Rebecca D. Kehm

BackgroundPhthalates are ubiquitous endocrine-disrupting chemicals with near-universal exposure during pregnancy. Phthalate molecular weight class may differentially influence endocrine-sensitive developmental processes, including mammary development. Yet no studies have examined prenatal phthalate exposure in relation to adolescent breast tissue composition (BTC).ObjectiveWe examined associations between prenatal, third-trimester urinary concentrations of nine phthalate metabolites (three low–molecular-weight [LMW] and six high–molecular-weight [HMW]) and adolescent BTC among 127 girls from a New York City birth cohort.MethodsWe used optical spectroscopy to quantify BTC (water, lipid, collagen, total hemoglobin) and a composite optical index (OI), with all outcomes standardized to a mean of 0 and standard deviation of 1. We fit multivariable linear regression models adjusted for age at measurement, percent body fat, maternal pre-pregnancy body mass index (BMI), and socioeconomic status, and applied false discovery rate (FDR) correction across metabolite–outcome tests. We also used Bayesian kernel machine regression (BKMR) to explore joint mixture effects.ResultsPrenatal mono-2-ethylhexyl phthalate (MEHP) concentrations were associated with higher percent water content (β = 0.17, 95% CI: 0.01, 0.33), lower percent lipid content (β = −0.17, 95% CI: −0.33, −0.01), and higher optical index (OI) (β = 0.19, 95% CI: 0.02, 0.35) in adjusted models. However, none of these associations remained statistically significant after correction for multiple comparisons using the FDR. Other HMW metabolites showed smaller, imprecise estimates, while LMW metabolites were not consistently associated with BTC measures. BKMR findings were directionally concordant but did not indicate a strong overall mixture effect.SignificanceIf replicated, these findings suggest that higher prenatal concentrations of the HMW phthalate metabolite MEHP may influence breast tissue development during a sensitive window of susceptibility, and are consistent with greater fibroglandular tissue composition, a phenotype linked to higher mammographic density.

Background:Liver cancer incidence and mortality are rising in the United States, with marked racial and socioeconomic disparities. Persistent poverty, defined as communities in which ≥20% of residents have lived below the federal poverty line for ≥30 years, is an important but understudied contextual determinant of cancer survival. This study examined the association between census tract–level persistent poverty and liver cancer survival.Methods:We analyzed 73,695 adult, population-based patients with liver cancer ages ≥20 years, diagnosed between 2006 and 2019 in the Surveillance, Epidemiology, and End Results 17 Registries. Persistent poverty status was assigned by residence at diagnosis. Cancer-specific and overall survival were estimated using Kaplan–Meier and Cox models, adjusting for demographic factors, stage at diagnosis, and initial treatment. We evaluated effect modification by age, sex, race/ethnicity, rurality, and stage at diagnosis.Results:Over 168,715 person-years, 56,373 deaths occurred, of which 81% were cancer-specific. Eleven percent of patients lived in persistent poverty tracts. The median cancer-specific survival was 16 months in persistent poverty tracts versus 22 months in nonpersistent tracts (P < 0.001). In fully adjusted models, persistent poverty was associated with 9% higher cancer-specific mortality (HR = 1.09; 95% CI, 1.06–1.12) and 11% higher all-cause mortality (HR = 1.11; 95% CI, 1.09–1.14). Associations were strongest in patients <65 years and with localized disease, with no significant differences by race/ethnicity, sex, or rurality.Conclusions:Living in a persistent poverty census tract is associated with worse liver cancer survival, particularly among younger patients and those with localized disease.Impact:Interventions and policies targeting economically disadvantaged communities may be important for reducing liver cancer survival disparities.

Supplementary Table S1. Association between residence in a persistent poverty census tract and mortality risk, stratified by different follow-up times, among liver cancer patients diagnosed from 2006 to 2019 in the SEER17 Registries, n = 73,695

Introduction: The incidence of carcinomas among adolescents and young adults (AYAs; ages 15–39) is rising. However, most research treats AYAs as a single group, potentially obscuring important age‐ and sex‐specific trends. This study examined long‐term trends in carcinoma incidence among AYAs in the U.S., overall and by 5 year age groups. Methods: We conducted a population‐based, retrospective time‐series analysis using data from eight U.S. cancer registries in the Surveillance, Epidemiology and End Results database. The study included 128,255 AYAs diagnosed with malignant carcinoma between 1975–2021. Average annual percent change (AAPC) in incidence rates was estimated using Joinpoint regression, stratified by age, sex, and carcinoma subtype. Results: A total of 128,255 individuals, aged 15–39, who were diagnosed with carcinoma between 1975–2021; 77.5% of AYA carcinoma cases occurred in females. The overall incidence of carcinomas increased by 0.61% (CI: 0.43–0.80) per year in AYAs from 1975 to 2021, with similar increases observed in females (AAPC: 0.68%; 95% CI, 0.50–0.87) and males (AAPC: 0.71%; 95% CI, 0.45–0.97). When stratified by age group, overall carcinoma incidence increased in each 5‐year group; the largest relative increase was in those aged 15–19 (AAPC: 1.66%; 95% CI, 0.71–2.62) and the smallest was in those aged 35–39 (AAPC: 0.48%; 95% CI, 0.22–0.74). Conclusions: Carcinoma incidence is increasing in the AYA population within each 5‐year age group, including among adolescents, a group in which these cancers have historically been rare. These findings highlight the urgent need to investigate the causes of this increase to guide targeted prevention and early detection efforts.

Background: Liver cancer incidence and mortality are rising in the United States, with marked racial and socioeconomic disparities. Persistent poverty, defined as communities in which ≥20% of residents have lived below the federal poverty line for ≥30 years, is an important but understudied contextual determinant of cancer survival. This study examined the association between census tract–level persistent poverty and liver cancer survival. Methods: We analyzed 73,695 adult, population-based patients with liver cancer ages ≥20 years, diagnosed between 2006 and 2019 in the Surveillance, Epidemiology, and End Results 17 Registries. Persistent poverty status was assigned by residence at diagnosis. Cancer-specific and overall survival were estimated using Kaplan–Meier and Cox models, adjusting for demographic factors, stage at diagnosis, and initial treatment. We evaluated effect modification by age, sex, race/ethnicity, rurality, and stage at diagnosis. Results: Over 168,715 person-years, 56,373 deaths occurred, of which 81% were cancer-specific. Eleven percent of patients lived in persistent poverty tracts. The median cancer-specific survival was 16 months in persistent poverty tracts versus 22 months in nonpersistent tracts (P < 0.001). In fully adjusted models, persistent poverty was associated with 9% higher cancer-specific mortality (HR = 1.09; 95% CI, 1.06–1.12) and 11% higher all-cause mortality (HR = 1.11; 95% CI, 1.09–1.14). Associations were strongest in patients <65 years and with localized disease, with no significant differences by race/ethnicity, sex, or rurality. Conclusions: Living in a persistent poverty census tract is associated with worse liver cancer survival, particularly among younger patients and those with localized disease. Impact: Interventions and policies targeting economically disadvantaged communities may be important for reducing liver cancer survival disparities.

Evidence suggests that recreational physical activity (RPA) during adolescence is associated with lower breast cancer (BC) risk, but the biological mechani

The impact of physical health conditions on coronavirus disease of 2019 (COVID-19) severity in World Trade Center disaster-exposed populations remains understudied. We examined the association of type, number and diagnosis time of pre-existing health conditions with COVID-19 severity, using the WTC Health Registry (WTCHR). We analyzed 3568 WTCHR enrollees with self-reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in a 2021 follow-up survey. COVID-19 severity was measured by self-reported symptom duration (4 weeks) and hospitalization (hospitalized versus not). Pre-existing gastroesophageal reflux disease (GERD), respiratory conditions, cardiovascular conditions, and diabetes were self-reported and categorized into four groups (no diagnosis, post-9/11, pre-9/11, and undefinable). We used multinomial logistic regression and binary logistic regression to analyze the association of comorbidities with COVID-19 symptom duration and hospitalization, respectively, adjusting for post-traumatic stress disorder and demographic factors. Analysis was also conducted separately by enrollee type: rescue and recovery workers (RRW) vs. community members (non-RRW). Having all four health conditions post-9/11 was associated with longer symptom duration after SARS-CoV-2 infection (>4 weeks) among RRW (AOR: 2.66, 95% CI: 1.03–6.87). Reporting a post-9/11 respiratory condition was associated with an increased risk of being hospitalized among RRW and an increased risk of longer symptom duration (>4 weeks) among non-RRW. While post-9/11 diabetes was associated with an increased risk of longer symptom duration among RRW, post-9/11 GERD and pre-9/11 cardiovascular conditions were associated with an increased risk of longer symptom duration and being hospitalized among non-RRW, respectively. The impact of certain health conditions on COVID-19 severity varied across enrollee types and time of diagnosis. Given the lasting health impacts of 9/11-related exposures, targeted medical surveillance and proactive healthcare interventions are critical for mitigating the risk of severe COVID-19 illness in this population.

Background: Understanding social drivers of mammography screening is critical to implementing breast cancer screening guidelines that maximize benefits and minimize harms across diverse populations. We examined racial/ethnic, socioeconomic, and geographic patterns in guideline-discordant underscreening and overscreening according to guidelines based on age and mortality risk. Methods: We used 2022 Behavioral Risk Factor Surveillance System data and major screening guidelines to define screening participation. Underscreening captured mammography in the past 2 years among women ages 50 to 74 years. Overscreening included any mammography beyond age 74 years or among women ages 50+ years with high mortality risk. We used modified Poisson regression to examine screening by race/ethnicity, regular healthcare provider access, and metropolitan, educational, and marital status. Results: Among 88,326 women ages 50 to 74 years, compared with non-Hispanic (NH) White, NH American Indian/Alaskan Native [adjusted prevalence ratio (aPR) = 0.88, 95% confidence interval (CI), 0.79–0.97] and NH women of unknown race (aPR = 0.86, 95% CI, 0.78–0.94) were less likely to be screened, whereas NH Black (aPR = 1.11, 95% CI, 1.09–1.13) women were more likely. Among 31,477 women ages 75+ years, NH Black women were more likely to be screened than NH White women (aPR = 1.07, 95% CI, 1.01–1.14). Among women with high mortality risk, NH Black (aPR = 1.20, 95% CI, 1.12–1.28) women were more likely to be screened than NH White women. Screening was lower among women with more limited socioeconomic resources regardless of age or mortality risk. Conclusions: Findings reveal social drivers of underscreening and overscreening and the need for equitable breast cancer screening delivery. Impact: This work calls for strengthening implementation and de-implementation efforts to optimize breast cancer screening.