Publications by authors named "Emily Wiggins"

8 Publications

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Family history of prostate cancer and prostate tumor aggressiveness in black and non-black men;results from an equal access biopsy study.

Cancer Causes Control 2021 Feb 2. Epub 2021 Feb 2.

Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, 97 Lisburn Road, Room 2.15, Belfast, BT9 7AE, UK.

Purpose: To test for racial differences in associations between family history (FH) of prostate cancer (PC) and prostate cancer aggressiveness in a racially diverse equal access population undergoing prostate biopsy.

Subjects/patients And Methods: We prospectively enrolled men undergoing prostate biopsy at the Durham Veterans Administration from 2007 to 2018 and assigned case or control status based on biopsy results. Race and FH of PC were self-reported on questionnaires. Logistic regression was used to test the association between FH and PC diagnosis overall and by tumor aggressiveness [high- (Grade Group 3-5) or low-grade (Grade Group 1-2) vs. no cancer], overall, and stratified by race. Models were adjusted for age and year of consent, race, PSA level, digital rectal exam findings, prostate volume, and previous (negative) biopsy receipt.

Results: Of 1,225 men, 323 had a FH of PC and 652 men were diagnosed with PC on biopsy. On multivariable analysis, FH was associated with increased odds of high-grade PC in black (OR 1.85, p = 0.041) and all men (OR 1.56, p = 0.057) and was unrelated to overall or low-grade PC diagnosis, overall, or stratified by race (all p ≥ 0.325). In sensitivity analyses among men without a previous biopsy, results were slightly more pronounced.

Conclusion: In this setting of equal access to care, positive FH of PC was associated with increased tumor aggressiveness in black men, but not non-black men undergoing prostate biopsy. Further research is required to tease apart the contribution of genetics from increased PC awareness potentially influencing screening and biopsy rates in men with FH.
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February 2021

Sleep quality and prostate cancer aggressiveness: Results from the REDUCE trial.

Prostate 2020 11 24;80(15):1304-1313. Epub 2020 Aug 24.

Patrick G. Johnston Centre for Cancer Research, Queen's University Belfast, Belfast, UK.

Background: Disrupted sleep has been associated with increased risk of certain cancers. Little data exist in prostate cancer. We tested the association between sleep quality and prostate cancer diagnosis overall and by tumor grade in the Reduction by Dutasteride of Prostate Cancer Events chemoprevention trial. We hypothesized that worse sleep quality would be associated with increased tumor aggressiveness.

Methods: At baseline, 5614 men completed a validated six-item questionnaire on sleep quality. We generated a composite score categorized into tertiles to measure overall sleep quality and assessed each sleep quality question individually. Logistic regression was used to test associations between baseline sleep quality and overall, low-grade and high-grade prostate cancer diagnosis at 2-year study-mandated biopsy. Models were stratified by nocturia.

Results: Overall sleep quality was unrelated to overall or low-grade prostate cancer. Worse overall sleep quality was associated with elevated odds of high-grade prostate cancer (odds ratio [OR] 1.15; 95% confidence interval [CI]: 0.83-1.60 and OR 1.39; 95% CI: 1.01-1.92). Men reporting trouble falling asleep at night sometimes vs never had elevated odds of high-grade prostate cancer (OR: 1.51; 95% CI: 1.08-2.09) while trouble staying awake during the day was associated with decreased odds of low-grade prostate cancer (OR: 0.65; 95% CI: 0.49-0.86). Results were similar within strata of nocturia severity.

Conclusions: Overall, associations between sleep quality and prostate cancer were inconsistent. However, there was some evidence for a positive association between insomnia and high-grade prostate cancer, and an inverse relationship between daytime sleepiness and low-grade prostate cancer; findings that should be validated by future studies.
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November 2020

Soluble Endoglin (sCD105) as a Novel Biomarker for Detecting Aggressive Prostate Cancer.

Anticancer Res 2020 Mar;40(3):1459-1462

Division of Hematology/Oncology, Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A.

Background/aim: We have previously found elevated levels of endoglin (CD105) in the prostate cancer (PC) tissue of men with poor prognosis, compared to men with indolent disease. Herein, we examined whether plasma levels of the soluble form of CD105 (sCD105) differ according to the PC grade at diagnosis.

Patients And Methods: We measured sCD105 in 73 subjects with biopsy-confirmed PC at the Durham, North Carolina, Veteran Affairs Health System. The association between sCD105 and intermediate/high-grade PC risk [Gleason Group (GG) 2-5 vs. 1] was examined using regression models.

Results: Of 73 men, 27 had low-grade PC and 46 high-grade PC. Higher GG was linked to lower sCD105 (GG1: 6938 pg/ml, GG2-3: 6150 pg/ml, GG4-5: 5554 pg/ml; p=0.012). On multivariable analysis, lower sCD105 was associated with increased high-grade PC risk (OR=1.33, p=0.028).

Conclusion: Lower sCD105 levels were associated with intermediate and high-risk PC. Further investigation is warranted in a larger PC cohort.
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March 2020

A Randomized Controlled Trial of a 6-Month Low-Carbohydrate Intervention on Disease Progression in Men with Recurrent Prostate Cancer: Carbohydrate and Prostate Study 2 (CAPS2).

Clin Cancer Res 2020 06 27;26(12):3035-3043. Epub 2020 Feb 27.

Duke University School of Medicine, Durham, North Carolina.

Purpose: Both weight loss and low-carbohydrate diets (LCD) without weight loss prolong survival in prostate cancer models. Few human trials have tested weight loss or LCD on prostate cancer.

Experimental Design: We conducted a multi-site randomized 6-month trial of LCD versus control on PSA doubling time (PSADT) in patients with prostate cancer with biochemical recurrence (BCR) after local treatment. Eligibility included body mass index (BMI) ≥ 24 kg/m and PSADT 3 to 36 months. The LCD arm was instructed to eat [Formula: see text]20 g/carbs/day; the control arm instructed to avoid dietary changes. Primary outcome was PSADT. Secondary outcomes included weight, lipids, glucose metabolism, and diet.

Results: Of 60 planned patients, the study stopped early after an interim analysis showed futility. Twenty-seven LCD and 18 control patients completed the study. At 6 months, although both arms consumed similar protein and fats, the LCD arm reduced carbohydrates intake (-117 vs. 8 g, < 0.001) and lost weight (-12.1 vs. -0.50 kg, < 0.001). The LCD arm reduced HDL, triglycerides, and HbA1c with no difference in total cholesterol or glucose. Mean PSADT was similar between LCD (21 months) and control (15 months, = 0.316) arms. In a exploratory analysis accounting for prestudy PSADT, baseline PSA, primary treatment, and hemoconcentration, PSADT was significantly longer in LCD versus control (28 vs. 13 months, = 0.021) arms. Adverse events were few, usually mild, and returned to baseline by 6 months.

Conclusions: Among BCR patients, LCD induced weight loss and metabolic benefits with acceptable safety without affecting PSADT, suggesting LCD does not adversely affect prostate cancer growth and is safe. Given exploratory findings of longer PSADT, larger studies testing LCD on disease progression are warranted.
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June 2020

Natural killer cell activity and prostate cancer risk in veteran men undergoing prostate biopsy.

Cancer Epidemiol 2019 10 1;62:101578. Epub 2019 Aug 1.

Department of Surgery, Division of Urology, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA; Surgery Section, Durham VA Health Care System, Durham, NC, USA.

Background: A previous pilot study found that men with a positive prostate biopsy had low numbers of circulating natural killer (NK) cells, compared to biopsy negative men.

Methods: To confirm these data, we analyzed differences in NK cells from 94 men undergoing prostate biopsy to determine whether NK cells could predict for a positive biopsy. NK cells activity (NKA) was measured by an in vitro diagnostic system, with a pre-defined cut-off value for NKA at 200 pg/mL. Logistic regression and receiver operator characteristics (Area Under the Curve (AUC)) analyses were used to test the diagnostic value of NKA.

Results: The NKA test performance showed specificity of 88%, positive predictive value of 84%, sensitivity of 34%, and a negative predictive value of 41%. Among the 94 men analyzed, NKA was not significantly linked with age, race, digital rectal examination (DRE), prostate volume, PSA or biopsy grade group (all P ≥ 0.14). In multivariable logistic regression analysis, the odds ratio (OR) of low NKA (<200 pg/mL) for the detection of PC was 4.89, 95%CI 1.34-17.8, with a ROC area under the curve of 0.79 in all participants and increasing to 0.83 and 0.85 for the detection of PC and high-grade PC, respectively, among men with a normal DRE.

Conclusions: Men with a low NKA value had five-times higher odds of PC at biopsy. The implementation of this NKA assay in the clinic together with PSA may help to advise patients with the highest risk of PC whether, or not, to undergo a prostate biopsy.
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October 2019

Facilitators and Barriers to the Implementation of the HPV VACs (Vaccinate Adolescents Against Cancers) Program: A Consolidated Framework for Implementation Research Analysis.

Prev Chronic Dis 2019 07 3;16:E85. Epub 2019 Jul 3.

Rollins School of Public Health, Emory University, Atlanta, Georgia.

Purpose And Objectives: The human papillomavirus (HPV) vaccine is an effective but underused method for preventing multiple cancers, particularly cervical cancer. Although interventions have successfully targeted barriers to HPV vaccine uptake in various clinical settings, few studies have explored their implementation. Our study examines the delivery of the HPV VACs (Vaccinate Adolescents Against Cancer) Program and elicits information on barriers and facilitators to implementation.

Intervention Approach: The VACs Program pilot was a multilevel, evidence-based intervention conducted by the American Cancer Society in 30 federally qualified health centers (FQHCs) in the United States.

Evaluation Methods: We conducted in-depth interviews (N = 32) by telephone with representatives of 9 FQHC partners. We structured the interview guides on Consolidated Framework for Implementation Research (CFIR) domains. We asked about project start-up activities, implementation strategy selection, policy- and practice-level changes, staffing structure, challenges, and key factors leading to project success. At least 2 researchers coded each interview transcript verbatim.

Results: Participants most frequently identified the electronic health record system, training and education, concrete tools and resources, and provider champions as facilitators to implementing HPV VACs. Limited staff resources, challenges of electronic health records, issues with state immunization registries, patient misinformation about vaccines and vaccine stigma, cultural/language barriers, competing priorities, levels of funding, staff buy-in, training needs, and low health literacy were identified as barriers.

Implications For Public Health: Providing appropriate training for FQHC staff members and providers along with technical assistance and facilitation tools were critical for increasing provider confidence in recommending HPV vaccine. Addressing capacity-building and implementation barriers in FQHCs can increase effective implementation of evidence-based interventions to increase HPV vaccination uptake and reduce the burden of future cancers.
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July 2019

Low circulating levels of the mitochondrial-peptide hormone SHLP2: novel biomarker for prostate cancer risk.

Oncotarget 2017 Nov 10;8(55):94900-94909. Epub 2017 Aug 10.

Division of Urology, Veterans Affairs Medical Center, Durham, North Carolina, USA.

Context: Mitochondrial DNA mutations and dysfunction are associated with prostate cancer (PCa). Small humanin-like peptide-2 (SHLP2) is a novel mitochondrial-encoded peptide and an important mitochondrial retrograde signaling molecule.

Objective: To determine whether serum SHLP2 concentration is associated with PCa risk and whether associations are race-specific.Design, Setting and Participants: Patients undergoing prostate biopsy were recruited from the Durham Veterans Affairs hospital. Serum was collected prior to biopsy and SHLP2 measured by ELISA. We selected 200 men for analysis (100 negative biopsies and 100 PCa cases; 100 black and 100 white).

Results: Mean SHLP2 levels were significantly higher in white controls versus black controls and SHLP2 was significantly higher in white controls versus white PCa cases. In contrast, there was no significant difference in SHLP2 levels between black controls and black cases. SHLP2 levels > 350-pg/ml ruled out PCa with ≥ 95% accuracy in both races.

Conclusions: Lower SHLP2 was linked with increased PCa risk in white men, but no significant association was observed in black men. While SHLP2 > 350-pg/ml ruled out PCa in both races with high accuracy, SHLP2 was unrelated to PCa grade. These data suggest the circulating mitochondrial-derived peptide hormone, SHLP2 plays a key role in the development and racial disparity of prostate cancer.
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November 2017

UDP-glucuronosyltransferases and biochemical recurrence in prostate cancer progression.

BMC Cancer 2017 Jul 3;17(1):463. Epub 2017 Jul 3.

Cedars-Sinai Health System, Center for Integrated Research on Cancer and Lifestyle, Cancer Genetics and Prevention Program, Surgery, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.

Background: Uridine 5'-diphosphate-glucuronosyltransferase 2B (UGT2B) genes code for enzymes that catalyze the clearance of testosterone, dihydrotestosterone (DHT), and DHT metabolites in the prostate basal and luminal tissue. The expression of the UGT2B15, UGT2B17, and UGT2B28 enzymes has not been evaluated in prostate tissue samples from hormone therapy-naïve patients.

Methods: We determined the expression of UGT2B15, UGT2B17, and UGT2B28 enzymes in 190 prostate tissue samples from surgical specimens of a multiethnic cohort of patients undergoing radical prostatectomy at the Durham Veterans Affairs Medical Center. The association between each protein's percent positive and H-score, a weighted score of staining intensity, and the risk of biochemical recurrence (BCR) was tested using separate Cox proportional hazards models. In an exploratory analysis, UGT2B17 total positive and H-score were divided at the median and we tested the association between UGT2B17 group and risk of BCR.

Results: The median follow-up for all patients was 118 months (IQR: 85-144). Of 190, 83 (44%) patients developed BCR. We found no association between UGT2B15 or UGT2B28 and risk of BCR. However, there was a trend for an association between UGT2B17 and BCR (HR = 1.01, 95% CI 1.00-1.02, p = 0.11), though not statistically significant. Upon further investigation, we found that patients with UGT2B17 higher levels of expression had a significant increased risk of BCR on univariable analysis (HR = 1.57, 95% CI 1.02-2.43, p = 0.041), although this association was attenuated in the multivariable model (HR = 1.50, 95% CI 0.94-2.40, p = 0.088).

Conclusions: Our findings suggest that UGT2B17 overexpression may be associated with a significant increased risk of BCR. These results are consistent with previous reports which showed UGT2B17 significantly expressed in advanced prostate cancer including prostate tumor metastases.
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July 2017