The objective of this study is to examine the role of early lifetime exposure to physical activity on magnetic resonance imaging-determined breast density measures.
Associations of adolescent (high ...school (ages 14-17 yr) and early adulthood, post-high school (ages 18-21 yr) and past year) leisure-time physical activity, as well as a principal component score including all three estimates, were examined with percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) in a cross-sectional analysis of 182 healthy women, ages 25-29 yr, enrolled in the Dietary Intervention Study in Children Follow-up Study (DISC06). Generalized linear mixed models were used to examine associations after adjustment for relevant covariates for the entire analytic sample. Analyses were repeated in nulliparous women and hormonal contraceptive nonusers.
Physical activity during high school and post-high school were not statistically significantly related to %DBV or ADBV in multivariable models. Past year physical activity was positively related to %DBV in the unadjusted and partially adjusted models (P < 0.001 and P = 0.01, respectively), which did not adjust for body mass index (BMI). After additional adjustment for childhood and early adulthood BMI, this association became nonstatistically significant. The relation between past year physical activity and ADBV was not statistically significant. These findings were similar in nonusers of hormonal contraceptives. No statistically significant relations were found in nulliparous women or between the principal component score and %DBV or ADBV.
Results from this study are consistent with previous research suggesting that physical activity during adolescence and early adulthood is unrelated to breast density.
Elevated circulating levels of the adrenal androgen dehydroepiandrosterone (DHEA) and its sulfate (DHEAS) are associated with increased breast cancer risk in prospective studies. Genetic variants in ...hypothalamic-pituitary-adrenal (HPA) axis genes may contribute to these circulating hormone levels, and consequently to breast cancer risk. No previous studies have examined the effects of genetic variants in HPA axis genes on breast cancer risk. We evaluated the associations of 49 single nucleotide polymorphisms (SNPs) in five HPA axis genes (NR3C1, NR3C2, CRH, CRHR1, and CRHBP) with the risk of breast cancer in the Women's Insights and Shared Experiences (WISE) Study of Caucasians (346 cases and 442 controls), as well as African Americans (149 cases and 246 controls). Of the 49 SNPs evaluated, one showed a nominal significant association (P for trend < 0.05) with breast cancer risk among Caucasians, and another two among African Americans. The age-adjusted additive odds ratio (OR) (95% confidence interval (95% CI)) of the SNP rs11747190A in the CRHBP gene for the risk of breast cancer among Caucasian women was 1.45 (1.09-1.94). The age-adjusted additive ORs (95% CIs) of two SNPs (CRHBP rs1700688T and CRHR1 rs17689471C) for the risk of breast cancer among African American women were 1.84 (1.13-2.98) and 2.48 (1.20-5.13), respectively. However, these SNPs did not show significant associations after correction for multiple testing. Our findings do not provide strong supportive evidence for the contribution of genetic variants in these HPA axis genes to the risk of developing breast cancer in either Caucasians or African Americans.
Accumulating data suggest that depression is associated with risk factors for cardiovascular disease, but few studies have investigated potential behavioral mediators of such associations, ...particularly among women. In this study of healthy young adult women (n = 225), we examined associations among depressive symptoms, health behaviors, and serum lipid levels. Depressive symptoms were assessed with the 20-item Center for Epidemiologic Studies-Depression scale, and a fasting blood sample was obtained for serum lipid levels, including total cholesterol, high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C). Diet was measured using 24-h recalls, and other health behaviors (physical activity, smoking) were assessed via self-report questionnaire. Results indicated a modest negative association between depressive symptoms and LDL-C levels. Higher levels of depressive symptoms were also associated with lower total and insoluble dietary fiber intake, both of which were associated with HDL-C and LDL-C. Mediational analyses indicated a significant indirect effect of depressive symptoms on LDL-C via total and insoluble dietary fiber in unadjusted analyses, but not in adjusted analyses. The present findings suggest that depressive symptoms are inversely associated with serum LDL-C levels in young adult women, but that these associations are not likely mediated by adverse lifestyle behaviors.
Background Müllerian inhibiting substance (MIS) is a member of the transforming growth factor β family of growth and differentiation factors that inhibits elongation and branching of mammary ducts ...and has been shown to inhibit mammary tumor growth in vitro and in animal models. The objective of this study was to determine whether serum MIS levels are associated with breast cancer risk. Methods We conducted a prospective case–control study of 309 participants who were registered in the Columbia, Missouri Serum Bank. Each of 105 in situ or invasive breast cancer case patients with prediagnostic serum collected before menopause was matched to two control subjects by age, date, menstrual cycle day, and time of day of blood collection. MIS was measured in serum by using an enzyme-linked immunosorbent assay, and estradiol and testosterone concentrations were quantified by using specific radioimmunoassays. Data were analyzed using conditional logistic regression. All tests of statistical significance were two-sided. Results The relative odds ratio of breast cancer for women in increasing MIS quartiles were 1, 2.8 (95% confidence interval CI = 1.0 to 7.4), 5.9 (95% CI = 2.4 to 14.6), and 9.8 (95% CI = 3.3 to 28.9, Ptrend < .001). The association of MIS with breast cancer was weaker in women who were not taking oral contraceptives at the time of blood collection, but adjustment for estradiol and testosterone levels did not materially alter results for these women. The association of MIS with breast cancer did not vary by age at blood collection but was stronger among women who were diagnosed with breast cancer at an older age than among those who were diagnosed at a younger age. Conclusion MIS may be a novel biomarker of increased breast cancer risk. Additional research including confirmatory epidemiological studies and mechanistic studies is needed.
Abstract Purpose This study examined the associations of free testosterone and family environment with delinquent and aggressive behaviors among adolescent boys and girls with elevated low-density ...lipoprotein (LDL)–cholesterol levels. Methods Participants were 164 boys and 180 girls 11–14 years of age. The female parent provided ratings of family cohesion and of child aggressive and delinquent behaviors. Tanner ratings of pubertal development were obtained during physical examination, and a blood sample was drawn for assessment of serum levels of free testosterone. Results Hierarchical regression analyses revealed significant two-way interactions of free testosterone and family cohesion on delinquent behaviors among adolescent boys and girls. Specifically, under conditions of low family cohesion, free testosterone was positively associated with delinquent behaviors among boys, whereas in families with high cohesion no association between free testosterone and delinquent behavior was observed. In contrast, free testosterone was negatively associated with delinquent behaviors among adolescent girls in low-cohesion families. For girls, family cohesion was negatively associated with aggressive behaviors; for boys, LDL-C was positively associated with aggressive behaviors. Conclusions Child gender and family environment factors appear to modify the associations between free testosterone and delinquent behaviors in adolescent boys and girls.
Concern has been raised about the adequacy of radioimmunoassays to measure steroid sex hormones in population studies. We compared steroid sex hormone measurements in serum by radioimmunoassay with ...mass spectrometry. Four male and four female serum pools with known relative concentrations of steroid sex hormones were measured multiple times by both methods. Because measurements are expected to increase linearly with concentration for each sex, we examined whether the linear regressions of hormone measurements on concentration were the same for radioimmunoassay and mass spectrometry. Estradiol, estrone, androstenedione, testosterone, and dehydroepiandrosterone sulfate were measured in female pools; testosterone, dihydrotestosterone, androstenedione, and dehydroepiandrosterone sulfate were measured in male pools. Regression slopes for radioimmunoassay and mass spectrometry measurements were comparable for all hormones except androstenedione, which had a steeper slope when measured by mass spectrometry (
P ≤ 0.02). Intercepts for radioimmunoassay and mass spectrometry were similar and close to zero for estradiol, androstenedione, dehydroepiandrosterone sulfate, and in male samples, testosterone. For testosterone in female samples, estrone, and dihydrotestosterone, radioimmunoassay and mass spectrometry intercepts differed significantly. Standard deviations of individual measurements by radioimmunoassay and mass spectrometry differed by hormone and serum concentration; neither method consistently measured hormone concentrations with less variability. Our findings suggest that although absolute concentrations may differ for some hormones, radioimmunoassay and mass spectrometry can yield similar estimates of between subject differences in serum concentrations of most steroid sex hormones commonly measured in population studies. Relative power of studies using radioimmunoassay and mass spectrometry will depend on the hormones measured and their serum concentrations.
Background Birth characteristics and adult hormone concentrations influence breast cancer risk, but little is known about the influence of birth characteristics on hormone concentrations, ...particularly during adolescence. Methods We evaluated the association of birth characteristics (birth weight, birth length, and gestational age) with serum sex hormone concentrations during late childhood and adolescence in 278 female participants of the Dietary Intervention Study in Children. Repeated measures analysis of variance models were used to assess the relationships of birth characteristics and serum estrogens and androgens at five different time points over a mean period of 7 years. Results In analyses that did not take into account time from blood draw until menarche, birth weight was inversely associated with pre-menarche concentrations of estradiol, estrone sulfate, androstenedione, testosterone, and dehydroepiandrosterone sulfate (DHEAS). In the post-menarche analyses, birth weight was not significantly associated with concentration of any of the hormones under investigation. Birth length and gestational age were not associated with hormone concentrations before or after menarche. Conclusion Birth weight is inversely associated with sex hormone concentrations before menarche in the model unadjusted for time from blood draw until menarche. Impact The in utero environment has long-term influences on the hormonal milieu, which could potentially contribute to breast cancer risk.
Objective To examine whether birth weight, birth length, and gestational age are individually associated with age at menarche. Methods Analyses were conducted using data from n = 278 female ...participants in the Dietary Intervention Study in Children (DISC). Age at menarche was prospectively collected as part of the original DISC investigation. DISC participants self-reported birth weight, birth length, and gestational age with assistance from their mothers and other records as part of the DISC06 Follow-up Study at ages 25-29. Linear regression was used to estimate the association of birth characteristics and age at menarche. Results Birth weight was positively associated with age at menarche (p ≤ 0.01) in multiple regression analyses after controlling for BMI-for-age percentile, race and DISC treatment group. No statistically significant relationships were detected between either length or gestational age and age at menarche. Conclusions Higher birth weight may be associated with a modest delay in age at menarche.
Objective
The present study examined associations between psychological reactivity and hormonal responses to a standardized laboratory stressor (Trier Social Stress Test, TSST) in postmenopausal ...women.
Methods
Postmenopausal women aged 50–74 years undertook anxiety and mood assessments prior to and following the TSST. Blood samples were drawn at multiple timepoints for assessment of cortisol, adrenocorticotrophic hormone (ACTH) and dehydroepiandrosterone (DHEA).
Results
Forty postmenopausal women completed the assessments. As expected, significant increases in anxiety and negative affect and decreases in positive affect were observed after the TSST; however, the magnitude of change in anxiety and mood varied considerably across individuals. Analyses indicated that greater increases in anxiety and negative affect after the TSST were associated with higher levels of cortisol, ACTH and DHEA after controlling for race, age, body mass index and smoking status. Changes in positive affect were not associated with cortisol, ACTH or DHEA.
Conclusions
These findings suggest that enhanced reactivity to stress is associated with higher hormone levels among postmenopausal women, which could have potential implications for health.
Abstract Introduction : Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines ...have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods : Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results : Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = −0.26, p -value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin ( r = 0.38, p = 0.0013; r = −0.32, p = 0.0076), and increasing body mass index (BMI) ( r = −0.31, p = < 0.0001; r = 0.39, p = < 0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users ( p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 ( p = 0.78), or resistin ( p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI ( p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion : lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.
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