Neighborhood Environment, DNA Methylation, and Presence of Crown-Like Structures of the Breast
Notice bibliographique
Résumé
Importance: Inflammation impacts cancer risk and tumor biological processes, yet studies linking it to social and environmental risk factors are lacking. Objective: To investigate the association of neighborhood deprivation and air pollution with breast adipose inflammation as well as the association between crown-like structures of the breast (CLS-B) and DNA methylation in Black and White women. Design, Setting, and Participants: This cross-sectional study analyzed women with and without breast cancer participating in the National Cancer Institute-Maryland Breast Cancer Study, most of whom were recruited between January 1, 1993, and December 1, 2003, from the University of Maryland Medical Center and surrounding hospitals in the Baltimore, Maryland, area. A small subset of the sample was recruited between March 27, 2012, and November 27, 2017. Noncancerous breast tissue was collected from women who underwent reduction mammoplasty or breast cancer surgery. Statistical analyses were conducted between May and August 2024. Exposures: Two socioenvironmental exposures were examined: air pollution (specifically, fine particulate matter less than 2.5 μm in diameter [PM2.5]) and neighborhood deprivation (measured with Neighborhood Deprivation Index [NDI]). Participant geocodes were linked to 2000 US Census data to calculate PM2.5 concentrations (total mass [μg/m3]) and NDI. Main Outcomes and Measures: Breast tissues underwent immunohistochemical staining for pan-macrophage marker CD68 to detect 2 outcomes: CLS-B and adipose-associated macrophages. CLS-B and adipose-related macrophages were assessed by pathologists using artificial intelligence-assisted and manual approaches. Covariate-adjusted logistic regression models were used to ascertain associations between PM2.5 and NDI (exposures) and presence or absence of CLS-B (outcome); CD68-positive adipose macrophages were modeled as a dichotomous high or low variable. Covariate-adjusted linear regression was used to identify associations between CLS-B (exposure) and DNA methylation (outcome). Results: The cohort included 205 participants (127 Black [62.0%], 78 White [38.0%] women; mean [SD] age, 48.7 [13.3] years). Women with vs without CLS-B had higher median (IQR) body mass index (calculated as weight in kilograms divided by height in meters squared; 35.5 [30.5-40.9] vs 31.8 [26.6-36.4]; P = .02). Higher levels of PM2.5 (odds ratio [OR], 2.32; 95% CI, 1.12-4.78; P = .02) and NDI (OR, 1.21; 95% CI, 1.02-1.43; P = .03) were associated with presence of CLS-B overall; findings were still significant among Black women (PM2.5: OR, 2.64 [95% CI, 1.10-6.33], P = .03; NDI: OR, 1.22 [95% CI, 1.01-1.48], P = .04) but were not statistically significant among White women (PM2.5: OR, 1.65 [95% CI, 0.45-5.99], P = .45; NDI: OR, 1.19 [95% CI, 0.83-1.70], P = .35). Higher PM2.5 concentration was associated with increased macrophage infiltration (OR, 2.11; 95% CI, 1.24-3.60; P = .006), with similar outcomes by race. The top 2 significant differentially methylated CpG sites by CLS-B status were SAR1B (β = 0.01; 95% CI, 0.01-0.02; P < .001) and IL2RB (β = -0.04; 95% CI, -0.05 to -0.02; P < .001). Significant interaction was observed between CLS-B status and race for IL2RB methylation levels (β = -0.03; 95% CI, -0.04 to -0.01; P for interaction <.001). Conclusions and Relevance: This cross-sectional study uncovered an association between neighborhood-level social and environmental risk factors and breast tissue inflammation. The findings help inform efforts to reduce racial and socioeconomic disparities in breast cancer and improve health equity for socially vulnerable populations.
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».