Dataset Information

Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

ABSTRACT: African American men have the highest rates of prostate cancer incidence and mortality in the United States. Understanding underlying reasons for this disparity could identify preventive interventions important to African American men.To determine whether the association of obesity with prostate cancer risk differs between African American and non-Hispanic white men and whether obesity modifies the excess risk associated with African American race.Prospective study of 3398 African American and 22,673 non-Hispanic white men who participated in the Selenium and Vitamin E Cancer Prevention Trial (2001-2011) with present analyses completed in 2014.Total, low-grade (Gleason score <7), and high-grade (Gleason score ?7) prostate cancer incidence.With a median (interquartile range) follow-up of 5.6 (1.8) years, there were 270, 148, and 88 cases of total, low-, and high-grade prostate cancers among African American men and a corresponding 1453, 898, and 441 cases in non-Hispanic white men, respectively. Although not associated with risk among non-Hispanic white men, BMI was positively associated with an increase in risk among African American men (BMI, <25 vs ?35: hazard ratio [HR], 1.49 [95% CI, 0.95, 2.34]; P for trend?=?.03). Consequently, the risk associated with African American race increased from 28% (HR, 1.28 [95% CI, 0.91-1.80]) among men with BMI less than 25 to 103% (HR, 2.03 [95% CI, 1.38-2.98]) among African American men with BMI at least 35 (P for trend?=?.03). Body mass index was inversely associated with low-grade prostate cancer risk within non-Hispanic white men (BMI, <25 vs ?35: HR, 0.80 [95% CI, 0.58-1.09]; P for trend?=?.02) but positively associated with risk within African American men (BMI, <25 vs ?35: HR, 2.22 [95% CI, 1.17-4.21]; P for trend?=?.05). Body mass index was positively associated with risk of high-grade prostate cancer in both non-Hispanic white men (BMI, <25 vs ?35: HR, 1.33 [95% CI, 0.90-1.97]; P for trend?=?.01) and African American men, although the increase may be larger within African American men, albeit the racial interaction was not statistically significant (BMI, <25 vs ?35: HR, 1.81 [95% CI, 0.79-4.11]; P for trend?=?.02).Obesity is more strongly associated with increased prostate cancer risk among African American than non-Hispanic white men and reducing obesity among African American men could reduce the racial disparity in cancer incidence. Additional research is needed to elucidate the mechanisms underlying the differential effects of obesity in African American and non-Hispanic white men.

SUBMITTER: Barrington WE

PROVIDER: S-EPMC4570268 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Barrington Wendy E WE Schenk Jeannette M JM Etzioni Ruth R Arnold Kathryn B KB Neuhouser Marian L ML Thompson Ian M IM Lucia M Scott MS Kristal Alan R AR

JAMA oncology 20150601 3

<h4>Importance</h4>African American men have the highest rates of prostate cancer incidence and mortality in the United States. Understanding underlying reasons for this disparity could identify preventive interventions important to African American men.<h4>Objective</h4>To determine whether the association of obesity with prostate cancer risk differs between African American and non-Hispanic white men and whether obesity modifies the excess risk associated with African American race.<h4>Design, ...[more]

PMID: 26181184

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Project description:ImportanceProspective evidence suggests abiraterone is associated with superior progression-free survival for African American men compared with non-Hispanic White men with metastatic castration-resistant prostate cancer (mCRPC).ObjectiveTo investigate differences in outcomes with first-line abiraterone therapy between African American and non-Hispanic White men with mCRPC in a national real-world cohort.Design, setting, and participantsThis retrospective cohort study used a nationwide electronic health record-derived database of 3808 men receiving first-line therapy for mCRPC between January 1, 2012, and December 31, 2018. Data analysis was performed between January 1, 2020, and June 1, 2021. Median follow-up was 13 months (IQR, 7-22 months). Propensity score-based inverse probability of treatment weighting was applied to reduce imbalance in measured confounders between patients receiving first-line abiraterone vs other first-line therapies. Deidentified patient data originated from a geographically diverse set of approximately 280 cancer clinics (approximately 800 sites of care) throughout the United States. Participants had newly diagnosed mCRPC and were receiving first-line systemic therapy during the study period.ExposuresReceipt of abiraterone for first-line therapy.Main outcomes and measuresOverall survival from start of first-line treatment. Stratified analyses investigated overall survival within each race group, with first-line enzalutamide as the comparator.ResultsAmong 3808 patients with mCRPC, there were 2615 non-Hispanic White men (68.7%; mean [SD] age at diagnosis, 74 [8] years) and 404 African American men (10.6%; mean [SD] age at diagnosis, 69 [9] years), and 1729 patients (45.4%) in the cohort received first-line abiraterone. Among patients receiving first-line abiraterone, African American men had higher median overall survival than non-Hispanic White men (23 months [IQR, 10-37 months] vs 17 months [IQR, 9-32 months], respectively; inverse probability of treatment weighting hazard ratio, 0.76; 95% CI, 0.60-0.98). A race-by-treatment interaction existed for first-line abiraterone vs first-line enzalutamide (hazard ratio for abiraterone vs enzalutamide: non-Hispanic White men, 1.21 [95% CI, 1.06-1.38]; African American men, 1.05 [95% CI, 0.74-1.50]; interaction P = .02). There was no overall survival difference between first-line abiraterone and first-line enzalutamide among African American patients (24 vs 24 months, respectively; inverse probability of treatment weighting hazard ratio, 1.05; 95% CI, 0.74-1.50). First-line abiraterone was associated with decreased median overall survival relative to first-line enzalutamide among non-Hispanic White patients (17 months [IQR, 9-32 months] vs 20 months [IQR, 10-36 months], respectively; inverse probability of treatment weighting hazard ratio, 1.21; 95% CI, 1.06-1.38).Conclusions and relevanceIn this cohort study of patients who received first-line systemic therapy for mCRPC, African American men who received abiraterone had improved overall survival compared with non-Hispanic White men. Future prospective studies should assess drivers of differential abiraterone outcomes in mCRPC between African American and non-Hispanic White men, including differences in genetic factors and socioeconomic status, to inform treatment strategies.

Project description:The incidence and mortality rates of prostate cancer are significantly higher in African-American men when compared to European-American men. We tested the hypothesis that differences in tumor biology contribute to this survival health disparity. Using microarray technology, we obtained gene expression profiles of primary prostate tumors resected from 33 African-American and 36 European-American patients. These tumors were matched on clinical parameters. We also evaluated 18 non-tumor prostate tissues from 7 African-American and 11 European-American patients. The resulting datasets were analyzed for expression differences on the gene and pathway level comparing African-American with European-American patients. Our analysis revealed a significant number of genes, e.g., 162 transcripts at a false-discovery rate less than 5%, to be differently expressed between African-American and European-American patients. Using a disease association analysis, we identified a common relationship of these transcripts with autoimmunity and inflammation. These findings were corroborated on the pathway level with numerous differently expressed genes clustering in immune response, stress response, cytokine signaling, and chemotaxis pathways. Furthermore, a two-gene tumor signature was identified that accurately differentiated between African-American and European-American patients. This finding was confirmed in a blinded analysis of a second sample set. In conclusion, the gene expression profiles of prostate tumors indicate prominent differences in tumor immunobiology between African-American and European-American men. The profiles portray the existence of a distinct tumor microenvironment in these two patient groups. Experiment Overall Design: A total of 69 fresh-frozen prostate tumors were obtained from the NCI Cooperative Prostate Cancer Tissue Resource (CPCTR) and the Department of Pathology at the University of Maryland (UMD). All tumors were resected adenocarcinomas that had not received any therapy prior to prostatectomy. The macro-dissected CPCTR tumor specimens (n = 59) were reviewed by a CPCTR-associated pathologist, who confirmed the presence of tumor in the specimens. These tissues were collected between 2002 and 2004 at four different sites, with each site providing tissues from both African-American and European-American patients. Information on race/ethnicity (33 African-Americans and 36 European-Americans) was either extracted from medical records (CPCTR) or obtained through an epidemiological questionnaire in which race/ethnicity was self-reported (UMD). Only one patient, a European-American, was also Hispanic. Surrounding non-tumor prostate tissue was collected from 18 of the recruited patients in this study. Of those, 7 were African-American men and 11 were European-American men. We also isolated total RNA from 10 needle biopsy specimens collected from patients at the National Naval Medical Center (one African-American and 9 European-Americans) that did not have prostate cancer. From those, we prepared two RNA pools, each representing 5 patients. Clinicopathological characteristics of the patients, including age at prostatectomy, histology, Gleason score, pathological stage, PSA at diagnosis, tumor size, extraprostatic extension, margin involvement, and seminal vesicle invasion were obtained from CPCTR. For UMD cases, this information was extracted from the medical and pathology records, if available. Written informed consent was obtained from all donors. Tissue collection and study design were approved by the institutional review boards of the participating institutions.

Project description:BackgroundVitamin D may protect against breast cancer. Although Black/African American women and Hispanic/Latina women have lower circulating vitamin D levels than non-Hispanic White women, few studies have examined the association between vitamin D and breast cancer within these racial/ethnic groups.MethodsThe vitamin D-breast cancer association was evaluated using a case-cohort sample of self-identified Black/African American and non-Black Hispanic/Latina women participating in the US-wide Sister Study cohort. Circulating 25-hydroxyvitamin D (25(OH)D) and 24,25-dihydroxyvitamin D (24,25(OH)2D) were measured using liquid chromatography-tandem mass spectrometry in blood samples collected at the baseline from 415 women (290 Black/African American women and 125 non-Black Hispanic/Latina women) who developed breast cancer. These were compared to concentrations in 1545 women (1084 Black/African American women and 461 Hispanic/Latina women) randomly selected from the cohort. Multivariable-adjusted Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).ResultsOver a mean follow-up of 9.2 years, women with circulating 25(OH)D concentrations above the clinical cut point for deficiency (20.0 ng/mL) had lower breast cancer rates than women with concentrations ≤ 20 ng/mL (HR, 0.79; 95% CI, 0.61-1.02). The inverse association was strongest among Hispanic/Latina women (HR, 0.52; 95% CI, 0.29-0.93), with a weaker association observed among Black/African American women (HR, 0.89; 95% CI, 0.68-1.18; P for heterogeneity = 0.13). There were no clear differences by menopausal status, follow-up time, estrogen receptor status, or invasiveness. Neither 24,25(OH)2 D nor the 24,25(OH)2 D to 25(OH)D ratio were independently associated with breast cancer risk.ConclusionsThis prospective study supports the hypothesis that vitamin D may be protective against breast cancer incidence in women, including non-Black Hispanic/Latina and Black/African American women.Lay summaryVitamin D may protect against breast cancer. Although women of color have lower average vitamin D levels than non-Hispanic White women, few studies have considered the role of race/ethnicity. In a sample of self-identified Black/African American and Hispanic/Latina women, we observed that vitamin D concentrations measured in blood were inversely associated with breast cancer, particularly among Latinas. These findings indicate that vitamin D may protect women against breast cancer, including those in racial/ethnic groups with low average circulating levels.

Dataset Information

Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

Publications

Difference in Association of Obesity With Prostate Cancer Risk Between US African American and Non-Hispanic White Men in the Selenium and Vitamin E Cancer Prevention Trial (SELECT).

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