Changes in adiposity over the life course and gene expression in postmenopausal women.

Background: 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.

Methods: 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.

Results: 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).

Conclusion: 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.