from breast cancer recruited during annual screening mammogram. We estimated BMI at age 10 using a validated 9-level pictogram. Gene expression levels were measured using NanoString nCounter system. We investigated the associations of BMI change with gene expression in multivariable linear regression models, adjusted for confounders. Results: The mean age of study participants was 58 years. Increase in BMI over the life course was associated with an increase in BMP2 gene expression but a decrease in RANK, RANKL, and TNFRSF13B gene expression. Compared to women who had a BMI gain of 0.1-5 kg/m2 from age 10, BMP2 gene expression increased in women who had a BMI gain of 5.1-10 kg/m2 (beta coefficient [β] = 0.48, 95% confidence interval [95% CI] = 0.04 to 0.92); BMI gain of 10.1-15 kg/m2 (β = 0.47, 95% CI = 0.03 to 0.91); and BMI gain of > 15 kg/m2 (β = 0.58, 95% CI = 0.15 to 1.02) (p-trend = 0.04). Similar results were observed for BMI gains from age 18 (p-trend < 0.01). Compared to women who had a BMI gain of 0.1-5 kg/m2 from age 10, RANK gene expression decreased in women who had a BMI gain of 5.1-10 kg/m2 (β = -0.21, 95% CI= -0.51 to 0.09); BMI gain of 10.1-15 kg/m2 (β = -0.29, 95% CI= -0.59 to 0.00); and BMI gain of >15 kg/m2 (β = -0.37, 95% CI= -0.66 to -0.07) (p-trend < 0.01). Similar results were observed for weight gains from age 10 and RANKL and TNFRSF13B gene expression, although the associations were weaker for RANKL gene expression. Changes in BMI over the life course were not associated with OPG, growth factors or sex hormone gene expression. Conclusions: Changes in BMI from childhood, late adolescence, and early adulthood were associated with RANK pathway gene expression in postmenopausal women. Our findings offer important and innovative new insights into how childhood adiposity may confer long-term protection against breast cancer risk in postmenopausal women. Citation Format: Yunan Han, Graham A Colditz, Adetunji T Toriola. Changes in body mass index (BMI) over the life course are associated with gene expression in postmenopausal women [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-03.