Neighborhood Environment, DNA Methylation, and Presence of Crown-Like Structures of the Breast
Bibliographic record
Abstract
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".