Carotenoids, micronutrients in fruits and vegetables, may reduce breast cancer risk. Most, but not all, past studies of circulating carotenoids and breast cancer have found an inverse association ...with at least one carotenoid, although the specific carotenoid has varied across studies.
We conducted a pooled analysis of eight cohort studies comprising more than 80% of the world's published prospective data on plasma or serum carotenoids and breast cancer, including 3055 case subjects and 3956 matched control subjects. To account for laboratory differences and examine population differences across studies, we recalibrated participant carotenoid levels to a common standard by reassaying 20 plasma or serum samples from each cohort together at the same laboratory. Using conditional logistic regression, adjusting for several breast cancer risk factors, we calculated relative risks (RRs) and 95% confidence intervals (CIs) using quintiles defined among the control subjects from all studies. All P values are two-sided.
Statistically significant inverse associations with breast cancer were observed for α-carotene (top vs bottom quintile RR = 0.87, 95% CI = 0.71 to 1.05, P(trend) = .04), β-carotene (RR = 0.83, 95% CI = 0.70 to 0.98, P(trend) = .02), lutein+zeaxanthin (RR = 0.84, 95% CI = 0.70 to 1.01, P(trend) = .05), lycopene (RR = 0.78, 95% CI = 0.62 to 0.99, P(trend) = .02), and total carotenoids (RR = 0.81, 95% CI = 0.68 to 0.96, P(trend) = .01). β-Cryptoxanthin was not statistically significantly associated with risk. Tests for heterogeneity across studies were not statistically significant. For several carotenoids, associations appeared stronger for estrogen receptor negative (ER(-)) than for ER(+) tumors (eg, β-carotene: ER(-): top vs bottom quintile RR = 0.52, 95% CI = 0.36 to 0.77, P(trend) = .001; ER(+): RR = 0.83, 95% CI = 0.66 to 1.04, P(trend) = .06; P(heterogeneity) = .01).
This comprehensive prospective analysis suggests women with higher circulating levels of α-carotene, β-carotene, lutein+zeaxanthin, lycopene, and total carotenoids may be at reduced risk of breast cancer.
Childhood adiposity is inversely associated with young adult percent dense breast volume (%DBV) and absolute dense breast volume (ADBV), which could contribute to its protective effect for breast ...cancer later in life. The objective of this study was to identify metabolites in childhood serum that may mediate the inverse association between childhood adiposity and young adult breast density.
Longitudinal data from 182 female participants in the Dietary Intervention Study in Children (DISC) and the DISC 2006 (DISC06) Follow-Up Study were analyzed. Childhood adiposity was assessed by anthropometry at the DISC visit with serum available that occurred closest to menarche and expressed as a body mass index (BMI) z-score. Serum metabolites were measured by untargeted metabolomics using ultra-high-performance liquid chromatography-tandem mass spectrometry. %DBV and ADBV were measured by magnetic resonance imaging at the DISC06 visit when participants were 25-29 years old. Robust mixed effects linear regression was used to identify serum metabolites associated with childhood BMI z-scores and breast density, and the R package mediation was used to quantify mediation.
Of the 115 metabolites associated with BMI z-scores (FDR < 0.20), 4 were significantly associated with %DBV and 6 with ADBV before, though not after, adjustment for multiple comparisons. Mediation analysis identified 2 unnamed metabolites, X-16576 and X-24588, as potential mediators of the inverse association between childhood adiposity and dense breast volume. X-16576 mediated 14% (95% confidence interval (CI) = 0.002, 0.46; P = 0.04) of the association of childhood adiposity with %DBV and 11% (95% CI = 0.01, 0.26; P = 0.02) of its association with ADBV. X-24588 also mediated 7% (95% CI = 0.001, 0.18; P = 0.05) of the association of childhood adiposity with ADBV. None of the other metabolites examined contributed to mediation of the childhood adiposity-%DBV association, though there was some support for contributions of lysine, valine and 7-methylguanine to mediation of the inverse association of childhood adiposity with ADBV.
Additional large longitudinal studies are needed to identify metabolites and other biomarkers that mediate the inverse association of childhood adiposity with breast density and possibly breast cancer risk.
Folate is the primary methyl donor and B vitamins are cofactors for one-carbon metabolism that maintain DNA integrity and epigenetic signatures implicated in carcinogenesis. Breast tissue is ...particularly susceptible to stimuli in early life. Only limited data are available on associations of one-carbon metabolism-related vitamin intake during youth and young adulthood with breast density, a strong risk factor for breast cancer.
Over 18 years in the DISC and DISC06 Follow-up Study, diets of 182 young women were assessed by three 24-hour recalls on five occasions at ages 8 to 18 years and once at 25 to 29 years. Multivariable-adjusted linear mixed-effects regression was used to examine associations of intakes of one-carbon metabolism-related vitamins with MRI-measured percent dense breast volume (%DBV) and absolute dense breast volume (ADBV) at ages 25 to 29 years.
Folate intake in youth was inversely associated with %DBV (Ptrend = 0.006) and ADBV (Ptrend = 0.02). These inverse associations were observed with intake during post-, though not premenarche. In contrast, premenarche vitamin B2 intake was positively associated with ADBV (Ptrend < 0.001). Young adult folate and vitamin B6 intakes were inversely associated with %DBV (all Ptrend ≤ 0.04), whereas vitamins B6 and B12 were inversely associated with ADBV (all Ptrend ≤ 0.04).
Among these DISC participants intakes of one-carbon metabolism-related vitamins were associated with breast density. Larger prospective studies among diverse populations are needed to replicate these findings.
Our results suggest the importance of one-carbon metabolism-related vitamin intakes early in life with development of breast density and thereby potentially breast cancer risk later in life.
Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone ...(AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.
In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.
The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.
AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
Background
Solid organ transplant recipients have an elevated risk of cancer. Quantifying deaths attributable to cancer can inform priorities to reduce cancer burden.
Methods
Linked transplantation ...and cancer registry data were used to identify incident cancers and deaths among solid organ transplant recipients in the United States (1987‐2014). Population‐attributable fractions (PAFs) of deaths due to cancer and corresponding cancer‐attributable mortality rates were estimated using Cox models.
Results
Among 221,962 solid organ transplant recipients, 15,012 developed cancer. Approximately 13% of deaths (PAF, 13.2%) were attributable to cancer, corresponding to a cancer‐attributable mortality rate of 516 per 100,000 person‐years. Lung cancer was the largest contributor to mortality (PAF, 3.1%), followed by non‐Hodgkin lymphoma (NHL; PAF, 1.9%), colorectal cancer (PAF, 0.7%), and kidney cancer (PAF, 0.5%). Cancer‐attributable mortality rates increased with age at transplantation, reaching 1229 per 100,000 person‐years among recipients aged ≥65 years. NHL was the largest contributor among children (PAF, 4.1%) and lung cancer was the largest contributor among recipients aged ≥50 years (PAFs, 3.7%‐4.3%). Heart recipients had the highest PAF (16.4%), but lung recipients had the highest cancer‐attributable mortality rate (1241 per 100,000 person‐years). Overall, mortality attributable to cancer increased steadily with longer time since transplantation, reaching 15.7% of deaths (810 per 100,000 person‐years) at ≥10 years after transplantation. Comparison of cancer‐attributable mortality rates with specified causes of death indicated that some deaths recorded as other causes might instead be caused by cancer or its treatment.
Conclusions
Cancer is a substantial cause of mortality among solid organ transplant recipients, with major contributions reported from lung cancer and NHL. Cancer‐attributable mortality increases with age and time since transplantation, and therefore cancer deaths will become an increasing burden as recipients live longer.
Cancer is a substantial cause of mortality among solid organ transplant recipients, with major contributions from lung cancer and non‐Hodgkin lymphoma. There are opportunities to reduce cancer mortality among these individuals through prevention and tailored screening.
Purpose of the study
Breast density is an established risk factor for breast cancer. However, little is known about metabolic influences on breast density phenotypes. We conducted untargeted serum ...metabolomics analyses to identify metabolic signatures associated with breast density phenotypes among young women.
Methods
In a cross-sectional study of 173 young women aged 25–29 who participated in the Dietary Intervention Study in Children 2006 Follow-up Study, 449 metabolites were measured in fasting serum samples using ultra-high-performance liquid chromatography-tandem mass spectrometry. Multivariable-adjusted mixed-effects linear regression identified metabolites associated with magnetic resonance imaging measured breast density phenotypes: percent dense breast volume (%DBV), absolute dense breast volume (ADBV), and absolute non-dense breast volume (ANDBV). Metabolite results were corrected for multiple comparisons using a false discovery rate adjusted p-value (q).
Results
The amino acids valine and leucine were significantly inversely associated with %DBV. For each 1 SD increase in valine and leucine, %DBV decreased by 20.9% (
q
= 0.02) and 18.4% (
q
= 0.04), respectively. ANDBV was significantly positively associated with 16 lipid and one amino acid metabolites, whereas no metabolites were associated with ADBV. Metabolite set enrichment analysis also revealed associations of distinct metabolic signatures with %DBV, ADBV, and ANDBV; branched chain amino acids had the strongest inverse association with %DBV (
p
= 0.002); whereas, diacylglycerols and phospholipids were positively associated with ANDBV (
p
≤ 0.002), no significant associations were observed for ADBV.
Conclusion
Our results suggest an inverse association of branched chain amino acids with %DBV. Larger studies in diverse populations are needed.
Endogenous estradiol and estrone are linked causally to increased risks of breast cancer. In this study, we evaluated multiple competing hypotheses for how metabolism of these parent estrogens may ...influence risk. Prediagnostic concentrations of estradiol, estrone, and 13 metabolites were measured in 1,298 postmenopausal cases of breast cancer and 1,524 matched controls in four separate patient cohorts. The median time between sample collection and diagnosis was 4.4 to 12.7 years across the cohorts. Estrogen analytes were measured in serum or urine by liquid chromatography-tandem mass spectrometry. Total estrogen levels (summing all 15 estrogens/estrogen metabolites) were associated strongly and positively with breast cancer risk. Normalizing total estrogen levels, we also found that a relative increase in levels of 2-hydroxylation pathway metabolites, or in the ratio of 2-hydroxylation:16-hydroxylation pathway metabolites, were associated inversely with breast cancer risk. These associations varied by total estrogen levels, with the largest risk reductions occurring in women in the highest tertile. With appropriate validation, these findings suggest opportunities for breast cancer prevention by modifying individual estrogen metabolism profiles through either lifestyle alterations or chemopreventive strategies.
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Elevated levels of circulating estrogens are linked to breast cancer risk among postmenopausal women but little is known about the importance of estrogen metabolism. A recently developed liquid ...chromatography tandem mass spectrometry-based method (LC-MS/MS) measuring a panel of 15 estrogen metabolites (EM) has been evaluated in one study, linking high levels of 2-pathway metabolites relative to the parent estrogens to reduced breast cancer risk. We analyzed this panel of EM in a nested case-control study of postmenopausal breast cancer.
Between 1977 and 1987, 6,915 women provided blood samples to the Columbia Missouri Serum Bank and were followed for incident breast cancer through December 2002. We studied 215 postmenopausal breast cancer cases and 215 matched controls who were postmenopausal and not using exogenous hormones at the time of blood draw. EM were examined individually, grouped by pathway (hydroxylation at the C-2, C-4 or C-16 positions of the steroid ring) and by ratios of the groupings. Logistic regression models controlling for matching and breast cancer risk factors were used to calculate quartile-specific odds ratios (ORs) and 95% CIs.
Significant elevated risks were not observed for individual EM, except for quartiles of 16-epiestriol (P trend = 0.07). The OR for total EM, the parent estrogens estrone and estradiol, and 2-pathway catechol EM (2-hydroxyestrone and 2-hydroxyestradiol) were elevated but the trends were not statistically significant. Among 2-pathway metabolites, risks for the highest levels of 2-hydroxyestrone-3-methyl ether and 2-methoxyestradiol were reduced; ORs for women in the highest versus lowest quartiles were 0.57 (95% CI = 0.33 to 0.99) and 0.53 (95% CI = 0.30 to 0.96), respectively. Overall, women with higher levels of 2-pathway EM had a reduced risk of breast cancer, which remained after accounting for levels of parent EM, 4-pathway EM and 16-pathway EM (all trends, P <0.11).
Women with more extensive hydroxylation along the 2-pathway may have a reduced risk of postmenopausal breast cancer. Further studies are needed to clarify the risks for specific EM and complex patterns of estrogen metabolism. This will require aggregation of EM results from several studies.
Nutrition labeling on food packages is increasingly found to promote healthier food choices associated with lower risk of chronic kidney disease (CKD). To examine associations between nutrition ...labels use and CKD risk, we conducted a nationally representative cross-sectional study of 32,080 adults from the 2008−2019 Korean National Health and Nutrition Examination Survey. Nutrition labels use was collected via self-reported questionnaires. Ascertainment and severity of CKD was determined by estimated glomerular filtration rate or proteinuria. In multivariable-adjusted (MV) logistic regression models, increasing awareness and use of nutrition labels was significantly associated with lower CKD risk (MV-adjusted OR “nutrition labels aware and use” group vs. “nutrition labels unaware” group 95% CIs: 0.75 0.59−0.95, Ptrend:0.03). This inverse association varied with CKD’s risk of progression, with 21% and 42% reduced risk observed for CKD subtypes with “moderate” and “high” risk of progression, respectively (all Ptrend ≤ 0.04). Furthermore, the nutrition labels use and CKD risk association significantly differed by age, with 35% reduced risk observed in the older group aged 49 years or older, but not in the younger group (Pinteraction < 0.001). Our results suggest increasing perception and use of nutrition labels may contribute to CKD prevention and its early asymptomatic progression, especially in older adults.
Antimüllerian hormone (AMH) is extensively studied in ovarian aging and pathology; however, little is known about correlates in healthy premenopausal women. We found that AMH levels are strongly ...inversely associated with age and differed significantly between oral contraceptive pill users and nonusers, whereas no significant associations were seen between AMH and other clinical, behavioral, and anthropometric characteristics and laboratory variables, making it an attractive hormone for clinical applications.
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