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Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.Design, setting, and participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.Outcome measurements and statistical analysis: Common genotyped and imputed variants were tested for their association with PCa risk. Novel susceptibility loci were identified and incorporated into a multiancestry polygenic risk score (PRS). The PRS was evaluated for associations with PCa risk and disease aggressiveness.Results and limitations: Nine novel susceptibility loci for PCa were identified, of which seven were only found or substantially more common in men of African ancestry, including an African-specific stop-gain variant in the prostate-specific gene anoctamin 7 (ANO7). A multiancestry PRS of 278 risk variants conferred strong associations with PCa risk in African ancestry studies (odds ratios [ORs] >3 and >5 for men in the top PRS decile and percentile, respectively). More importantly, compared with men in the 40-60% PRS category, men in the top PRS decile had a significantly higher risk of aggressive PCa (OR = 1.23, 95% confidence interval = 1.10-1.38, p = 4.4 × 10-4).Conclusions: This study demonstrates the importance of large-scale genetic studies in men of African ancestry for a better understanding of PCa susceptibility in this high-risk population and suggests a potential clinical utility of PRS in differentiating between the risks of developing aggressive and nonaggressive disease in men of African ancestry.Patient summary: In this large genetic study in men of African ancestry, we discovered nine novel prostate cancer (PCa) risk variants. We also showed that a multiancestry polygenic risk score was effective in stratifying PCa risk, and was able to differentiate risk of aggressive and nonaggressive disease.

International audience; Although men of African ancestry have a high risk of prostate cancer (PCa), no genes or mutations have been identified that contribute to familial clustering of PCa in this population. We investigated whether the African ancestry-specific PCa risk variant at 8q24, rs72725854, is enriched in men with a PCa family history in 9052 cases, 143 cases from high-risk families, and 8595 controls of African ancestry. We found the risk allele to be significantly associated with earlier age at diagnosis, more aggressive disease, and enriched in men with a PCa family history (32% of high-risk familial cases carried the variant vs 23% of cases without a family history and 12% of controls). For cases with two or more first-degree relatives with PCa who had at least one family member diagnosed at age

Integrating data across heterogeneous research environments is a key challenge in multi-site, collaborative research projects. While it is important to allow for natural variation in data collection protocols across research sites, it is also important to achieve interoperability between datasets in order to reap the full benefits of collaborative work. However, there are few standards to guide the data coordination process from project conception to completion. In this paper, we describe the experiences of the Clinical Sequence Evidence-Generating Research (CSER) consortium Data Coordinating Center (DCC), which coordinated harmonized survey and genomic sequencing data from seven clinical research sites from 2020 to 2022. Using input from multiple consortium working groups and from CSER leadership, we first identify 14 lessons learned from CSER in the categories of communication, harmonization, informatics, compliance, and analytics. We then distill these lessons learned into 11 recommendations for future research consortia in the areas of planning, communication, informatics, and analytics. We recommend that planning and budgeting for data coordination activities occur as early as possible during consortium conceptualization and development to minimize downstream complications. We also find that clear, reciprocal, and continuous communication between consortium stakeholders and the DCC is equally important to maintaining a secure and centralized informatics ecosystem for pooling data. Finally, we discuss the importance of actively interrogating current approaches to data governance, particularly for research studies that straddle the research-clinical divide.

Background Calcium and dairy product intakes have been positively associated with prostate cancer risk. An imbalance in concentrations of calcium and magnesium has been associated with multiple chronic diseases, although few studies have examined the relation with prostate cancer aggressiveness. Objective The goal of this study was to examine the association between dietary intakes of calcium and magnesium, the calcium-to-magnesium ratio (Ca:Mg), and dairy products and prostate cancer aggressiveness. Design Dietary intake was assessed with the use of an interviewer-administered modified National Cancer Institute Diet History Questionnaire in 996 African American and 1064 European American men with a recent histologically confirmed diagnosis of prostate cancer from the North Carolina-Louisiana Prostate Cancer Project (PCaP). High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) >20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4. The comparison group was all other prostate cancer cases. Logistic regression was used to determine the adjusted ORs and 95% CIs for high-aggressive prostate cancer by tertile of diet and supplement exposures. Results There was a positive association across tertiles of dietary Ca:Mg intake, with odds of high-aggressive prostate cancer in the upper tertiles as follows-OR for tertile 2 compared with tertile 1: 1.38 (95% CI: 1.01, 1.88); OR for tertile 3 compared with tertile 1: 1.46 (95% CI: 1.06, 2.02). When stratified by race, the positive association was more pronounced in African American men (OR for tertile 3 compared with tertile 2: 1.62; 95% CI: 1.04, 2.53). Men who reported the highest daily consumption of whole-fat milk had a 74% increased odds of high-aggressive prostate cancer compared with non-whole-fat milk drinkers, which was attenuated after adjustment for potential mediating factors, such as saturated fat and Ca:Mg intake. Conclusions Among both African American and European American men diagnosed with prostate cancer, a higher Ca:Mg and whole-milk intake were associated with higher odds of high-aggressive prostate cancer. This study was registered at www.clinicaltrials.gov as NCT03289130.

This study aims to (1) describe the activities, function, and health-related quality of life (HRQOL) of a large sample of older adults (age ≥65) with cancer, (2) identify the associations with demographics, cancer type, comorbid conditions, and ability to participate in activities and functional status.The Health Registry/Cancer Survivorship Cohort is an institutional database designed to aid cancer survivorship research. The registry includes three measures of patient-reported HRQOL: FACT-G and PROMIS® Global measures for physical and mental health. Other measures included in the registry are cancer type, date from diagnosis, number of comorbid conditions and specific conditions and their limitations in daily activity, and self-reported daily activity/function.Our sample consists of 768 older adults with cancer, mean age 72years, 60% female, and 90% White. Mean scores for HRQOL: FACT-G (85, range: 25-108), PROMIS-physical (48, range: 16-67) and, PROMIS-mental (51, range: 21-67). In multivariable models, Black race, one or more comorbid conditions, and Gastrointestinal cancer (p.05), and patient- reported decreased levels of activities/function were all independently associated with poor HRQOL (p.0001).Older Black adults with cancer, those that have high comorbidity burden, with gastrointestinal cancers and those that report decreased ability to participate in daily activities/function reported poorer HRQOL. As geriatric oncology moves towards trying to identify who may need supportive services, this study demonstrated that a one question patient-reported level of activities and functional ability were independently associated with physical, mental, and cancer-specific HRQOL.

Objective To examine associations between non-modifiable patient factors and patient satisfaction (PS) among women presenting to a gynecologic oncology clinic. Methods This is a cross sectional analysis of patients presenting for surgical management by a gynecologic oncologist at a tertiary care academic medical center. The Patient Satisfaction Questionnaire (PSQ-18) that measures PS in seven domains of health care was administered. Scores were converted to "satisfied" versus "unsatisfied/equivocal". Demographic and medical factors were obtained from the medical record. Chi-square, t -tests, and multivariable logistic regression were used. Results 208 patients completed the baseline patient satisfaction questionnaire and the median PSQ-18 score was 70.5 (range: 42–90). Median age was 58years (range: 22–93). Several non-modifiable factors were associated with PS. White patients had higher interpersonal PS than minorities (86% v 65%, p =0.002). The uninsured had lower interpersonal (60% v 86%, p =0.003) and accessibility PS (33% v 67%, p =0.03). Increasing education and less time travelled to care were both associated with higher interpersonal ( p =0.03, p =0.05) and accessibility PS ( p =0.01, p =0.01). There was no association between clinical factors (BMI, comorbidities, cancer) and PS. In multivariable analysis, the strongest predictor of interpersonal PS was white race while the strongest predictors of accessibility PS were time travelled to care and insurance status. Conclusions Patient satisfaction scores among patients presenting to a gynecologic oncology clinic are associated with non-modifiable demographic, financial and geographic factors. Pay for performance measures that use summed patient satisfaction scores may penalize hospitals for patient-mix driven differences.

Quality of life (QoL) for women with gynecologic malignancies is predictive of chemotherapy related toxicity and overall survival but has not been studied in relation to surgical outcomes and hospital readmissions. Our goal was to evaluate the association between baseline, pre-operative QoL measures and 30-day post-operative morbidity and health resource utilization by gynecologic oncology patients.We analyzed prospectively collected survey data from an institution-wide cohort study. Patients were enrolled from 8/2012 to 6/2013 and medical record data was abstracted (demographics, comorbid conditions, and operative outcomes). Responses from several validated health-related QoL instruments were collected. Bivariate tests and multivariable linear and logistic regression models were used to evaluate factors associated with QoL scores.Of 182 women with suspected gynecologic malignancies, 152 (84%) were surveyed pre-operatively and 148 (81%) underwent surgery. Uterine (94; 63.5%), ovarian (26; 17.5%), cervical (15; 10%), vulvar/vaginal (8; 5.4%), and other (5; 3.4%) cancers were represented. There were 37 (25%) cases of postoperative morbidity (PM), 18 (12%) unplanned ER visits, 9(6%) unplanned clinic visits, and 17 (11.5%) hospital readmissions (HR) within 30days of surgery. On adjusted analysis, lower functional well-being scores resulted in increased odds of PM (OR 1.07, 95%CI 1.01-.1.21) and HR (OR 1.11, 95%CI 1.03-1.19). A subjective global assessment score was also strongly associated with HR (OR 1.89, 95%CI 1.14, 3.16).Lower pre-operative QoL scores are significantly associated with post-operative morbidity and hospital readmission in gynecologic cancer patients. This relationship may be a novel indicator of operative risk.

Disclaimer The views expressed in this manuscript are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the US Government. Objective The purpose of this study was to explore whether a particular combination of individual characteristics influences patient satisfaction with the health care system among a sample of African American men in North Carolina with prostate cancer. Patient satisfaction may be relevant for improving African American men’s use of regular care, thus improving the early detection of prostate cancer and attenuating racial disparities in prostate cancer outcomes. Methods This descriptive correlation study examined relationships of individual characteristics that influence patient satisfaction using data from 505 African American men from North Carolina, who prospectively enrolled in the North Carolina-Louisiana Prostate Cancer Project from September 2004 to November 2007. Analyses consisted of univariate statistics, bivariate analysis, and multiple regression analysis. Results The variables selected for the final model were: participation in religious activities, mistrust, racism, and perceived access to care. In this study, both cultural variables, mistrust ( p = p = F = 5.59), were significantly negatively associated with patient satisfaction and accounted for the majority of the variability represented by individual characteristics. Conclusion Mistrust and racism are cultural factors that are extremely important and have been negatively associated with patient satisfaction and decreased desires to utilize health care services for African American men. To overcome barriers in seeking health care services, health care providers need to implement a patient-centered approach by creating a clinical environment that demonstrates cultural competence and eliminating policies, procedures, processes, or personnel that foster mistrust and racism.

A dense gene-based SNP map was constructed across a 360-kb region containing the interleukin-1 gene cluster (IL1A, IL1B, and IL1RN), focusing on IL1RN. In total, 95 polymorphisms were confirmed or identified primarily by direct sequencing. Polymorphisms were precisely mapped to completed BAC and genomic sequences spanning this region. The polymorphisms were typed in 443 case-control subjects from Caucasian and African American groups. Consecutive pair-wise marker linkage disequilibrium was not strictly correlated with distance and ranged from D'=0.0079 to 1.000 and D'=0.0521 to 1.0000 in Caucasians and African Americans, respectively. Single markers and haplotypes in IL1 cluster genes were evaluated for association with end-stage renal disease (ESRD). Eleven SNPs show some evidence of association with ESRD, with the strongest associations in two IL1A variants, one SNP, rs1516792-3, in intron 5 (p=0.0015) and a 4-bp insertion/deletion within the 3'UTR, rs16347-2 (p=0.0024), among African Americans with non-T2DM-associated ESRD.

Association of an IL-1A 3′UTR polymorphism with end-stage renal disease and IL-1α expression. Background We evaluated polymorphisms in the interleukin-1 alpha 3′-untranslated region ( IL-1A 3′[UTR]) for association with type 2 diabetes–associated (DM) and nondiabetic-associated (non-DM) end-stage renal disease (ESRD) in two ethnic groups. Methods 3′UTR polymorphisms were identified by alignment of overlapping human expressed sequence tags (ESTs). Sequence ambiguities were experimentally confirmed and variants genotyped to test for association with ESRD in 75 unrelated Caucasians with DM ESRD, 95 unrelated Caucasian controls and, in a parallel study, 92 unrelated African Americans with type 2 DM ESRD, 95 unrelated African Americans with non-DM ESRD, and 86 unrelated African American controls. IL-1A 3′ UTR genotype and lipopolysaccharide (LPS)-stimulated IL-1α protein levels were measured in healthy Caucasians ( N = 112) and African Americans ( N = 101) to evaluate association between genotype and protein level. Results A polymorphism in the 3′ UTR of the human IL-1A gene was associated with ESRD and IL-1α protein expression. The polymorphism consists of two single nucleotide polymorphisms (SNPs) and an insertion/deletion generating four different haplotypes: TN 7 TTCAA, AN 7 TTCAA, TN 7 TTCAG and an allele deleted for four internal bases, TN 7 ( del TTCA)A. The 4 bp deletion allele, TN 7 ( del TTCA)A, was significantly less common among Caucasian DM ESRD and African American non-DM ESRD patients (recessive model; P = 0.0364 and P = 0.0293, respectively). In vitro, this polymorphism is associated with the amount of IL-1α protein synthesized in LPS-stimulated lymphocytes from healthy subjects ( P = 0.0013, additive model), with the TN 7 ( del TTCA)A haplotype associated with higher levels of stimulated IL-1α. Conclusion The association of the TN 7 ( del TTCA)A haplotype with higher levels of IL-1α expression and reduced risk for ESRD is consistent with involvement of cytokines in risk for developing nephropathy.

Detailed medical family history data have been proposed to be effective in identifying high-risk families for targeted intervention. With use of a validated and standardized quantitative family risk score (FRS), the degree of familial aggregation of coronary heart disease (CHD), stroke, hypertension, and diabetes was obtained from 122,155 Utah families and 6,578 Texas families in the large, population-based Health Family Tree Study, and 1,442 families in the NHLBI Family Heart Study in Massachusetts, Minnesota, North Carolina, and Utah. Utah families with a positive family history of CHD (FRSor =0.5) represented only 14% of the general population but accounted for 72% of persons with early CHD (men before age 55 years, women before age 65 years) and 48% of CHD at all ages. For strokes, 11% of families with FRSor =0.5 accounted for 86% of early strokes (75 years) and 68% of all strokes. Analyses of5,000 families sampled each year in Utah for 14 years demonstrated a gradual decrease in the frequency of a strong positive family history of CHD (-26%/decade) and stroke (-15%/decade) that paralleled a decrease in incidence rates (r = 0.86, p0.001 for CHD; r = 0.66, p0.01 for stroke). Because of the collaboration of schools, health departments, and medical schools, the Health Family Tree Study proved to be a highly cost-efficient method for identifying 17,064 CHD-prone families and 13,106 stroke-prone families (at a cost of about $27 per high-risk family) in whom well-established preventive measures can be encouraged. We conclude that most early cardiovascular events in a population occur in families with a positive family history of cardiovascular disease. Family history collection is a validated and relatively inexpensive tool for family-based preventive medicine and medical research.