Studies linking mitochondrial DNA (mtDNA) variants to cognition yielded inconsistent findings, and the underlying mechanisms remain unclear. We investigated whether mtDNA heteroplasmic variants were associated with cognitive outcomes, including the Montreal Cognitive Assessment (MoCA), in 197 late midlife adults from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort with complete data. MtDNA was sequenced from blood using targeted deep sequencing. Adjusted linear and mixed-effects models examined the associations by functional regions, genes, total variant burden, nonsynonymous variants, and control regions. Heteroplasmic variants in the control region (β = -0.44, 95

BackgroundStudying social determinants of health (SDOH) in air pollutant-related bone loss among aging women may help identify bone health disparities, design preventive strategies, and inform policy. Prolonged exposure to air pollution is associated with decreased bone mineral density (BMD) and increased fracture risk in later life. However, the extent to which socioeconomic status (SES) contributes to pollution-related bone damage remains unclear.MethodsWe estimated the extent to which social determinants of health (SDOH) modify the associations of nitrogen oxides (NOx) and sulfur dioxide (SO2)-induced bone damage. We analyzed the Women's Health Initiative (WHI) data from the randomized clinical trial (RCT) (n = 4,202) and the observational study (OS) (n = 4,839), totaling 9,041 women. Ambient concentrations of nitrogen dioxide (NO2), nitrogen oxide (NO), and SO2, averaged over 1-, 3-, and 5-year periods preceding bone mineral density (BMD) assessment, were the exposures. Individual- and neighborhood-level SDOH (self-reported educational attainment, annual family income, and neighborhood-level socioeconomic status (nSES) were evaluated as potential effect modifiers. BMD at the lumbar spine, total hip, and whole body were modeled as outcomes using linear mixed models.ResultsA 10% increase in NO2 was suggestively associated with 1.4–3.8 times greater BMD loss in low vs. high nSES participants across all sites. For example, 1-year lumbar spine BMD loss per 10% NO2 increase was β = −0.047 (95% CI, −0.066 to −0.027) in the low nSES compared with β = −0.013 (95% CI, −0.023 to −0.001) in the high nSES group (p-interaction = 0.001). Similarly, suggestive associations were also observed for NO. nSES interactions were null for SO2. For income, NO was suggestively associated with lumbar spine bone loss across all exposure periods, whereas only the 3-year average NO2 exposure was suggestively associated with whole-body BMD (p = 0.048). Again, no interaction was observed for SO2. Participants with lower education showed greater NO-related lumbar spine bone. SO2 showed the opposite pattern at multiple sites, while NO2 showed no associations.ConclusionNeighborhood-level analyses revealed suggestive associations between bone mineral loss and a broader range of air pollutants. Reducing social inequities may improve the bone health of older women living in areas with high air pollution. Additional studies are needed to generalize the findings to younger women and men, as only older women were analyzed.

Abstract Abstract Background: Non-small cell lung cancer (NSCLC) is increasing worldwide, yet the environmental and mechanistic contributors driving tumor development and aggressiveness remain poorly defined. Metals and trace elements—ubiquitously present in air pollution—can induce oxidative stress, potentially generating DNA damage that remodels tumor metabolism and promotes malignancy. We evaluated the feasibility of integrating metal profiling in malignant and normal NSCLC tissues and identified preliminary correlations between trace elements and malignancy status. Methods: Ten OCT-embedded lung adenocarcinoma cases from an urban cohort of patients attended and biobanked at the Mount Sinai Biorepository underwent laser-capture microdissection to isolate paired tumor and adjacent normal tissue. Twenty-three metals and trace elements were quantified using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) following nitric acid digestion. Logistic regression models (unadjusted due to sample size) were used to evaluate associations with tumor status. Linear regressions were used for tumor size. Results: Tumor tissue demonstrated distinct metal signatures. Magnesium (Mg) and selenium (Se) were significantly enriched in tumors (Mg: Odds ratio [OR]=4.79, 95% Confidence Interval [95% CI]: 1.10-20.82; Se: OR=18.93, 95% CI: 1.48-242.44), while nickel (Ni) and zinc (Zn) showed positive trends toward tumor accumulation. Iron (Fe) was markedly higher in normal tissue. Additional analyses revealed inverse associations between tumor size and chromium (Cr; β = -1.34, 95%CI: -2.41, -0.27, p = 0.02*), manganese (Mn; β = -1.06, 95%CI: -2.32, 0.199, p = 0.09*), and cesium (Cs; β = -1.10, 95%CI: -2.16, -0.04, p = 0.04*). Conclusions: Preliminary data demonstrate the feasibility of multiple metal and trace element quantification in NSCLC tissues, revealing potential specific perturbations associated with tumor presence and aggressiveness. The observed enrichment of Mg, Se, and Ni in tumors supports a potential mechanistic link between metal exposure, trace element imbalance, and malignant phenotypes, which may contribute to NSCLC tumorigenesis in urban populations. Ongoing analyses will integrate mitochondrial mtDNA heteroplasmy variants from these NSCLC samples to elucidate metal-mitochondrial interactions driving tumor biology. Citation Format: Diddier Prada, Manish Arora, Julio landero, Jamshid Abdul Ghafar, Rachel Brody, Oscar Arrieta, Fred R. Hirsch. Trace metal signatures in non-small cell lung cancer: A pilot study of patients attended at Mount Sinai Hospital in New York City [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4736.

Lung cancer in never smokers (LCINS) disproportionately affects younger women and East Asian populations and is characterized by distinct genetic susceptibility, environmental exposures, and molecular alterations. However, never smokers remain excluded from current screening guidelines despite rising incidence and identifiable high-risk subgroups. Family history confers substantial risk, with affected first-degree relatives having 1.7-fold higher incidence, whereas genome-wide association studies and polygenic risk scores further refine genetic susceptibility. Female sex and Asian ethnicity are primary independent risk factors, exceeding family history in multivariable analysis. Asian never smokers have a 2.3-fold higher baseline incidence of lung cancer than non-Asian never smokers, and Asian female never smokers exhibit lung cancer detection rates comparable to Asian male ever smokers. Screening trials in never smokers demonstrated detection rates comparable to smoker-based trials, suggesting certain demographic subgroups may reach risk thresholds where screening could be beneficial. Environmental exposure to particulate matter less than or equal to 2.5 μm in aerodynamic diameter increases LCINS incidence and mortality in East Asian populations where both exposure to particulate matter less than or equal to 2.5 μm in aerodynamic diameter and EGFR mutation rates are elevated. Recent evidence implicates mitochondrial DNA mutations in LCINS susceptibility among Asian never smokers, suggesting integration of environmental exposures and molecular biomarkers may improve risk stratification for screening. The high prevalence of actionable oncogenic drivers in LCINS underscores the importance of early detection, as these tumors benefit from targeted therapies whereas immune checkpoint inhibitors responses are often lower. This review summarizes LCINS epidemiology, genetic susceptibility, molecular alterations, environmental risk factors, and tumor immunology, highlighting the need for greater focus on this underrecognized and growing patient population.

Abstract Background: Myxoid liposarcoma (MLS), a genetically stable soft-tissue sarcoma driven by FUS-DDIT3 fusions, harbors additional somatic alterations contributing to progression and microenvironmental adaptation. These remain underexplored in non-European populations. Methods: We conducted whole-genome sequencing (WGS) on tumors from 56 Mexican MLS patients using a standardized pipeline (BWA-MEM2 alignment, GATK Mutect2 variant calling, VEP annotation). We analyzed somatic SNVs/indels, mutational signatures, gene-specific clustering (OncodriveCLUST), and co-occurrence patterns via cohort-level MAF files. Results were visualized with oncoplots and positional analyses. Results: Tumors exhibited moderate mutational burden (median 6.4 × 104 variants/sample), dominated by missense substitutions and C>T transitions (SBS1 and SBS5 signatures). Recurrent alterations enriched in structural genes (e.g., MUC3A, MUC4, MUC5AC, MUC16, AHNAK2, FLG, TTN, ZNF) suggested extracellular and cytoskeletal remodeling. Key oncogenic hits included PIK3CA (89%; activating p110α variants), TP53 (98%; DNA-binding loss-of-function), RB1 (87%; RB_A/RB_B disruptions), and ATRX (98%; helicase/ADD domain mutations), implicating PI3K-TP53-RB1-ATRX pathway cooperation and telomere instability. Co-occurrence clustered in adhesion/matrix genes without exclusivity, while OncodriveCLUST hotspots (DEFB4A, DEFB107A, USP17L17, FOXD4L4) pointed to immune and epigenetic modulation. Conclusions: Beyond FUS-DDIT3 fusions, MLS features coordinated PI3K-TP53-RB1-ATRX alterations, structural remodeling, and immune hotspots. This first WGS study in Mexican (and one of few in Latin American) MLS patients establishes a genomic atlas for diverse populations, informing targeted therapies like PI3K inhibitors. Citation Format: Jonathan Gonzalez, Hayde Caro-Sánchez, Dorian Y. García-Ortega, Andrea Ramírez, Rodrigo Cruz-Nieto, Claudia García-Cuellar, Diddier Prada. Comprehensive whole-Genome profiling reveals Cooperative PI3K-TP53-RB1-ATRX pathway alterations and immune-modulatory drivers in myxoid liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 6292.

e17518 Background: Cervical cancer remains a significant global health burden, particularly in low- and middle-income countries, where limited radiotherapy infrastructure restricts access to standard treatment. Although concurrent chemoradiotherapy is the standard of care, hypofractionated radiotherapy may improve treatment efficiency while maintaining oncologic outcomes. Our purpose is to compare pathologic response outcomes between hypofractionated and standard radiotherapy in patients with locally advanced cervical cancer. Methods: Pathologic response was evaluated in patients with FIGO stage IB3–IIIC1 cervical cancer enrolled in a phase II randomized trial. Patients received concurrent chemotherapy with either standard external-beam radiotherapy (50 Gy in 25 fractions) or hypofractionated radiotherapy (37.5 Gy in 15 fractions), followed by radical hysterectomy and bilateral pelvic lymphadenectomy. Pathologic response and lymph node involvement were compared between groups using chi-square or Student’s t tests, as appropriate. A p value < 0.05 was considered statistically significant. Results: Ninety-three patients were included (50 standard fractionation; 43 hypofractionation). Baseline clinical and tumor characteristics were balanced between groups. Squamous cell carcinoma was the most common histology (84%). Complete pathologic response was observed in 48% of patients in the standard arm and 35% in the hypofractionated arm, while residual microscopic disease was identified in 38% and 44%, respectively ( p = 0.46). Additional treatment due to partial response was required in 14% of patients receiving standard fractionation and 21% receiving hypofractionation. Adverse pathologic features prompting further treatment included residual tumor >1 cm, lymphovascular space invasion, deep stromal invasion, and positive surgical margins. The mean number of lymph nodes resected was similar between groups (14 vs. 15; p = 0.291). Among 1,399 lymph nodes examined, 0.85% were positive on final pathology. Conclusions: Pathologic response following hypofractionated radiotherapy appeared comparable to that achieved with standard fractionation. While hypofractionation is not currently standard for cervical cancer, these findings suggest it may represent a feasible alternative in settings with limited radiotherapy capacity. Larger studies with longer follow-up are required to further assess efficacy, safety, and pathological response patterns. Clinical trial information: NCT03750539 .

5534 Background: Cervical cancer remains a significant global health burden, particularly in low- and middle-income countries where access to radiotherapy is often limited. While concurrent chemoradiotherapy is the standard of care, hypofractionated radiotherapy has emerged as a potential strategy to improve treatment efficiency without compromising outcomes. Our purpose was to assess the impact of hypofractionated radiotherapy on quality of life in comparison with conventional fractionation in patients with locally advanced cervical cancer. Methods: Health-related quality of life was evaluated using EORTC QLQ-C30 and QLQ-CX24 questionnaires in patients with FIGO stage IB3–IIIC1 cervical cancer enrolled in a phase II randomized trial. All patients received concurrent chemotherapy and were assigned to either standard external-beam radiotherapy (50 Gy in 25 fractions) or hypofractionated radiotherapy (37.5 Gy in 15 fractions), followed by radical hysterectomy with bilateral pelvic lymphadenectomy. QoL scores were calculated using standard EORTC methodology. Higher scores indicate better functioning or greater symptom burden, and changes were interpreted based on established thresholds for clinical relevance. Outcomes were compared between groups across predefined time points using ANOVA. Statistical significance was defined as p < 0.05. Results: A total of 91 patients were included (49 standard fractionation, 42 hypofractionation). No significant differences in global QoL were observed between treatment groups. However, QoL varied significantly over time, with the greatest deterioration occurring between completion of concomitant chemoradiotherapy and surgery. Quality-of-life scores recovered to baseline levels by three months after treatment completion in both groups. Conclusions: Hypofractionated radiotherapy was not associated with worse quality-of-life outcomes compared with conventional fractionation. These findings support hypofractionation as a feasible alternative for locally advanced cervical cancer, particularly in resource-limited settings. Further studies with larger cohorts and longer follow-up are warranted to confirm these results. Clinical trial information: NCT03750539 . Comparison of key health-related quality-of-life domains by treatment arm. Domain BaselineStd*/ Hypo& End QT/RTStd / Hypo Post-SurgeryStd / Hypo 3 MonthsStd / Hypo p value Global Health Status / QoL 66.9 (23.7) / 65.8 (21.0) 65.7 (20.7) / 64.6 (17.0) 70.5 (18.5) / 64.0 (18.3) 79.1 (12.5) / 74.4 (21.7) 0.497 Physical Functioning 81.6 (19.7) / 88.0 (14.6) 80.2 (18.6) / 82.2 (20.8) 75.2 (20.5) / 79.0 (17.5) 86.4 (19.4) / 86.8 (13.6) 0.216 Nausea and Vomiting 87.1 (21.2) / 83.8 (27.8) 72.4 (30.5) / 67.2 (28.5) 82.6 (23.3) / 88.3 (21.0) 94.8 (10.2) / 91.1 (16.8) 0.001 Diarrhea 90.1 (15.5) / 86.6 (28.5) 77.7 (20.6) / 67.7 (28.3) 81.4 (21.3) / 84.4 (25.8) 92.5 (14.1) / 91.1 (14.9) 0.001 Mean (SD) scores using EORTC QLQ-C30 and CX-24.

Radon is a radioactive gas and a lung carcinogen, yet lacks established blood biomarkers for long-term exposure. We aimed to identify circulating metabolomic and exposomics signatures correlated with reconstructed radon-222 exposure. Metabolites and chemical exposomes were profiled using liquid and gas chromatography-high-resolution mass spectrometry from plasma (n=80). Batch effects were corrected using ComBat, and network and pathway analyses were performed using xMWAS and MetaboAnalyst, respectively. A total of 124 metabolites were correlated with radon, including 41 positive correlations. The strongest positive and negative associations involved unidentified features. Network analysis identified six communities, five of which were directly related to radon. Fatty acyls were the most represented class, followed by benzene derivatives and hydroxy acids and derivatives. Pathway analysis showed enrichment in linoleate, fatty acid, and amino acid metabolism. Our findings demonstrate that integrating metabolomic and chemical exposomes may help identify sensitive biomarkers for radon exposure. We recommend further studies to investigate these pathways in greater mechanistic detail to understand the health effects of radon.

BACKGROUND:We investigated whether adulthood socioeconomic status (SES) mediates the association between childhood SES and biological aging in a longitudinal cohort (N = 359). METHODS:SES was measured using composite scores from prospective measures in childhood and at age 50. Peripheral blood DNA methylation (DNAm) was measured at approximately 50 years of age. DNAm age acceleration (AA) was quantified for DNAm "clocks" (Horvath, Hannum, PhenoAge, GrimAge) and a DNAm pace-of-aging measure (DunedinPACE). Linear regression was used to evaluate the associations between SES at each life stage and DNAm AA. Adulthood SES was evaluated as a mediator between childhood SES and DNAm AA using marginal structural models. RESULTS:Compared to high childhood SES, low childhood SES was associated with AA for GrimAge (β = 0.99, 95% confidence interval [CI]: 0.08, 1.91) and DunedinPACE (β = 0.05, 95% CI: 0.02, 0.08). Low adulthood SES, compared to high adulthood SES, was also associated with AA for GrimAge (β = 2.31, 95% CI: 1.35, 3.28) and DunedinPACE (β = 0.05, 95% CI: 0.02, 0.08). The association between childhood SES and both clocks were partially mediated by adulthood SES. No other clocks were associated with SES. CONCLUSION:Early and late-life socioeconomic conditions accelerate biological aging. Larger studies exploring mediators and interventions are needed for equitable aging mitigation.

Background:Up to 3.0% of women are diagnosed with endometrial cancer after hysterectomy for apparently benign conditions. There is controversy about the benefit of complementary lymphadenectomy in incidental endometrial cancer after hysterectomy. Objective:To evaluate the role complementary lymphadenectomy during a second surgery in the prognosis of patients with endometrial carcinoma. Study design:This was a retrospective cohort study of patients who were diagnosed with endometrial carcinoma from 2005 to 2019. Two groups were evaluated: patients who underwent a second surgery involving pelvic and/or para-aortic lymphadenectomy and patients who did not undergo surgical lymph node evaluation. Logistic regression was used to identify the factors associated with whether or not a complementary lymphadenectomy was performed. The Kaplan-Meier method was used to generate survival curves, and the log-rank test was used for comparisons. Univariate and multivariate analyses were performed with the Cox test. Results:Two hundred and sixty patients were included. Among them, 120 (46.15%) underwent complementary lymphadenectomy, and 140 (53.83%) did not. The factors associated with performing complementary lymphadenectomy in a second surgical procedure were higher grade, nonendometrioid histology and deep myometrial involvement. The factors associated with adjuvant treatment were high-grade histology, deep myometrial involvement, cervical involvement and extensive lymphovascular permeation. Complementary lymphadenectomy was not associated with adjuvant treatment (OR 0.85 95% CI 0.35-2.02), overall survival (Hazard Ratio (HR) 0.40 95% CI 1.16-1.00) or disease-free survival (HR 0.77 95% CI 0.38-1.59). Conclusions:No clear therapeutic or prognostic role was identified for complementary lymphadenectomy during a second surgery in patients with endometrial cancer. Although adjuvant therapy was more common in patients who underwent complementary lymphadenectomy, it was not independently associated with receiving adjuvant therapy. Individualizing treatment decisions remains important when considering a second surgical procedure.

OBJECTIVE:To evaluate the association between the prognostic nutritional index and the response to neoadjuvant chemotherapy in Mexican patients with epithelial ovarian cancer. METHODS:Retrospective analyses of 220 patients with epithelial ovarian cancer treated with neoadjuvant therapy. The cutoff points for the prognostic nutritional index at diagnosis and after neoadjuvant therapy were determined via receiver operating characteristic curves. Categorical variables were analyzed with the χ2 test, and multivariate analyses were performed with logistic regression. Disease-free survival and overall survival were analyzed via the Kaplan‒Meier method. RESULTS:The median age was 55 years (range; 28-82). The most common histology was high-grade serous carcinoma in 199 cases (90.5%), and 66.4% (n = 146) were International Federation of Gynecology and Obstetrics stage IIIC. The prognostic nutritional index cutoff points at diagnosis and after neoadjuvant chemotherapy for complete or optimal cytoreduction were 40.5 and 45, respectively. High prognostic nutritional index values were associated with higher rates of complete or optimal cytoreduction: 53.6% and 67.7%, respectively. Additionally, high prognostic nutritional index values were associated with platinum sensitivity. According to the multivariate analysis, a high prognostic nutritional index value (OR 6.6, p = .001) was an independent factor associated with complete or optimal cytoreduction. The median overall survival at 3 years was not reached in patients with high prognostic nutritional index values (p = .054 and p = .015). Disease-free survival was not significantly different for high versus low prognostic nutritional index values (p = .9). CONCLUSIONS:The prognostic nutritional index may be used as an independent prognostic biomarker for advanced epithelial ovarian cancer.

Ambient air pollution has been associated with bone damage. However, no studies have evaluated the metabolomic response to air pollutants and its potential influence on bone health in postmenopausal women. We analyzed data from Women’s Health Initiative (WHI) participants with plasma samples. Whole-body, TH, FN, and spine BMD were determined using DXA at enrollment and follow-up visits (years 1, 3, 6, and 9 visits; Y1, Y3, Y6, Y9, respectively). Geocoded, participant address-specific, daily particulate matter nitrogen oxide (NO), nitrogen dioxide (NO2), particulate matter ≤10 μm (PM10), and sulfur dioxide (SO2) concentrations were averaged over 1-, 3-, and 5-yr periods before plasma sampling for metabolomic assessments (at baseline and Y1 visit). The averages were then integrated using masked WHI participant identifiers. Statistical analyses included multivariable-adjusted linear mixed models, pathway analyses, and mediation modeling. At all averaging periods, NO, NO2, and SO2, but not PM10, were associated with taurine, inosine, and C38:4 phosphatidylethanolamine (PE). We found a partial potential mediation of C38:4 PE in the association between 1-yr average NO and LS BMD (p-value: .032). This is the first study suggesting phospholipids may partially mediate air pollution-related bone damage in postmenopausal women.

OBJECTIVE:Our retrospective study aimed to investigate the role of computed tomography (CT) using both the tomographic Fagotti index and the Sugarbaker peritoneal cancer index (PCI) in predicting the feasibility of optimal interval debulking surgery in epithelial ovarian cancer. METHODS:Patients with advanced ovarian cancer treated in our institution who were eligible for interval debulking surgery were identified and included in the study. A retrospective image collection was operated, and CT scan evaluations were conducted by 2 independent radiologists to establish both scores (Fagotti index and Sugarbaker PCI). The workflow included a third radiologist who resolved discrepancies. The receiver operating characteristics curve followed by the Youden J statistic was calculated to determine cutoff points that best differentiated complete/optimal versus suboptimal cytoreduction. The Fagotti index and Sugarbaker PCI cutoffs' accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were calculated and represented as 95% CIs. RESULTS:A total of 60 consecutive patients who had complete information in their charts with evaluable images and complete information about surgery were evaluated; of these, 35 had a complete/optimal interval debulking surgery. The receiver operating characteristic curve of the Fagotti index scoring system showed that a cutoff of ≥3 can identify 100% of inoperable patients. However, 29% of patients were falsely labeled as inoperable. A cutoff point of ≥5 avoids 88% of unnecessary laparotomies, reducing the rate of false inoperable designation from 29% to 17%. A Sugarbaker PCI of ≥8 predicts the risk of unnecessary laparotomies in 68%, with 26% falsely labeled as inoperable. The score of ≥7 is most effective in avoiding unnecessary surgeries (80%), but the chance of false positives increases from 26% to 32%. CONCLUSION:CT-based scoring systems used in the present work can help determine which patients with advanced ovarian cancer are suitable for interval debulking surgery with high precision. Future studies are needed to enhance accuracy, thereby amplifying the radiologists' competency in using a systematic CT-based scoring system.

Metal exposures are closely related to childhood developmental health. However, their effects on the childhood gut microbiome, which also impacts health, are largely unexplored using microbiome multiomics including the metagenome and metatranscriptome. This study examined the associations of fecal profiles of metal/element exposures with gut microbiome species and active functional pathways in 8- to 12-year-old children (N = 116) participating in the GESTation and Environment (GESTE) cohort study. We analyzed 19 stool metal and element concentrations (B, Na, Mg, Al, K, Ca, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Mo, Cd, Ba, and Pb). Covariate-adjusted linear regression models identified several significant microbiome associations with continuous stool metal/element concentrations. For instance, Zn was positively associated with Turicibacter sanguinis (coef = 1.354, q-value = 0.039) and negatively associated with Eubacterium eligens (coef = -0.794, q-value = 0.044). Higher concentrations of Cd were associated with lower Eubacterium eligens (coef = -0.774, q-value = 0.045). Additionally, a total of 490 significant functional pathways such as biosynthesis and degradation/utilization/assimilation were identified, corresponding to different functions, including amino acid synthesis and carbohydrate degradation. Our results suggest links among metal exposures, pediatric gut microbiome multiomics, and potential health implications. Future work will further explore their relation to childhood health.

The epigenome, the collection of all the epigenetic marks, is highly susceptible to environmental exposures. In this chapter, we provide an overview of the most studied epigenetic marks that may be affected by environmental toxicants. We review epigenomic effects of metals, air pollution, persistent organic pollutants (POPs), endocrine disruptors, and the exposome. We also discuss environmental epigenomics in the context of precision medicine and the potential of epigenomic changes as early biomarkers of environmentally related health disorders. We conclude by discussing recent developments in assessing past exposures using epigenome-wide scanning and evaluating age acceleration.