Triple Negative Breast Cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer, which is more frequently diagnosed in African American (AA) women than in European American (EA) women. The purpose of this study is to investigate the role of social determinants in racial disparities in TNBC. Data on Louisiana TNBC patients diagnosed in 2010–2012 were collected and geocoded to census tract of residence at diagnosis by the Louisiana Tumor Registry. Using multilevel statistical models, we analyzed the role of neighborhood concentrated disadvantage index (CDI), a robust measure of physical and social environment, in racial disparities in TNBC incidence, stage at diagnosis, and stage-specific survival for the study population. Controlling for age, we found that AA women had a 2.21 times the incidence of TNBC incidence compared to EA women. Interestingly, the incidence of TNBC was independent of neighborhood CDI and adjusting for neighborhood environment did not impact the observed racial disparity. AA women were more likely to be diagnosed at later stages and CDI was associated with more advanced stages of TNBC at diagnosis. CDI was also significantly associated with poorer stage-specific survival. Overall, our results suggest that neighborhood disadvantage contributes to racial disparities in stage at diagnosis and survival among TNBC patients, but not to disparities in incidence of the disease. Further research is needed to determine the mechanisms through which social determinants affect the promotion and progression of this disease and guide efforts to improve overall survival.
Hepatocellular carcinoma (HCC) is a male-dominated disease. Currently, gender differences remain incompletely defined. Data from the state tumor registry were used to investigate differences in demographics, comorbidities, treatment patterns, and cancer-specific survival (HSS) among HCC patients according to gender. Additional analyses were performed to evaluate racial differences among women with HCC. 2627 patients with HCC were included; 498 (19%) were women. Women were mostly white (58%) or African American (39%)—only 3.8% were of another or unknown race. Women were older (65.1 vs. 61.3 years), more obese (33.7% vs. 24.2%), and diagnosed at an earlier stage (31.7% vs. 28.4%) than men. Women had a lower incidence of liver associated comorbidities (36.1% vs. 43%), and more often underwent liver-directed surgery (LDS; 27.5% vs. 22%). When controlling for LDS, no survival differences were observed between genders. African American women had similar HSS rates compared to white women (HR 1.14 (0.91,1.41), p = 0.239) despite having different residential and treatment geographical distributions. African American race and age >65 were predictive for worse HSS in men, but not in women. Overall, women with HCC undergo more treatment options—likely because of the earlier stage of the cancer and/or less severe underlying liver disease. However, when controlling for similar stages and treatments, HCC treatment outcomes were similar between men and women. African American race did not appear to influence outcomes among women with HCC as it did in men.
Purpose: Currently, rural residents in the United States (US) experience a greater cancer burden for tobacco-related cancers and cancers that can be prevented by screening. We aim to characterize geographic determinants of colorectal cancer (CRC) incidence in Louisiana due to rural residence and other known geographic risk factors, area socioeconomic status (SES), and cultural region (Acadian or French-speaking). Methods: Primary colorectal cancer diagnosed among adults 30 years and older in 2008–2017 were obtained from the Louisiana Tumor Registry. Population and social and economic data were obtained from US Census American Community Survey. Rural areas were defined using US Department of Agriculture 2010 rural–urban commuting area codes. Estimates of relative risk (RR) were obtained from multilevel binomial regression models of incidence. Results: The study population was 16.1% rural, 18.4% low SES, and 17.9% Acadian. Risk of CRC was greater among rural white residents (RR Women: 1.09(1.02–1.16), RR Men: 1.11(1.04–1.18)). Low SES was associated with increased CRC for all demographic groups, with excess risk ranging from 8% in Black men (RR: 1.08(1.01–1.16)) to 16% in white men (RR: 1.16(1.08–1.24)). Increased risk in the Acadian region was greatest for Black men (RR: 1.21(1.10–1.33)) and women (RR: 1.21(1.09–1.33)). Rural–urban disparities in CRC were no longer significant after controlling for SES and Acadian region. Conclusion: SES remains a significant determinant of CRC disparities in Louisiana and may contribute to observed rural–urban disparities in the state. While the intersectionality of CRC risk factors is complex, we have confirmed a robust regional disparity for the Acadian region of Louisiana.
Potassium ions (K+) are critical electrolytes that regulate multiple functions in immune cells. Recent studies have shown that the elevated concentration of extracellular potassium in the tumor interstitial fluid limits T cell effector function and suppresses the anti-tumor capacity of tumor-associated macrophages (TAMs). The effect of excess potassium on the biology of myeloid-derived suppressor cells (MDSCs), another important immune cell component of the tumor microenvironment (TME), is unknown. Here, we present data showing that increased concentrations of potassium chloride (KCl), as the source of K+ ions, facilitate autophagy by increasing the expression of the autophagosome marker LC3β. Simultaneously, excess potassium ions significantly decrease the expression of arginase I (Arg I) and inducible nitric oxide synthase (iNOS) without reducing the ability of MDSCs to suppress T cell proliferation. Further investigation reveals that excess K+ ions decrease the expression of the transcription factor C/EBP-β and alter the expression of phosphorylated kinases. While excess K+ ions downregulated the expression levels of phospho-AMPKα (pAMPKα), it increased the levels of pAKT and pERK. Additionally, potassium increased mitochondrial respiration as measured by the oxygen consumption rate (OCR). Interestingly, all these alterations induced by K+ ions were abolished by the autophagy inhibitor 3-methyladenine (3-MA). Our results suggest that hyperosmotic stress caused by excess K+ ions regulate the mitochondrial respiration and signaling pathways in MDSCs to trigger the process of autophagy to support MDSCs’ immunosuppressive function by mechanisms independent of Arg I and iNOS. Overall, our in vitro and ex vivo findings offer valuable insights into the adaptations of MDSCs within the K+ ion-rich TME, which has important implications for MDSCs-targeted therapies.
Introduction: Medicaid expansion (ME) has positively impacted colon cancer screening. ME’s effect on colon cancer treatment is less clear. This study analyses the effect of ME on patterns of colon cancer treatment. Methods: Patients with primary invasive colon cancer were identified using the Louisiana Tumor Registry. Patients diagnosed with colon cancer prior to ME (2014–2015) were compared to those diagnosed after (2017–2018). Coordinate variables were analyzed using Fisher’s exact test. Treatment status was modeled with multivariable logistic regression and the results are reported as adjusted odds ratios. Results: The proportion of uninsured patients decreased following ME (5.5 versus 1.9, p < 0.001), with the greatest reductions among patients between 45 and 54 years old (13.5% to 3.5%, p < 0.0001), African Americans (8.9 to 2.1%, p < 0.0001), and those in high-poverty neighborhoods (7.1 to 2.1%, p < 0.0001). Following ME, all patients with Stage I-III disease were more likely to receive surgery (OR = 1.95; 95%: CI 1.21–3.14)—especially the extremely impoverished (OR = 2.39; 95% CI 1.41–4.02). Young patients with Stage IV colon cancer were more likely to receive chemotherapy (OR-1.6; 95% CI 1.03–2.4). Patients with Stage IV colon cancer were less likely to receive treatment within 30 days of diagnosis (OR = 0.7; 95% CI 0.5–0.9), but, on subset analysis, this was only observed in non-Medicaid patients. Conclusion: ME is associated with increased treatment for patients with colon cancer, and it did not appear to affect time to treatment. However, it seems to affect different subsets of the population differently.
Background: Disadvantaged neighborhood environments are a source of chronic stress which undermines optimal adolescent health. This study investigated relationships between the neighborhood social environment, specifically, chronic stress exposures, adiposity, and cardiometabolic disease risk factors among 288 Louisiana adolescents aged 10 to 16 years. Methods: This cross-sectional study utilized baseline data from the Translational Investigation of Growth and Everyday Routines in Kids (TIGER Kids) study. Adolescent data were obtained using self-reported questionnaires (demographics and perceived neighborhood disorder), anthropometry, body imaging, and a blood draw while objective neighborhood data for the concentrated disadvantage index were acquired from the 2016 American Community Survey five-year block group estimates, 2012–2016. Multilevel linear regression models were used to examine whether neighborhood concentrated disadvantage index and perceived neighborhood disorder were associated with body mass index, waist circumference, body fat, adipose tissue, blood pressure, and lipids. We performed multilevel logistic regression to determine the odds of elevated adiposity and cardiometabolic disease risk for adolescents living in neighborhoods with varying levels of neighborhood concentrated disadvantage and disorder. Results: Adolescents living in neighborhoods with higher disadvantage or disorder had greater waist circumference and total percent body fat compared to those in less disadvantaged and disordered neighborhoods (p for trend < 0.05). Neighborhood disadvantage was also positively associated with percentage of the 95th Body Mass Index percentile and visceral abdominal adipose tissue mass while greater perceived neighborhood disorder was related to higher trunk fat mass and diastolic blood pressure (p for trend < 0.05). Living in the most disadvantaged was associated with greater odds of obesity (OR: 2.9, 95% CI:1.3, 6.5) and being in the top tertile of body fat mass (OR: 3.0, 95% CI: 1.4, 6.6). Similar results were found with neighborhood disorder for odds of obesity (OR: 2.1, 95% CI:1.1, 4.2) and top tertile of body fat mass (OR: 2.1, 95% CI:1.04, 4.1). Conclusions: Neighborhood social environment measures of chronic stress exposure were associated with excess adiposity during adolescence, and relationships were most consistently identified among adolescents living in the most disadvantaged and disordered neighborhoods. Future studies should account for the influences of the neighborhood environment to stimulate equitable improvements in adolescent health. Clinical Trials Registration: # NCT02784509.