[Show abstract][Hide abstract] ABSTRACT: Overweight and obesity in childhood and adolescence are associated with reduced breast cancer risk, independent of adult body mass index (BMI). These associations may be mediated through breast density.
We prospectively examined associations of early life body fatness with adult breast density measured by MRI in 182 women in the Dietary Intervention Study in Children (DISC) who were ages 25-29 at follow-up. Height, weight, and other factors were measured at baseline (ages 8-10) and annual clinic visits through adolescence. We used linear mixed-effects models to quantify associations of percent breast density and dense and non-dense breast volume at ages 25-29 with quartiles of age-specific youth body mass index (BMI) Z-scores, adjusting for clinic, treatment group, current adult BMI, and other well-established risk factors for breast cancer and predictors of breast density.
We observed inverse associations between age-specific BMI Z-scores at all youth clinic visits and percent breast density, adjusting for current adult BMI and other covariates (all p values <0.01). Women whose baseline BMI Z-scores (at ages 8-10 years) were in the top quartile had significantly lower adult breast density, after adjusting for current adult BMI and other covariates [least squares mean (LSM): 23.4 %; 95 % confidence interval (CI): 18.0 %, 28.8 %] compared to those in the bottom quartile (LSM: 31.8 %; 95 % CI: 25.2 %, 38.4 %) (p trend <0.01). Significant inverse associations were also observed for absolute dense breast volume (all p values <0.01), whereas there were no clear associations with non-dense breast volume.
These results support the hypothesis that body fatness during childhood and adolescence may play an important role in premenopausal breast density, independent of current BMI, and further suggest direct or indirect influences on absolute dense breast volume.
NCT00458588 ; April 9, 2007.
Breast cancer research: BCR 12/2015; 17(1):95. DOI:10.1186/s13058-015-0601-4 · 5.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Obesity and its consequences, such as diabetes, are global health issues that burden about 171 × 10(6) adult individuals worldwide. Fat mass index (FMI, kg/m(2)), fat-free mass index (FFMI, kg/m(2)), and percent fat mass may be useful to evaluate under- and overnutrition and muscle development in a clinical or research environment. This proof-of-concept study tested whether frontal whole-body silhouettes could be used to accurately measure body composition parameters using active shape modeling (ASM) techniques.
Binary shape images (silhouettes) were generated from the skin outline of dual-energy x-ray absorptiometry (DXA) whole-body scans of 200 healthy children of ages from 6 to 16 yr. The silhouette shape variation from the average was described using an ASM, which computed principal components for unique modes of shape. Predictive models were derived from the modes for FMI, FFMI, and percent fat using stepwise linear regression. The models were compared to simple models using demographics alone [age, sex, height, weight, and body mass index z-scores (BMIZ)].
The authors found that 95% of the shape variation of the sampled population could be explained using 26 modes. In most cases, the body composition variables could be predicted similarly between demographics-only and shape-only models. However, the combination of shape with demographics improved all estimates of boys and girls compared to the demographics-only model. The best prediction models for FMI, FFMI, and percent fat agreed with the actual measures with R(2) adj. (the coefficient of determination adjusted for the number of parameters used in the model equation) values of 0.86, 0.95, and 0.75 for boys and 0.90, 0.89, and 0.69 for girls, respectively.
Whole-body silhouettes in children may be useful to derive estimates of body composition including FMI, FFMI, and percent fat. These results support the feasibility of measuring body composition variables from simple cameras such as those found in cell phones.
Medical Physics 08/2015; 42(8):4668. DOI:10.1118/1.4926557 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: INTRODUCTION: During adolescence the breasts undergo rapid growth and development under the influence of sex hormones. Although the hormonal etiology of breast cancer is hypothesized, it remains unknown whether adolescent sex hormones are associated with adult breast density, which is a strong risk factor for breast cancer.
METHODS: Percentage of dense breast volume (%DBV) was measured in 2006 by magnetic resonance imaging in 177 women aged 25–29 years who had participated in the Dietary Intervention Study in Children from 1988 to 1997. They had sex hormones and sex hormone-binding globulin (SHBG) measured in serum collected on one to five occasions between 8 and 17 years of age. Multivariable linear mixed-effect regression models were used to evaluate the associations of adolescent sex hormones and SHBG with %DBV.
RESULTS: Dehydroepiandrosterone sulfate (DHEAS) and SHBG measured in premenarche serum samples were significantly positively associated with %DBV (all Ptrend ≤0.03) but not when measured in postmenarche samples (all Ptrend ≥0.42). The multivariable geometric mean of %DBV across quartiles of premenarcheal DHEAS and SHBG increased from 16.7 to 22.1 % and from 14.1 to 24.3 %, respectively. Estrogens, progesterone, androstenedione, and testosterone in pre- or postmenarche serum samples were not associated with %DBV (all Ptrend ≥0.16).
CONCLUSIONS: Our results suggest that higher premenarcheal DHEAS and SHBG levels are associated with higher %DBV in young women. Whether this association translates into an increased risk of breast cancer later in life is currently unknown.
Breast Cancer Research 06/2015; 17(1):77. DOI:10.1186/s13058-015-0581-4 · 5.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We aimed to determine if adult bone mineral density (BMD) susceptibility loci were associated with pediatric bone mass and density, and if sex and pubertal stage influenced any association. We analyzed prospective areal BMD (aBMD) and bone mineral content (BMC) data from the Bone Mineral Density in Childhood Study (N = 603, European ancestry, 54% female). Linear mixed models were used to assess if 77 single nucleotide polymorphisms (SNPs) near known adult BMD susceptibility loci interacted with sex and pubertal stage to influence the aBMD/BMC; adjusting for age, BMI, physical activity, and dietary calcium. The strongest main association was observed between a SNP near C7orf58 and distal radius aBMD. However, this association had a significant sex•SNP interaction, revealing a significant association only in females (b = -0.32, P = 1.8 × 10(-6) ). Furthermore, the C12orf23 locus had significant interactions with both sex and pubertal stage, revealing associations in females during Tanner stage I for total hip aBMD (b = 0.24, P = 0.001) and femoral neck aBMD (b = 0.27, P = 3.0 × 10(-5) ). In contrast, the sex•SNP interactions for loci near LRP5 and WNT16 uncovered associations that were only in males for total body less head BMC (b = 0.22, P = 4.4 × 10(-4) ) and distal radius aBMD (b = 0.27, P = 0.001), respectively. Furthermore, the LRP5 locus interacted with both sex and pubertal stage, demonstrating associations that were exclusively in males during Tanner V for total hip aBMD (b = 0.29, P = 0.003). In total, significant sex•SNP interactions were found at 15 loci; pubertal stage•SNP interactions at 23 loci and 19 loci interacted with both sex and pubertal stage. In conclusion, variants originally associated with adult BMD influence bone mass in children of European ancestry, highlighting the fact that many of these loci operate early in life. However, the direction and magnitude of associations for a large number of SNPs only became evident when accounting for sex and maturation. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research 03/2015; 30(9). DOI:10.1002/jbmr.2508 · 6.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Elevated mammographic density is a breast cancer risk factor, which has a suggestive, but unproven, relationship with increased exposure to sex steroid hormones. We examined associations of serum estrogens and estrogen metabolites with area and novel volume mammographic density measures among 187 women, ages 40–65, undergoing diagnostic breast biopsies at an academic facility in Vermont. Serum parent estrogens, estrone and estradiol, and their 2-, 4-, and 16-hydroxylated metabolites were measured using liquid chromatography-tandem mass spectrometry. Area mammographic density was measured in the breast contralateral to the biopsy using thresholding software; volume mammographic density was quantified using a density phantom. Linear regression was used to estimate associations of estrogens with mammographic densities, adjusted for age and body mass index, and stratified by menopausal status and menstrual cycle phase. Weak, positive associations between estrogens, estrogen metabolites, and mammographic density were observed, primarily among postmenopausal women. Among premenopausal luteal phase women, the 16-pathway metabolite estriol was associated with percent area (p = 0.04) and volume (p = 0.05) mammographic densities and absolute area (p = 0.02) and volume (p = 0.05) densities. Among postmenopausal women, levels of total estrogens, the sum of parent estrogens, and 2-, 4- and 16-hydroxylation pathway metabolites were positively associated with area density measures (percent: p = 0.03, p = 0.04, p = 0.01, p = 0.02, p = 0.07; absolute: p = 0.02, p = 0.02, p = 0.01, p = 0.02, p = 0.03, respectively) but not volume density measures. Our data suggest that serum estrogen profiles are weak determinants of mammographic density and that analysis of different density metrics may provide complementary information about relationships of estrogen exposure to breast tissue composition.