Reciprocal Effect of Environmental Stimuli to Regulate the Adipogenesis and Osteogenesis Fate Decision in Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs).

Mesenchymal stem cells derived from bone marrow (BM-MSCs) can differentiate into adipocytes and osteoblasts. Various external stimuli, including environmental contaminants, heavy metals, dietary, and physical factors, are shown to influence the fate decision of BM-MSCs toward adipogenesis or osteogenesis. The balance of osteogenesis and adipogenesis is critical for the maintenance of bone homeostasis, and the interruption of BM-MSCs lineage commitment is associated with human health issues, such as fracture, osteoporosis, osteopenia, and osteonecrosis. This review focuses on how external stimuli shift the fate of BM-MSCs towards adipogenesis or osteogenesis. Future studies are needed to understand the impact of these external stimuli on bone health and elucidate the underlying mechanisms of BM-MSCs differentiation. This knowledge will inform efforts to prevent bone-related diseases and develop therapeutic approaches to treat bone disorders associated with various pathological conditions.

The 2023 GOLD Report: Updated Guidelines for Inhaled Pharmacological Therapy in Patients with Stable COPD.

Over the past 22 years, annual GOLD Reports have documented important changes in guidance and recommendations for uniformly treating patients with chronic obstructive pulmonary disease (COPD) with the goal of improving outcomes in patients suffering from this condition. The most recent GOLD Report, released in 2023, shows continued refinement in several areas, including more precise definitions of COPD and exacerbations of COPD, a new set of parameters to assess exacerbation severity, an updated COPD assessment tool, updated guidelines for initial and follow-up treatment, new information regarding the association between pharmacological triple therapy and reduction in mortality, and new discussions of inhaler device choice and adherence to COPD medications. Whereas we do not address all of the new or updated material in GOLD's 2023 Report, we summarize key changes in GOLD's recommendations regarding inhalation therapy for stable COPD and frame these changes in the context of previous GOLD recommendations.

The association of preexisting severe asthma with COVID-19 outcomes.

PURPOSE OF REVIEW: Three years after the emergence of coronavirus disease 2019 (COVID-19), many studies have examined the association between asthma and COVID-related morbidity and mortality, with most showing that asthma does not increase risk. However, the U.S. Centers for Disease Control (CDC) currently suggests that patients with severe asthma may, nonetheless, be particularly vulnerable to COVID-19-related morbidity. RECENT FINDINGS: With respect to poor COVID-19 outcomes, our search yielded nine studies that quantified associations with severe asthma, seven that considered use of monoclonal antibodies (mAB), and 14 that considered inhaled corticosteroids (ICS) use. mAb and ICS use have been used as measures of severe asthma in several studies. Severe asthma was significantly associated with poor COVID-19 outcomes. The results for mAb and ICS were mixed. SUMMARY: An increased risk of poor COVID-19 outcomes in patients with severe asthma is possible. However, these studies remain sparse and suffer from several methodological limitations that hinder their interpretation. Additional evidence is needed to provide clear, cogent guidance for health agencies seeking to inform patients with asthma about potential risks due to COVID-19.

Impact of Paraben Exposure on Adiposity-Related Measures: An Updated Literature Review of Population-Based Studies.

Parabens are alkyl esters of p-hydroxybenzoic acid that are commonly used in pharmaceutical and cosmetic products. Humans are exposed to parabens when they use these products and through diet. There are growing concerns that paraben exposure can adversely impact human health. The endocrine-disrupting and obesogenic properties of parabens have been observed in animal studies and in vitro, prompting the increase in population-based studies of paraben exposure and adiposity-related endpoints. In this review, we summarize epidemiological studies published between 2017 and 2022 that examined paraben exposure in utero, between birth and adolescence, and in adulthood, in relation to adiposity-related measures. Overall, these studies provide some evidence that suggests that paraben exposure, especially during critical development windows, is associated with adiposity-related measures. However, we have noted several limitations in these studies, including the predominance of cross-sectional studies, inconsistent sample collection procedures, and small sample sizes, which should be addressed in future studies.

Interaction effect between overweight/obesity and alcohol consumption on hypertension risk in China: a longitudinal study.

OBJECTIVE: To explore the interaction effect between overweight/obesity and alcohol consumption on hypertension risk. DESIGN: A longitudinal study of the independent and combined effects of hypertension risk factors. SETTING: Twelve provinces in China, including Beijing Liaoning, Heilongjiang, Shanghai, Jiangsu, Shandong, Henan, Hubei, Hunan, Guangxi, Guizhou and Chongqing. PARTICIPANTS: Longitudinal data of China Health and Nutrition Survey, collected between 2011 and 2015, were used in this study. A total of 13 121 residents from 12 provinces were included and completed physical examinations and questionnaires at baseline. OUTCOME: First incidence of hypertension. RESULTS: Over a mean follow-up of 4 years, 690 incident hypertension cases were reported. After adjusting for age, gender, education level, marital status, physical activity, diabetes and smoking, high body mass index (BMI) and light drinking (OR=5.07, 95% CI 3.06 to 8.41), high waist circumference (WC) and light drinking (OR=4.81, 95% CI 2.92 to 7.91), high waist hip ratio and light drinking (OR=2.85, 95% CI 1.84 to 4.42) were the highest risk of all participants in the three combinations. Multiplicative interaction measures were statistically significant in overweight/obesity and drinking/light drinking/heavy drinking categories in men (p<0.05). Additive interactions were observed between high BMI and drinking in men (relative excess risk due to interaction=1.75, 95% CI 0.85 to 2.65, attributable proportion due to interaction=0.56, 95% CI 0.36 to 0.76, synergy index=6.43, 95% CI 1.02 to 28.84). CONCLUSIONS: Measures of body weight and size, particularly BMI and WC, appear to interact synergistically with alcohol consumption to increase the risk of hypertension in the Chinese population. Given that approximately 245 million people in China have hypertension, and that hypertension is a major cause of cardiovascular disease worldwide, our results may have implications for chronic disease prevention.

Racial Differences in the Tumor Immune Landscape and Survival of Women with High-Grade Serous Ovarian Carcinoma.

BACKGROUND: Tumor-infiltrating lymphocytes (TIL) confer a survival benefit among patients with ovarian cancer; however, little work has been conducted in racially diverse cohorts. METHODS: The current study investigated racial differences in the tumor immune landscape and survival of age- and stage-matched non-Hispanic Black and non-Hispanic White women with high-grade serous ovarian carcinoma (HGSOC) enrolled in two population-based studies (n = 121 in each racial group). We measured TILs (CD3+), cytotoxic T cells (CD3+CD8+), regulatory T cells (CD3+FoxP3+), myeloid cells (CD11b+), and neutrophils (CD11b+CD15+) via multiplex immunofluorescence. Multivariable Cox proportional hazard regression was used to estimate the association between immune cell abundance and survival overall and by race. RESULTS: Overall, higher levels of TILs, cytotoxic T cells, myeloid cells, and neutrophils were associated with better survival in the intratumoral and peritumoral region, irrespective of tissue compartment (tumor, stroma). Improved survival was noted for T-regulatory cells in the peritumoral region and in the stroma of the intratumoral region, but no association for intratumoral T-regulatory cells. Despite similar abundance of immune cells across racial groups, associations with survival among non-Hispanic White women were consistent with the overall findings, but among non-Hispanic Black women, most associations were attenuated and not statistically significant. CONCLUSIONS: Our results add to the existing evidence that a robust immune infiltrate confers a survival advantage among women with HGSOC; however, non-Hispanic Black women may not experience the same survival benefit as non-Hispanic White women with HGSOC. IMPACT: This study contributes to our understanding of the immunoepidemiology of HGSOC in diverse populations.

Psychosocial factors associated with genetic testing status among African American women with ovarian cancer: Results from the African American Cancer Epidemiology Study.

BACKGROUND: Racial disparities in the uptake of cancer genetic services are well documented among African American (AA) women. Understanding the multiple social and psychological factors that can influence the uptake of genetic testing among AA women is needed. METHODS: Data came from 270 AA women diagnosed with ovarian cancer and participating in a population-based, case-control study of ovarian cancer who were asked about genetic testing. Logistic regression analyses tested the associations of predisposing, enabling, and need factors with reported genetic testing uptake. RESULTS: One-third of the sample (35%) reported having had genetic testing. In the multivariable model, AA women with higher incomes had more than double the odds of being tested than those with the lowest income (odds ratio [OR] for $25,000-$74,999, 2.04; 95% confidence interval [CI], 1.06-3.99; OR for ≥$75,000, 2.32; 95% CI, 0.92-5.94). AA women who reported employment discrimination were significantly less likely to report genetic testing than those who did not report job discrimination (OR, 0.39; 95% CI, 0.14-0.95). Marital status, Medicaid versus other insurance, prayer frequency, and perceived social support were significantly associated with genetic testing uptake in bivariate analyses but were not significant contributors in multivariable analyses. CONCLUSIONS: Consistent with other studies of AA women, a minority of African American Cancer Epidemiology Study participants had undergone genetic testing. Having a lower income and experiencing job discrimination decreased the likelihood of testing. These results provide foundational evidence supporting the need for interventions to improve the uptake of genetic testing among AA women by reducing cost barriers and providing credible assurances that genetic results will be kept private and not affect social factors such as employability.

Asthma in Adult Patients with COVID-19. Prevalence and Risk of Severe Disease.

Rationale: Health outcomes of people with coronavirus disease (COVID-19) range from no symptoms to severe illness and death. Asthma, a common chronic lung disease, has been considered likely to increase the severity of COVID-19, although data addressing this hypothesis have been scarce until very recently.Objectives: To review the epidemiologic literature related to asthma's potential role in COVID-19 severity.Methods: Studies were identified through the PubMed (MEDLINE) and medRxiv (preprint) databases using the search terms "asthma," "SARS-CoV-2" (severe acute respiratory syndrome coronavirus 2), and "COVID-19," and by cross-referencing citations in identified studies that were available in print or online before December 22, 2020.Measurements and Main Results: Asthma prevalence data were obtained from studies of people with COVID-19 and regional health statistics. We identified 150 studies worldwide that allowed us to compare the prevalence of asthma in patients with COVID-19 by region, disease severity, and mortality. The results of our analyses do not provide clear evidence of increased risk of COVID-19 diagnosis, hospitalization, severity, or mortality due to asthma.Conclusions: These findings could provide some reassurance to people with asthma regarding its potential to increase their risk of severe morbidity from COVID-19.

Maintenance Therapy with Nebulizers in Patients with Stable COPD: Need for Reevaluation.

Patients with stable COPD rely heavily on inhaled bronchodilators and corticosteroids to control symptoms, maximize quality of life, and avoid exacerbations and costly hospitalizations. These drugs are typically delivered by hand-held inhalers or nebulizers. The majority of patients are prescribed inhalers due to their perceived convenience, portability, and lower cost, relative to nebulizers. Unfortunately, poor inhaler technique compromises symptom relief in most of these patients. In contrast to one or two puffs through an inhaler, nebulizers deliver a drug over many breaths, through tidal breathing, and hence are more forgiving to poor inhalation technique. To what extent susceptibility to errors in their use may influence the relative effectiveness of these two types of inhalation device has received little attention in COPD research. In 2005, a systematic review of the literature concluded that nebulizers and inhalers are equally effective in patients who are adequately trained to use their inhalation device. This conclusion was based on two small clinical trials that only examined objective measures of lung function. Since then, additional studies have found that maintenance therapy administered by nebulizers could improve patients' reported feelings of symptom relief, quality of life, and satisfaction with treatment, compared to therapy administered by inhalers. Because it has been 15 years since the publication of the systematic review, in this article we summarize the results of studies that compared the effectiveness of inhalers with that of nebulizers in patients with stable COPD and discuss their implications for clinical practice and need for future research.

Cardiometabolic comorbidities and epithelial ovarian cancer risk among African-American women in the African-American Cancer Epidemiology Study (AACES).

BACKGROUND: Studies that have examined the association between cardiovascular comorbidities and epithelial ovarian cancer (EOC) have yielded inconsistent results. It remains unknown whether cardiometabolic disease is associated with EOC in African American (AA) women, who have a higher prevalence of cardiovascular disease and lower risk of EOC than White women. Here, we estimate the effect of cardiovascular comorbid conditions and EOC risk among AA women. METHODS: Data were available from 593 ovarian carcinoma patients and 752 controls enrolled in the African American Cancer Epidemiology Study (AACES). Participants were asked to self-report a history of hypertension, hyperlipidemia, and diabetes and any current medication use. The relationship between hypertension, hyperlipidemia, diabetes, and medications taken for these conditions was determined using multivariate logistic regression. RESULTS: Hypertension was associated with an increased risk (adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.01, 1.73), whereas diabetes and hyperlipidemia were associated with a decreased risk (aOR = 0.67, 95% CI = 0.49, 0.91 and aOR = 0.61, 95% CI = 0.47, 0.80, respectively) of EOC. Use of anti-diabetic medication was inversely associated with EOC risk, as was use of lipid lowering medications (in the overall study population), which were predominantly statins. Among women with hypertension, use of anti-hypertensive medications was inversely associated with EOC risk, with associations that were most pronounced for diuretics, ARBs and ACE inhibitors. CONCLUSION: Hypertension was associated with an increased EOC risk in this patient population, whereas an inverse association was observed for diabetes and hyperlipidemia. The decreased risk of EOC identified with use of anti-hypertensive, anti-diabetes or lipid-lowering medications could have implications for risk reduction strategies.

Inhalation Therapy for Stable COPD: 20 Years of GOLD Reports.

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) was formed in the late 1990s to spread awareness of chronic obstructive pulmonary disease (COPD) as a major public health problem and facilitate its prevention and treatment. GOLD has since become internationally recognized for the development of evidence-based strategy documents, most notably the annual GOLD Reports, for COPD diagnosis, management, and prevention. The GOLD Reports incorporate the latest evidence and expert consensus to guide the management and prevention of COPD on a global level. Since the first GOLD Report in 2001, profound innovations have taken place regarding inhaler device options, available pharmaceuticals, knowledge regarding effective dosages and potential side effects, and the various combinations of drugs used to relieve symptoms. Concomitantly, an evolution of expert opinion on how best to apply these innovations to the care of patients with COPD has also taken place, an evolution that is nowhere more detailed or definitive than in the 20 years of annual GOLD Reports. We summarize key features and trends in inhalation therapy for stable COPD in these Reports.

Association between interleukin-21 gene rs907715 polymorphism and gastric precancerous lesions in a Chinese population.

BACKGROUND: The single nucleotide polymorphisms of interleukin-21 (IL-21) gene were confirmed to be related to various diseases, but no studies have examined the possible role of IL-21 single nucleotide polymorphisms (SNPs) (rs907715, rs2221903, and rs12508721) in gastric precancerous lesions. AIM: To explore the associations between SNPs of IL-21 gene (rs907715, rs2221903, and rs12508721) and gastric precancerous lesions in a Chinese population. METHODS: Three SNPs of IL-21 were genotyped using polymerase chain reaction-ligase detection reaction in 588 cases and 290 healthy controls from May 2013 to December 2016 in northwestern China. Gastric precancerous lesions were confirmed by endoscopic examination and categorized as non-atrophic gastritis, atrophic gastritis, and intestinal metaplasia. Descriptive statistic and logistic regression were used for data analyses. RESULTS: IL-21 rs907715 genotype CC and C frequencies were higher in in patients with gastric precancerous lesions than in the controls (OR = 1.59, 95%CI: 1.06-2.38, P = 0.013; OR = 1.28, 95%CI: 1.01-2.22, P = 0.044, respectively) after adjusting for confounding factors. For SNP rs907715 in intestinal metaplasia patients, significant differences between cases and controls were observed in the frequencies of genotype CC and C (OR = 1.92, 95%CI: 1.24-2.98, P = 0.004; OR = 1.53, 95%CI: 1.04-2.24, P = 0.028, respectively); for non-atrophic gastritis and atrophic gastritis patients, the CC and C genotypes showed no significant association with risk in all models. No association between either rs2221903 or rs12508721 and gastric precancerous lesions was found in the present study. In the haplotype analysis, the TC haplotype (rs907715 and rs12508721) and TT haplotype (rs2221903 and rs907715) were more frequent in the case group than control group (P < 0.05). CONCLUSION: Our findings indicate that SNP rs907715 of IL-21 gene is associated with gastric precancerous lesions. The TC haplotype (rs907715 and rs12508721) and TT haplotype (rs2221903 and rs907715) increased the risk of gastric precancerous lesions. If confirmed, these findings will shed light on the etiology of precancerous lesions.

Association of XPG rs2094258 polymorphism with gastric cancer prognosis.

BACKGROUND: The xeroderma pigmentosum group G (XPG) gene at chromosome 13q33 consists of 15 exons, which may be related to the occurrence and development of gastric cancer (GC). AIM: To examine the association of several common single nucleotide polymorphisms (SNPs) of the XPG gene with GC risk and survival. METHODS: Five SNPs of XPG (rs2094258, rs751402, rs873601, rs2296147, and rs1047768) were genotyped by PCR restriction fragment length polymorphism in 956 histologically confirmed GC cases and 1012 controls in North China. GC patients were followed for survival status and, if deceased, cause of death. Logistic regression and Cox regression were used for analysing associations of XPG SNPs with risk of GC and prognosis, respectively. For rs2094258, heterozygous model (CT vs CC), homozygous model (TT vs CC), recessive model (TT vs CT + CC), and dominant model (TT + CT vs CC) were analyzed. RESULTS: None of the examined loci were statistically associated with GC risk, although rs2296147 was marginally associated with GC risk (P = 0.050). GC patients with the rs2094258 CT + CC genotype showed worse survival than those with the TT genotype (log-rank test, P = 0.028), and patients with the CC genotype had a tendency of unfavourable prognosis compared with those with the TT + CT genotype (log-rank test, P = 0.039). The increase in C alleles of rs2094258 [hazard ratio (HR) = 1.19, 95% confidence interval (CI): 1.02-1.45, P = 0.037] were associated with the long-term survival of GC cases. Other risk factors for survival included tumor differentiation (HR = 4.51, 95%CI: 1.99-8.23, P < 0.001), lymphovascular invasion (HR = 1.97, 95%CI: 1.44-3.01, P < 0.001), and use of chemotherapy (HR = 0.81, 95%CI: 0.63-0.98, P = 0.041). CONCLUSION: The XPG rs2094258 polymorphism may be associated with overall survival in GC patients.

Perceived discrimination, trust in physicians, and prolonged symptom duration before ovarian cancer diagnosis in the African American Cancer Epidemiology Study.

BACKGROUND: Discrimination and trust are known barriers to accessing health care. Despite well-documented racial disparities in the ovarian cancer care continuum, the role of these barriers has not been examined. This study evaluated the association of everyday discrimination and trust in physicians with a prolonged interval between symptom onset and ovarian cancer diagnosis (hereafter referred to as prolonged symptom duration). METHODS: Subjects included cases enrolled in the African American Cancer Epidemiology Study, a multisite case-control study of epithelial ovarian cancer among black women. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations of everyday discrimination and trust in physicians with a prolonged symptom duration (1 or more symptoms lasting longer than the median symptom-specific duration), and it controlled for access-to-care covariates and potential confounders. RESULTS: Among the 486 cases in this analysis, 302 women had prolonged symptom duration. In the fully adjusted model, a 1-unit increase in the frequency of everyday discrimination increased the odds of prolonged symptom duration 74% (OR, 1.74; 95% CI, 1.22-2.49), but trust in physicians was not associated with prolonged symptom duration (OR, 0.86; 95% CI, 0.66-1.11). CONCLUSIONS: Perceived everyday discrimination was associated with prolonged symptom duration, whereas more commonly evaluated determinants of access to care and trust in physicians were not. These results suggest that more research on the effects of interpersonal barriers affecting ovarian cancer care is warranted.

Dietary supplementation with Zyflamend poly-herbal extracts and fish oil inhibits intimal hyperplasia development following vascular intervention.

The polyherbal blend Zyflamend™ has been shown to have anti-inflammatory properties and attenuate inflammatory-modulated pathologies. Fish oils have also been shown to have cardioprotective properties. However, the beneficial effects of their combination have not been investigated. Intimal hyperplasia (IH), a pathological remodeling response of a vessel to injury, is heavily regulated by an immune-mediated reaction. The objective of this study was to determine if dietary supplementation with Zyflamend and/or Wholemega could affect inflammatory-dependent vascular remodeling mechanisms when provided at human equivalent doses. Based on their anti-inflammatory properties and protective benefits demonstrated in previous pre-clinical studies, we hypothesized administration of these supplements would prevent IH in an animal model of vascular injury. The diets of aged male rats were supplemented with human equivalent doses of Zyflamend (Zyf) and/or Wholemega (WMega) or placebo (Plac) for 1wk prior to balloon angioplasty (BA)-induced injury of the left carotid artery. At 28d post-injury morphometric analysis of carotid tissue revealed IH was decreased in Zyf + WMega animals compared to placebo, while Zyf or WMega independently had no significant effect. Serum cytokine screening indicated injury-induced interleukin family isoforms, interferon-γ, and macrophage inflammatory proteins were downregulated by Zyf + WMega. Immunohistochemical staining for monocyte/macrophage phenotypic markers revealed that while overall monocyte/macrophage vessel infiltration was not affected, Zyf + WMega limited the alternative differentiation of M2 macrophages and reduced the presence of myofibroblasts in the injured vessel wall. In summary, dietary supplementation with Zyf + WMega attenuated the acute inflammatory response following vascular injury and inhibited IH development in vivo.

Prediagnostic Proinflammatory Dietary Potential Is Associated with All-Cause Mortality among African-American Women with High-Grade Serous Ovarian Carcinoma.

BACKGROUND: Chronic inflammation is associated with ovarian carcinogenesis; yet, the impact of inflammatory-related exposures on outcomes has been understudied. OBJECTIVE: Given the poor survival of women diagnosed with ovarian cancer, especially African-Americans, we examined whether diet-associated inflammation, a modifiable source of chronic systemic inflammation measured by the dietary inflammatory index (DII), was associated with all-cause mortality among African-American women with ovarian carcinoma. METHODS: Data were available from 490 ovarian carcinoma patients enrolled in a population-based case-control study of African-American women with ovarian cancer, the African-American Cancer Epidemiology Study. Energy-adjusted DII (E-DII) scores were calculated based on prediagnostic dietary intake of foods alone or foods and supplements, which was self-reported using the 2005 Block Food Frequency Questionnaire. Cox proportional hazards regression was used to estimate risk of mortality overall and for the most common histotype, high-grade serous carcinoma. Additionally, we assessed interaction by age at diagnosis and smoking status. RESULTS: Women included in this study had a median age of 57 y, and the majority of women were obese (58%), had late-stage disease (Stage III or IV, 66%), and had high-grade serous carcinoma (64%). Greater E-DII scores including supplements (indicating greater inflammatory potential) were associated with an increased risk of mortality among women with high-grade serous carcinoma (HR1-unit change: 1.08; 95% CI: 1.01, 1.17). Similar associations were observed for the E-DII excluding supplements, although not statistically significant (HR1-unit change: 1.07; 95% CI: 0.97, 1.17). There was an interaction by smoking status, where the positive association with mortality was present only among ever smokers (HRQuartile 4/Quartile 1: 2.36; 95% CI: 1.21, 4.60) but not among never smokers. CONCLUSIONS: Greater inflammatory potential of prediagnostic diet may adversely impact prognosis among African-American women with high-grade serous carcinoma, and specifically among ever smokers.

Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women.

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls. All subjects are of African ancestry (AA). Logistic regression was performed to estimate odds ratios (OR) and 95% confidence intervals (CI). We further evaluated statistical significance of selected SNPs using the Bayesian False Discovery Probability (BFDP). A significant association with EOC was identified in the UGT2A1/2 region for the SNP rs10017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 1.2 × 10-6 , BFDP = 0.02); and an association with HGSOC was identified in the EGFR region for the SNP rs114972508 (per allele OR = 2.3, 95% CI = 1.6-3.4, P = 1.6 × 10-5 , BFDP = 0.29) and in the UGT2A1/2 region again for rs1017134 (per allele OR = 1.4, 95% CI = 1.2-1.7, P = 2.3 × 10-5 , BFDP = 0.23). Genetic variants in the EGFR and UGT2A1/2 may increase susceptibility of EOC in AA women. Future studies to validate these findings are warranted. Alterations in EGFR and UGT2A1/2 could perturb enzyme efficacy, proliferation in ovaries, impact and mark susceptibility to EOC.

Targetable Immune Regulatory Molecule Expression in High-Grade Serous Ovarian Carcinomas in African American Women: A Study of PD-L1 and IDO in 112 Cases From the African American Cancer Epidemiology Study (AACES).

African American women with high-grade serous ovarian carcinoma have worse outcomes compared with women of European descent. Although the discrepancy is partially attributed to differences in access to care, the tumor immune microenvironment may also contribute. Expression of targetable immune regulatory molecules such as programmed cell death ligand-1 (PD-L1) and indoleamine 2,3 dioxygenase (IDO) is of particular interest as it may help guide therapy in this population. Using cases from the largest study of African American women with ovarian cancer, the African American Cancer Epidemiology Study, we characterized PD-L1 and IDO expression in 112 high-grade serous ovarian carcinomas. Immunohistochemistry for PD-L1, IDO, CD8, FOX3p, and CD68 was performed. PD-L1 and IDO were scored as the percentage of positive tumor cells and tumor-associated immune cells. CD8 and FOX3p counts were averaged across 10 high-power fields. Cox proportional hazards regression was used to evaluate the association between PD-L1 and IDO expression and survival. Tumor cells were positive for PD-L1 and IDO in 29% and 58% of cases, respectively. The majority showed <10% staining, and no cases exceeded 25% positivity. The majority of PD-L1-positive cases coexpressed IDO. PD-L1 and IDO expression was associated with higher CD8 and FOX3p counts (P<0.05). No association was observed between PD-L1 and IDO and survival. In summary, expression of PD-L1 and IDO is seen in a subset of high-grade serous ovarian carcinoma from African American women and is correlated with elevated lymphocyte infiltration. While PD-L1 and IDO co-expression suggests a role for dual immunotherapy, diffuse expression of PD-L1 and IDO is rare, invoking caution regarding the potential for immunotherapeutic response.

Effect of Cultural, Folk, and Religious Beliefs and Practices on Delays in Diagnosis of Ovarian Cancer in African American Women.

BACKGROUND: Certain cultural, folk, and religious beliefs that are more common among African Americans (AAs) have been associated with later-stage breast cancer. It is unknown if these beliefs are similarly associated with delays in diagnosis of ovarian cancer. METHODS: Data from a multicenter case-control study of ovarian cancer in AA women were used to examine associations between cultural/folk beliefs and religious practices and stage at diagnosis and symptom duration before diagnosis. Associations between cultural/folk beliefs or religious practices and stage at diagnosis were assessed with logistic regression analyses, and associations with symptom duration with linear regression analyses. RESULTS: Agreement with several of the cultural/folk belief statements was high (e.g., 40% agreed that "if a person prays about cancer, God will heal it without medical treatments"), and ∼90% of women expressed moderate to high levels of religiosity/spirituality. Higher levels of religiosity/spirituality were associated with a twofold increase in the odds of stage III-IV ovarian cancer, whereas agreement with the cultural/folk belief statements was not associated with stage. Symptom duration before diagnosis was not consistently associated with cultural/folk beliefs or religiosity/spirituality. CONCLUSIONS: Women who reported stronger religious beliefs or practices had increased odds of higher stage ovarian cancer. Inaccurate cultural/folk beliefs about cancer treament were not associated with stage; however, these beliefs were highly prevalent in our population and could impact patient treatment decisions. Our findings suggest opportunities for health education interventions, especially working with churches, and improved doctor-patient communication.