To identify reproductive, lifestyle, hormonal, and other correlates of circulating antimüllerian hormone (AMH) concentrations in mostly late premenopausal women.
Cross-sectional study.
Not ...applicable.
A total of 671 premenopausal women not known to have cancer.
None.
Concentrations of AMH were measured in a single laboratory using the picoAMH ELISA. Multivariable-adjusted median (and interquartile range) AMH concentrations were calculated using quantile regression for several potential correlates.
Older women had significantly lower AMH concentrations (≥40 n = 444 vs. <35 years n = 64, multivariable-adjusted median 0.73 ng/mL vs. 2.52 ng/mL). Concentrations of AMH were also significantly lower among women with earlier age at menarche (<12 n = 96 vs. ≥14 years n = 200: 0.90 ng/mL vs. 1.12 ng/mL) and among current users of oral contraceptives (n = 27) compared with never or former users (n = 468) (0.36 ng/mL vs. 1.15 ng/mL). Race, body mass index, education, height, smoking status, parity, and menstrual cycle phase were not significantly associated with AMH concentrations. There were no significant associations between AMH concentrations and androgen or sex hormone-binding globulin concentrations or with factors related to blood collection (e.g., sample type, time, season, and year of blood collection).
Among premenopausal women, lower AMH concentrations are associated with older age, a younger age at menarche, and currently using oral contraceptives, suggesting these factors are related to a lower number or decreased secretory activity of ovarian follicles.
Earlier age at onset of pubertal events and longer intervals between them (tempo) have been associated with increased breast cancer risk. It is unknown whether the timing and tempo of puberty are ...associated with adult breast density, which could mediate the increased risk.
From 1988 to 1997, girls participating in the Dietary Intervention Study in Children (DISC) were clinically assessed annually between ages 8 and 17 years for Tanner stages of breast development (thelarche) and pubic hair (pubarche), and onset of menses (menarche) was self-reported. In 2006-2008, 182 participants then aged 25-29 years had their percent dense breast volume (%DBV) measured by magnetic resonance imaging. Multivariable, linear mixed-effects regression models adjusted for reproductive factors, demographics, and body size were used to evaluate associations of age and tempo of puberty events with %DBV.
The mean (standard deviation) and range of %DBV were 27.6 (20.5) and 0.2-86.1. Age at thelarche was negatively associated with %DBV (p trend = 0.04), while pubertal tempo between thelarche and menarche was positively associated with %DBV (p trend = 0.007). %DBV was 40% higher in women whose thelarche-to-menarche tempo was 2.9 years or longer (geometric mean (95%CI) = 21.8% (18.2-26.2%)) compared to women whose thelarche-to-menarche tempo was less than 1.6 years (geometric mean (95%CI) = 15.6% (13.9-17.5%)).
Our results suggest that a slower pubertal tempo, i.e., greater number of months between thelarche and menarche, is associated with higher percent breast density in young women. Future research should examine whether breast density mediates the association between slower tempo and increased breast cancer risk.
Objective
Body mass index (BMI) does not directly measure adiposity, whereas dual‐energy x‐ray absorptiometry (DXA) provides valid direct estimates of adiposity. Therefore, this study evaluated ...usefulness of BMI as a measure of adiposity in serum metabolomics studies.
Methods
A cross‐sectional analysis was conducted of 202 women aged 25 to 29 years in the Dietary Intervention Study in Children Follow‐Up Study. Heights and weights were measured, and body composition was quantified using clinical DXA protocols. Serum metabolomic profiling was performed by liquid chromatography–tandem mass spectrometry. Partial correlations of BMI, percentage fat (%FAT), and total fat (TOTFAT) with log transformed serum metabolites were calculated.
Results
There was significant overlap in the 93 metabolites that correlated with BMI, %FAT, and/or TOTFAT; 9 differently correlated with BMI and %FAT, whereas 15 differently correlated with BMI and TOTFAT. Even for these metabolites, absolute differences were modest. Metabolite set enrichment analysis identified diacylglycerol and sphingolipid metabolism as overrepresented among metabolites significantly correlated with all three measures of adiposity.
Conclusions
BMI can be a good proxy for DXA measured %FAT and TOTFAT in descriptive metabolomic studies of healthy, young White women. Larger studies in more diverse populations are needed to endorse more generalized conclusions.
Background
Solid organ transplant recipients have an elevated risk of cancer. Quantifying the life‐years lost (LYL) due to cancer provides a complementary view of the burden of cancer distinct from ...other metrics and may identify subgroups of transplant recipients who are most affected.
Methods
Linked transplant and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987‐2014). Data on LYL due to cancer within 10 years posttransplant were derived using mean survival estimates from Cox models.
Results
Among 221,962 transplant recipients, 13,074 (5.9%) developed cancer within 10 years of transplantation. During this period, the mean LYL due to cancer were 0.16 years per transplant recipient and 2.7 years per cancer case. Cancer was responsible for a loss of 1.9% of the total life‐years expected in the absence of cancer in this population. Lung recipients had the highest proportion of total LYL due to cancer (0.45%) followed by heart recipients (0.29%). LYL due to cancer increased with age, from 0.5% among those aged birth to 34 years at transplant to 3.2% among those aged 50 years and older. Among recipients overall, lung cancer was the largest contributor, accounting for 24% of all LYL due to cancer, and non‐Hodgkin lymphoma had the next highest contribution (15%).
Conclusions
Transplant recipients have a shortened lifespan after developing cancer. Lung cancer and non‐Hodgkin lymphoma contribute strongly to LYL due to cancer within the first 10 years after transplant, highlighting opportunities to reduce cancer mortality through prevention and screening.
Transplantation recipients have a shortened lifespan after developing cancer. Lung cancer and non‐Hodgkin lymphoma contribute strongly to life‐years lost due to cancer, highlighting opportunities to reduce cancer mortality in this population through prevention and screening.
Purpose
Carbohydrate intake increases postprandial insulin secretion and may affect breast density, a strong risk factor for breast cancer, early in life. We examined associations of adolescent and ...early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars with breast density among 182 young women.
Methods
Diet was assessed using three 24-h recalls at each of five Dietary Intervention Study in Children (DISC) clinic visits when participants were age 10–19 years and at the DISC06 Follow-Up Study clinic visit when participants were age 25–29 years. Associations between energy-adjusted carbohydrates and MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at 25–29 years were quantified using multivariable-adjusted mixed-effects linear models.
Results
Adolescent sucrose intakes and premenarcheal total carbohydrates intakes were modestly associated with higher %DBV (mean %DBV
Q1 vs Q4
, 16.6 vs 23.5% for sucrose; and 17.2 vs 22.3% for premenarcheal total carbohydrates, all
P
trend
≤ 0.02), but not with ADBV. However, adolescent intakes of fiber and fructose were not associated with %DBV and ADBV. Early adulthood intakes of total carbohydrates, glycemic index/load, fiber, and simple sugars were not associated with %DBV and ADBV.
Conclusions
Insulinemic carbohydrate diet during puberty may be associated with adulthood breast density, but our findings need replication in larger studies.
Clinical Trials Registration
ClinicalTrials.gov Identifier, NCT00458588 April 9, 2007; NCT00000459 October 27, 1999
A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this ...association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.
What's new?
To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti‐Muellerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case‐control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.
Purpose
Alcohol consumption is an established breast cancer risk factor, though further research is needed to advance our understanding of the mechanism underlying the association. We used global ...metabolomics profiling to identify serum metabolites and metabolic pathways that could potentially mediate the alcohol–breast cancer association.
Methods
A cross-sectional analysis of reported alcohol consumption and serum metabolite concentrations was conducted among 211 healthy women 25–29 years old who participated in the Dietary Intervention Study in Children 2006 Follow-Up Study (DISC06). Alcohol–metabolite associations were evaluated using multivariable linear mixed-effects regression.
Results
Alcohol was significantly (FDR
p
< 0.05) associated with several serum metabolites after adjustment for diet composition and other potential confounders. The amino acid sarcosine, the omega-3 fatty acid eicosapentaenoate, and the steroid 4-androsten-3beta,17beta-diol monosulfate were positively associated with alcohol intake, while the gamma-tocopherol metabolite gamma-carboxyethyl hydroxychroman (CEHC) was inversely associated. Positive associations of alcohol with 2-methylcitrate and 4-androsten-3beta,17beta-diol disulfate were borderline significant (FDR
p
< 0.10). Metabolite set enrichment analysis identified steroids and the glycine pathway as having more members associated with alcohol consumption than expected by chance.
Conclusions
Most of the metabolites associated with alcohol in the current analysis participate in pathways hypothesized to mediate the alcohol–breast cancer association including hormonal, one-carbon metabolism, and oxidative stress pathways, but they could also affect risk via alternative pathways. Independent replication of alcohol–metabolite associations and prospective evaluation of confirmed associations with breast cancer risk are needed.
We previously reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.
This study assessed whether ...risk factors for breast cancer are correlates of AMH concentration.
This cross-sectional study included 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49) from 10 cohort studies among the general population.
Adjusting for age and cohort, AMH positively associated with age at menarche (P < 0.0001) and parity (P = 0.0008) and inversely associated with hysterectomy/partial oophorectomy (P = 0.0008). Compared with women of normal weight, AMH was lower (relative geometric mean difference 27%, P < 0.0001) among women who were obese. Current oral contraceptive (OC) use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, P < 0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, P = 0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40 vs ≥40), associations of AMH with body mass index and OCs were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (P-interaction < 0.05).
This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and it suggests that most associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
Breast cancer is frequently a hormonally dependent cancer, and associations of circulating estrogens and androgens with subsequent breast cancer risk are well established in postmenopausal women. ...Associations of serum estrogens and androgens with breast cancer risk in premenopausal women are less well studied. The objective of this study was to determine whether estradiol and testosterone levels in serum collected before menopause are associated with subsequent breast cancer risk.
We conducted a prospective case-control study of 266 participants who were registered in the Columbia, Missouri, Serum Bank and not using exogenous hormones at the time of blood collection. Each of 98 in situ or invasive breast cancer cases with prediagnostic serum collected before menopause was matched to two controls by age, date, menstrual cycle day, and time of day of blood collection. Estradiol and testosterone concentrations were quantified by using specific radioimmunoassays, and sex hormone-binding globulin (SHBG) was quantified with a chemiluminescent immunoassay to allow calculation of the non-SHBG bound hormone fractions. Data were analyzed by using conditional logistic regression. All tests of statistical significance were two-sided.
Serum testosterone was strongly and significantly associated with breast cancer risk. The relative odds (OR) for increasing quartiles of total testosterone were 1.0, 2.1 (95% confidence interval (CI) 0.9 to 4.8), 1.5 (95% CI, 0.6 to 3.4), and 3.3 (95% CI, 1.5 to 7.5, P(trend) = 0.006). Comparable ORs for the non-SHBG bound fraction of testosterone that is bioavailable were 1.0, 1.7 (95% CI, 0.7 to 4.2), 1.7 (95% CI, 0.7 to 4.0), and 4.2 (95% CI, 1.6 to 10.9, P(trend) = 0.002). Total and non-SHBG-bound estradiol were not associated with breast cancer, but extreme variation in levels across the menstrual cycle coupled with relatively small numbers, particularly for analyses stratified by cycle phase, limited the power to detect associations.
Results suggest that premenopausal women with elevated serum testosterone levels are at an increased risk of breast cancer.
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