Abstract
The majority of leisure time is spent in sedentary behaviors such as television viewing. Studies have documented that prolonged leisure-time sitting is associated with higher risk of ...mortality—total, cardiovascular disease, cancer, and “all other causes”—but few have examined the “other” causes of death in detail. To examine associations of leisure-time sitting with risk of specific causes of death, we analyzed data from the Cancer Prevention Study II (CPS-II) Nutrition Cohort, a prospective US cohort including 127,554 men and women who were free of major chronic disease at study entry, and among whom 48,784 died during 21 years of follow-up (1993–2014; median follow-up, 20.3 years, interquartile range, 4.6 years). After multivariable adjustment, prolonged leisure-time sitting (≥6 vs. <3 hours per day) was associated with higher risk of mortality from all causes, cardiovascular disease (including coronary heart disease and stroke-specific mortality), cancer, diabetes, kidney disease, suicide, chronic obstructive pulmonary disease, pneumonitis due to solids and liquids, liver, peptic ulcer and other digestive disease, Parkinson disease, Alzheimer disease, nervous disorders, and musculoskeletal disorders. These findings provide additional evidence for associations between a broad range of mortality outcomes and prolonged sitting time. Given the pervasive nature of sitting in the contemporary lifestyle, this study further supports the recommendation that encouraging individuals to reduce sedentary time may provide health benefits.
Healthy diet patterns are associated with lower risk of cancer and other chronic diseases. Metabolomics has the potential to expand dietary biomarker development to include dietary patterns, which ...may provide a complement or alternative to self-reported diet.
This study examined the correlation of serum untargeted metabolomic markers with 4 diet pattern scores—the alternate Mediterranean diet score (aMED), alternate Healthy Eating Index (AHEI)-2010, the Dietary Approaches to Stop Hypertension (DASH) diet, and the Healthy Eating Index (HEI)-2015—and used multivariate methods to identify discriminatory metabolites for each pattern.
Among 1367 US postmenopausal women with serum metabolomic data in the Cancer Prevention Study-II Nutrition Cohort, we conducted partial correlation analysis, adjusted for demographic and lifestyle variables, to examine cross-sectional correlations between serum metabolomic markers and healthy diet pattern scores. In a randomly selected “training” set (50%), we conducted orthogonal partial least-squares discriminant analysis to identify metabolites that discriminated the top from bottom diet score quintiles. Combinations of metabolites with a variable importance in projection (VIP) score ≥2.5 were tested for predictability in the “testing” set based on the use of receiver operating characteristic curves.
Out of 1186 metabolites, 32 unique metabolites were considered discriminatory based on a VIP score ≥2.5 in the training dataset with some overlap across scores (aMED=16; AHEI=17; DASH=13; HEI=12). Spearman partial correlation analyses, applying a cut-point (|r|≥0.15) and Bonferroni correction (P<1.05×10−5), identified similar key metabolites. The top 5 metabolites for each pattern mostly distinguished high compared with low scores; 4 of the 5 (fish-derived) metabolites were the same for aMED and AHEI, 2 of which were identified for HEI; 4 DASH metabolites were unique.
Metabolomic methods that used a split-sample approach identified potential biomarkers for 4 healthy diet patterns. Similar metabolites across scores reflect fish consumption in healthy dietary patterns. These findings should be replicated in independent populations.
Research examining the effects of historical redlining on present-day health outcomes is often complicated by the misalignment of contemporary census boundaries with the neighborhood boundaries drawn ...by the US Home Owners' Loan Corporation (HOLC) in the 1930s. Previous studies have used different approaches to assign historical HOLC grades to contemporary geographies, but how well they capture redlining exposure is unknown.
Our analysis included 7711 residences identified in the Multiple Listing Service database in Atlanta, Georgia (2017-2022). We evaluated the classification of HOLC grade assignment (A, B, C, D, or ungraded) when assigning exposure under four area-level approaches (centroid, majority land area, weighted score, and highest HOLC) compared with using complete address data (gold standard). We additionally compared approaches across three 2020 census geographies (tract, block group, and block).
When comparing the use of census tracts to complete address data, sensitivity was highest for the weighted score approach, which correctly identified 77% of residences in truly A-D graded neighborhoods as compared with the majority land area (44%), centroid (54%), and highest HOLC (59%) approaches. Regarding specificity, the majority land area approach best-classified residences in truly ungraded neighborhoods (93%) as compared with the weighted score (65%), centroid (81%), and highest HOLC (54%) approaches. Classification improved regardless of approach when using census block compared with the census tract.
Misclassification of historical redlining exposure is inevitable when using contemporary census geographies rather than complete address data. This study provides a framework for assessing spatial misalignment and selecting an approach for classification.
ABSTRACT
Purpose
Nearly half of the 3.5 million female breast cancer survivors in the US are aged 65 years or older at diagnosis, yet little is known about associations of obesity and physical ...activity with breast cancer-specific mortality (BCSM) among older survivors.
Methods
Between 1992 and 2013, 5254 women in the Cancer Prevention Study-II Nutrition Cohort were diagnosed with local or regional breast cancer among whom 1771 deaths (505 breast cancer deaths) occurred. Multivariable Cox proportional hazards regression models were used to examine associations of pre- and post-diagnosis body mass index (BMI) and moderate–vigorous physical activity (MET-hours/week) with mortality outcomes stratified by age at diagnosis (<65, ≥65 years).
Results
Among women ≥65 years of age at diagnosis (
n
= 4226), pre- and post-diagnosis BMI (per 5 kg/m
2
) were associated with a higher risk of BCSM (pre-diagnosis, HR 1.27, 95% CI 1.14–1.41; post-diagnosis, HR 1.19, 95% CI 1.04, 1.36); neither pre- nor post-diagnosis physical activity was associated with BCSM. Among women <65 years of age at diagnosis (
n
= 1028), BMI at both time points were not significantly associated with BCSM; however, there was a significant inverse trend of post-diagnosis physical activity with BCSM (
P
-trend = 0.01). Among both age groups, BMI and physical activity, regardless of when assessed, were significantly associated with all-cause mortality.
Conclusions
Higher BMI, pre- or post-diagnosis, was associated with a higher risk of BCSM in older patients, independent of comorbidities and stage at diagnosis. Weight management should be discussed even with women aged 65 years or older to lower rates of BCSM.
Crown-like structures in breast adipose tissue (CLS-B), composed of necrotic adipocytes encircled by macrophages, are associated with obesity and hypothesized to worsen breast cancer prognosis; ...however, data are sparse, particularly in multi-racial populations.
We assessed specimens for CLS-B from 174 African-American and 168 White women with stage I-III breast cancer treated by mastectomy. Benign breast tissue from an uninvolved quadrant was immunohistochemically stained for CD68 to determine CLS-B presence and density (per cm
of adipose tissue). Demographic and lifestyle factors, collected via medical record review, were analyzed for associations with CLS-B using logistic regression. Multivariable Cox proportional hazards models were used to compute hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between CLS-B and overall (OS) or progression-free (PFS) survival.
Detection of any CLS-B was similar between African-American (32%) and White (29%) patients with no evidence of an association between race and CLS-B in multivariable models (OR = 0.82, 95% CI = 0.49-1.36). Detection of CLS-B was associated with obesity (OR = 4.73, 95% CI = 2.48-9.01) and age ≥ 60 years at diagnosis (OR = 1.78, 95% CI = 0.99-3.21). There was some evidence of associations with parity and current smoking status. Detection of CLS-B was not associated with OS (HR = 1.02, 95% CI = 0.55-1.87) or PFS (HR = 0.99, 95% CI = 0.59-1.67).
Our results show a strong, positive association between BMI and CLS-B in non-tumor tissue similar to previous findings. Detection of CLS-B did not vary by race and was not associated with worse OS or PFS.
Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that facilitates the adaptation of cancer cells to hypoxic conditions and may be prognostic of breast cancer recurrence. We evaluated ...the association of HIF-1α expression with breast cancer recurrence, and its association with timing of breast cancer recurrence.
In this population-based case-control study, we included women diagnosed with stage I-III breast cancer between 1985 and 2001, aged 35-69 years, registered in the Danish Breast Cancer Group. We identified 541 cases of breast cancer recurrence among women with estrogen receptor (ER)-positive disease who were treated with tamoxifen for at least 1 year (ER+ TAM+). We also enrolled 300 breast cancer recurrence cases among women with ER-negative disease, not treated with tamoxifen, who survived at least 1 year (ER-/TAM-). Controls were recurrence-free breast cancer patients at the time of case diagnosis, matched to recurrence cases on ER/TAM status, date of surgery, menopausal status, cancer stage, and county of residence. Expression of HIF-1α was measured by immunohistochemistry on tissue microarrays. We fitted logistic regression models to compute odds ratios (ORs) and 95% confidence intervals (CIs) associating HIF-1α expression with recurrence, and with timing of recurrence.
HIF-1α expression was observed in 23% of cases and 20% of controls in the ER+/TAM+ stratum, and in 47% of cases and 48% of controls in the ER-/TAM- stratum. We observed a near-null association between HIF-1α expression in both ER/TAM groups (ER+/TAM+ OR = 1.21, 95%CI 0.88, 1.67 and ER-/TAM- OR = 0.97, 95%CI 0.68, 1.39). HIF-1α expression was not associated with time to recurrence among women in the ER+/TAM+ stratum, but was associated with early recurrence among women in the ER-/TAM- stratum.
In this study, HIF-1α expression was not associated with breast cancer recurrence overall but may be associated with early recurrence among women diagnosed with ER- breast cancer.
Large prospective cohort studies need to confirm the associations between recreational physical activity (PA), including the most common type—walking, and prostate cancer–specific mortality (PCSM) ...among prostate cancer patients.
To investigate the associations of recreational PA, reported before and after diagnosis, with PCSM, overall and by tumor risk category.
In a prospective cohort study conducted in the USA, men diagnosed with nonmetastatic prostate cancer between 1992/1993 and June 2011 were followed for mortality until 2012. Patients were included in pre- (n=7328) and/or postdiagnosis (n=5319) analyses.
Cox proportional hazards models were used to assess PCSM with recreational PA.
A total of 454 and 261 prostate cancer deaths occurred during pre- and postdiagnosis follow-up, respectively. Prior to diagnosis, engaging in ≥17.5 metabolic equivalent hours per week (MET-h/wk) of recreational PA, compared with 3.5–<8.75 MET-h/wk, was associated with a significant 37% lower risk of PCSM (hazard ratio: 0.63, 95% confidence interval: 0.43–0.91, p trend=0.03) only among men with lower-risk tumors (Gleason score 2–7 and T1–T2; p interaction=0.02). A similar result was seen for walking but not for other recreational PA. After diagnosis, the same comparison (≥17.5 vs 3.5–<8.75 MET-h/wk) was associated with a significant 31% lower risk of overall PCSM (hazard ratio: 0.69, 95% confidence interval: 0.49–0.95, p trend=0.006), which did not differ by tumor risk category. Postdiagnosis walking had a suggestive inverse association with PCSM (p trend=0.07). These results were observational and may not be generalized to patients with metastatic prostate cancer. Residual confounding due to a higher screening rate among men with lower-risk tumors cannot be ruled out.
The findings provide additional evidence for prostate cancer survivors to adhere to PA recommendations, and support clinical trials of exercise among prostate cancer survivors with progression or mortality as outcomes.
In a large follow-up study of men diagnosed with nonmetastatic prostate cancer, those who exercise more after diagnosis had a lower risk of dying from prostate cancer.
In this large follow-up study of men diagnosed with nonmetastatic prostate cancer, engaging in at least 17.5 metabolic equivalent hours or 5h of moderate-intensity activity per week may improve prostate cancer–specific survival and overall survival.
Obesity is an established risk factor for postmenopausal breast cancer and has been linked to worse breast cancer prognosis, most clearly for hormone receptor-positive breast cancers. The underlying ...mechanisms of the obesity-breast cancer association are not fully understood, but growing evidence points to the breast adipose tissue microenvironment playing an important role. Obesity-induced adipose tissue dysfunction can result in a chronic state of low-grade inflammation. Crown-like structures of the breast (CLS-B) were recently identified as a histologic marker of local inflammation. In this review, we evaluate the early evidence of CLS-B in breast cancer. Data from preclinical and clinical studies show that these inflammatory lesions within the breast are associated with local NF-κB activation, increased aromatase activity, and elevation of pro-inflammatory mediators (TNFα, IL-1β, IL-6, and COX-2-derived PGE
)-factors involved in multiple pathways of breast cancer development and progression. There is also substantial evidence from epidemiologic studies that CLS-B are associated with greater adiposity among breast cancer patients. However, there is insufficient evidence that CLS-B impact breast cancer risk or prognosis. Comparisons across studies of prognosis were complicated by differences in CLS-B evaluation and deficiencies in study design, which future studies should take into consideration. Breast adipose tissue inflammation provides a plausible explanation for the obesity-breast cancer association, but further study is needed to establish its role and whether markers such as CLS-B are clinically useful.
Abstract Background Few studies have examined the association between chronic methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (PA) co-infection and health outcomes ...despite evidence that these pathogens alone contribute to higher morbidity and mortality in cystic fibrosis (CF). This study examines outcomes among CF patients with chronic MRSA and PA co-infection compared with patients with either or neither of these organisms. Methods CF patients attending the care center in Atlanta, GA from 2007–2013 comprised the study cohort. Chronic co-infection was defined as > 50% PA + cultures and > 50% MRSA + cultures and modeled as time-varying. The rate of decline in lung function (FEV1 ) and the rate of IV treatments were the main outcomes. Results Among all patients (N = 354), chronic co-infection was associated with a significantly more rapid rate of FEV1 decline compared with patients with chronic PA alone adjusted difference: − 0.60% predicted/year (− 1.13, − 0.08) and chronic MRSA alone adjusted difference: − 0.89% predicted/year (− 1.56, − 0.22). Rate of IV treatments was significantly higher among patients with chronic co-infection compared with patients with chronic PA alone adjusted IRR: 1.24 (1.01, 1.52) and chronic MRSA alone adjusted IRR: 1.34 (1.03, 1.74). Conclusions Data from the Atlanta Care Center suggest that chronic MRSA and PA co-infection may be associated with increased rate of lung function decline and rate of intravenous antibiotics compared with patients with either pathogen alone.
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