Project description:Background: Low socioeconomic status (SES) has been linked to chronic stress and poorer health outcomes for marginalized communities in the U.S. The biological processes mediating the impact of SES on health to promote chronic diseases, such as cancer, remain poorly understood. Here, we aim to determine how changes in DNA methylation are linked to neighborhood-level socioeconomic deprivation, thereby promoting cancer initiation and progression through cancer- and immune-related pathways. Methods: We extracted DNA from 402 fresh frozen tissues from 289 women in the NCI-Maryland Breast Cancer Cohort, including 185 tumor samples, 113 additional paired adjacent normal samples, and 104 normal tissues from reduction mammoplasty. Census-tract level socioeconomic deprivation was measured via a Neighborhood Deprivation Index (NDI) using the geocoded addresses from our study participants. DNA methylation values were acquired using the Illumina Infinium MethylationEPIC 850K Beadchip. We conducted a differentially methylated probe (DMP) analysis between tumor and adjacent normal tissue to characterize methylation profiles by NDI status. We also used methylCIBERSORT to estimate immune cell subpopulation differences by tissue type and NDI status. Results: NDI was significantly associated with self-reported race in our cohort in both normal (p<0.0001, 95% CI -4.32, -2.58) and tumor (p<0.0001, 95% CI -4.22, -2.79) tissue. Our DMP analysis showed more significant methylation events (hypo- or hyper- methylation of the tumor tissue compared to adjacent normal tissue) in the NDI high group compared to the NDI low group. We also identified five CpG sites that were significantly hypomethylated in the tumors of the NDI high group, including two tumor suppressor genes, LRIG1 (p=1.99 x10-10) and WWOX (p=6.47 x 10-9). These methylation changes translated to an inverse relationship between gene expression for these tumor suppressor genes and NDI. We also identified significantly lower neutrophils in the NDI high tumors compared to NDI low tumors (p=0.001, 95% CI -0.112, -0.028). Conclusions: Overall, our analysis provides evidence that high neighborhood deprivation can lead to pro-tumorigenic changes in DNA methylation and gene expression that may impact the immune microenvironment, breast cancer progression, and overall survival.

Project description:BackgroundDespite past and ongoing efforts to achieve health equity in the USA, racial and ethnic disparities persist and appear to be exacerbated by COVID-19.ObjectiveEvaluate neighborhood-level deprivation and English language proficiency effect on disproportionate outcomes seen in racial and ethnic minorities diagnosed with COVID-19.DesignRetrospective cohort study SETTING: Health records of 12 Midwest hospitals and 60 clinics in Minnesota between March 4, 2020, and August 19, 2020 PATIENTS: Polymerase chain reaction-positive COVID-19 patients EXPOSURES: Area Deprivation Index (ADI) and primary language MAIN MEASURES: The primary outcome was COVID-19 severity, using hospitalization within 45 days of diagnosis as a marker of severity. Logistic and competing-risk regression models assessed the effects of neighborhood-level deprivation (using the ADI) and primary language. Within race, effects of ADI and primary language were measured using logistic regression.ResultsA total of 5577 individuals infected with SARS-CoV-2 were included; 866 (n = 15.5%) were hospitalized within 45 days of diagnosis. Hospitalized patients were older (60.9 vs. 40.4 years, p < 0.001) and more likely to be male (n = 425 [49.1%] vs. 2049 [43.5%], p = 0.002). Of those requiring hospitalization, 43.9% (n = 381), 19.9% (n = 172), 18.6% (n = 161), and 11.8% (n = 102) were White, Black, Asian, and Hispanic, respectively. Independent of ADI, minority race/ethnicity was associated with COVID-19 severity: Hispanic patients (OR 3.8, 95% CI 2.72-5.30), Asians (OR 2.39, 95% CI 1.74-3.29), and Blacks (OR 1.50, 95% CI 1.15-1.94). ADI was not associated with hospitalization. Non-English-speaking (OR 1.91, 95% CI 1.51-2.43) significantly increased odds of hospital admission across and within minority groups.ConclusionsMinority populations have increased odds of severe COVID-19 independent of neighborhood deprivation, a commonly suspected driver of disparate outcomes. Non-English-speaking accounts for differences across and within minority populations. These results support the ongoing need to determine the mechanisms that contribute to disparities during COVID-19 while also highlighting the underappreciated role primary language plays in COVID-19 severity among minority groups.

Project description:Background: Low socioeconomic status (SES) has been linked to chronic stress and poorer health outcomes for marginalized communities in the U.S. The biological processes mediating the impact of SES on health to promote chronic diseases, such as cancer, remain poorly understood. Here, we aim to determine how changes in DNA methylation are linked to neighborhood-level socioeconomic deprivation, thereby promoting cancer initiation and progression through cancer- and immune-related pathways. Methods: We extracted DNA from 402 fresh frozen tissues from 289 women in the NCI-Maryland Breast Cancer Cohort, including 185 tumor samples, 113 additional paired adjacent normal samples, and 104 normal tissues from reduction mammoplasty. Census-tract level socioeconomic deprivation was measured via a Neighborhood Deprivation Index (NDI) using the geocoded addresses from our study participants. DNA methylation values were acquired using the Illumina Infinium MethylationEPIC 850K Beadchip. We conducted a differentially methylated probe (DMP) analysis between tumor and adjacent normal tissue to characterize methylation profiles by NDI status. We also used methylCIBERSORT to estimate immune cell subpopulation differences by tissue type and NDI status. Results: NDI was significantly associated with self-reported race in our cohort in both normal (p<0.0001, 95% CI -4.32, -2.58) and tumor (p<0.0001, 95% CI -4.22, -2.79) tissue. Our DMP analysis showed more significant methylation events (hypo- or hyper- methylation of the tumor tissue compared to adjacent normal tissue) in the NDI high group compared to the NDI low group. We also identified five CpG sites that were significantly hypomethylated in the tumors of the NDI high group, including two tumor suppressor genes, LRIG1 (p=1.99 x10-10) and WWOX (p=6.47 x 10-9). These methylation changes translated to an inverse relationship between gene expression for these tumor suppressor genes and NDI. We also identified significantly lower neutrophils in the NDI high tumors compared to NDI low tumors (p=0.001, 95% CI -0.112, -0.028). Conclusions: Overall, our analysis provides evidence that high neighborhood deprivation can lead to pro-tumorigenic changes in DNA methylation and gene expression that may impact the immune microenvironment, breast cancer progression, and overall survival.

Project description:BackgroundPeople who use drugs (PWUD) are known to fear calling emergency medical services (EMS) for drug overdoses. In response, drug-related Good Samaritan Laws (GSLs) have been widely adopted in the USA and Canada to encourage bystanders to call emergency medical services (EMS) in the event of a drug overdose. However, the effect of GSLs on EMS-calling behaviours has been understudied. We sought to identify factors associated with EMS-calling, including the enactment of the Canadian GSL in May 2017, among PWUD in Vancouver, Canada, a setting with an ongoing overdose crisis.MethodsData were derived from three prospective cohort studies of PWUD in Vancouver in 2014-2018. Multivariable logistic regression was used to determine factors associated with EMS-calling among PWUD who witnessed an overdose event. An interrupted time series (ITS) analysis was employed to assess the impact of GSL on monthly prevalence of EMS-calling.ResultsAmong 540 eligible participants, 321 (59%) were males and 284 (53%) reported calling EMS. In multivariable analysis, ever having administered naloxone three or more times (adjusted odds ratio [AOR] 2.00; 95% confidence interval [CI] 1.08-3.74) and residence in the Downtown Eastside (DTES) neighbourhood of Vancouver (AOR 1.96; 95% CI 1.23-3.13) were positively associated with EMS-calling, while living in a single occupancy hotel (SRO) was negatively associated with EMS-calling (AOR 0.51; 95% CI 0.30-0.86). The post-GSL enactment period was not associated with EMS-calling (AOR 0.81; 95% CI 0.52-1.25). The ITS found no significant difference in the monthly prevalence of EMS-calling between pre- and post-GSL enactment periods.ConclusionWe observed EMS being called about half the time and the GSL did not appear to encourage EMS-calling. We also found that individuals living in SROs were less likely to call EMS, which raises concern given that fatal overdose cases are concentrated in SROs in our setting. The link between many naloxone administrations and EMS-calling could indicate that those with prior experience in responding to overdose events were more willing to call EMS. Increased efforts are warranted to ensure effective emergency responses for drug overdoses among PWUD.

Dataset Information

Geospatial Variations and Neighborhood Deprivation in Drug-Related Admissions and Overdoses.

Publications

Geospatial Variations and Neighborhood Deprivation in Drug-Related Admissions and Overdoses.

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