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Patient and clinical characteristics of Caucasian and African American statin users and non-users.

Logistic regression analysis of associations between statin use and prostate cancer aggressiveness, additionally adjusted for education, income and family history of prostate cancer.

Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use.Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association.Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56–0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45–1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41–1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53–1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25–0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59–1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70–2.64).Conclusions: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers.Impact: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670–7. ©2016 AACR.

Logistic regression analysis of associations between statin use and prostate cancer aggressiveness, excluding men using non-statin cholesterol-lowering drugs.

The metabolic landscape of the prostate changes with malignant transformation, and metabolomics is a means of identifying diagnostic and prognostic biomarkers for prostate cancer. Epidemiology and registry studies containing archival formalin-fixed paraffin-embedded (FFPE) specimens are a rich resource for this work but this method of tissue preservation presents a challenge due to loss of metabolites. We optimized global metabolic profiling in FFPE tissue and identified metabolites distinguishing tumor from normal prostate tissue, and aggressive from non-aggressive prostate cancer. For optimization of metabolomics in FFPE tissues, we obtained matched frozen and FFPE tumor tissue from 62 prostate cancer cases who underwent radical prostatectomy (RP) at the University of North Carolina (UNC) hospital, of which 24 also had adjacent normal prostate tissue. To identify metabolites associated with tumor aggressiveness, we obtained matched tumor and normal FFPE tissue from 60 prostate cancer patients (Gleason ≥4+3, n=30; Gleason ≤3+4, n=30) who underwent RP participating in the UNC Health Registry/Cancer Survivorship Cohort. Following log transformation and imputation of missing values with the minimum observed value for each compound, Welch's two-sample t-test was used to identify biochemicals that differed significantly between groups. Random forest analysis evaluated predictive accuracy of metabolites for distinguishing tumor from normal prostate tissue. We identified 768 compounds of known identity in frozen and 119 in matched FFPE tissues. Therefore, only 15% of the metabolites detected in frozen samples were recovered from corresponding FFPE tissue, with 80% of these common to both FFPE and matched frozen tissues. We found a predictive accuracy of 78% and 67% for frozen and FFPE tissue, respectively, for distinguishing tumor from normal. Of 39 metabolites significantly altered between matched tumor and normal FFPE tissue, 47% belonged to the lipid class, and despite a greater number of significantly altered metabolites in frozen tissue (246), the proportion belonging to the lipid class was similar (50%). Citrate, integral to normal prostate metabolism, and citrulline, involved in nitric oxide synthesis, had significantly lower levels in aggressive versus non-aggressive tumors. Cell membrane phospholipids were found at significantly higher levels in aggressive tumors. Common patterns of altered metabolites in tumor vs. normal prostate were observed irrespective of tissue preservation method, despite loss of a large proportion of metabolites during the process of FFPE. As such, FFPE studies are feasible particularly when lipid metabolism is of interest as this class appears one of the best preserved in FFPE. This work will pave the way for incorporating metabolomics profiling of FFPE specimens into epidemiology and registry-based studies of prostate cancer. Citation Format: Sophia Rachael Halliday, Linnea T. Olsson, Alina Hamilton, Sivapriya Ramamoorthy, Jason Kitchen, Erin Kirk, Laura Farnan, Adrian Gerstel, Melissa A. Troester, Jannette T. Bensen, Sara E. Wobker, Emma Allott. Metabolomics profiling of formalin-fixed paraffin-embedded prostate tissues [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2347.

Background: Although statin use has been associated with reduced prostate cancer aggressiveness, the impact of race and patient characteristics on this association is not well understood. We examined the association between statin use and prostate cancer aggressiveness in Caucasians (CA) and African Americans (AA) and explored effect modification by health-seeking behaviors associated with statin use. Methods: Of 1,930 cases from The North Carolina-Louisiana Prostate Cancer Project, 344 (18%) were classified as aggressive based on clinical criteria. Utilizing nonaggressive cases as referent, logistic regression was used to examine the association between statin use and prostate cancer aggressiveness, overall and stratified by race. Smoking and prostate cancer screening were examined as effect modifiers of this association. Results: There was an inverse association between statin use and prostate cancer aggressiveness [OR, 0.74; 95% confidence interval (CI), 0.56–0.96], with comparable effect estimates in both races. Although not statistically significant, statin use was associated with reduced ORs for aggressive prostate cancer in never-screened men (OR, 0.79; 95% CI, 0.45–1.39), men screened at low/recommended frequency (≤once/year; OR, 0.66; 95% CI, 0.41–1.06), and men screened at high frequency (>once/year; OR, 0.78; 95% CI, 0.53–1.15). Inverse associations between statins and aggressive prostate cancer were strongest in never smokers (OR, 0.42; 95% CI, 0.25–0.72), attenuated in former smokers (OR, 0.84; 95% CI, 0.59–1.19), and absent in current smokers (OR, 1.36; 95% CI, 0.70–2.64). Conclusions: Statin use was associated with reduced prostate cancer aggressiveness in CA and AAs, with strongest inverse associations in nonsmokers. Impact: Health-seeking behaviors associated with statin use should be considered when examining the impact of statins on prostate cancer aggressiveness. Cancer Epidemiol Biomarkers Prev; 25(4); 670–7. ©2016 AACR.

Background Racial disparities in time-to-treatment exist among cancer patients, with patients of color being more likely to experience treatment delays. Such racial differences in treatment initiation are likely on the causal pathway to inequities in treatment outcomes. Emerging research has documented racial differences in financial burden, but little is known about the contribution of financial burden to disparities in treatment delays. In this study, we evaluated whether financial burden partly accounted for racial disparities in time to treatment initiation among a cohort of cancer survivors. Methods We used cross-sectional data of patients enrolled in the University of North Carolina Health Registry/Cancer Survivorship Cohort (HR/CSC) between 2010 and 2016. The sample for this study was limited to cancer patients and survivors who identified as non-Hispanic White or Black, received a diagnosis for breast, genitourinary, gastrointestinal, or head or neck cancer, and completed a questionnaire at least 30 days following their diagnosis (N=2,123). Time to treatment was measured in number of days from diagnosis to start of first course of treatment, ascertained from the medical record. Initial treatment was either surgery, chemotherapy, radiation, or hormonal therapy, depending on the clinical indication. Financial burden was assessed using the Patient Satisfaction Questionairre-18 on the self-reported satisfaction with the financial aspects of care (>3.5 is satisfied; Citation Format: Wendi Elkins, Olive Mbah, Jeannette T Benson, Laura Farnan, Neda Padilla, Sam Cykert, Bryce B Reeve, Giselle Corbie-Smith, Cleo A. Samuel. Impact of racial differences in financial burden on time to treatment [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D071.

Introduction: Epidemiologic data support a positive association between hypercholesterolemia and aggressive prostate cancer, and an inverse association between statin use and aggressive prostate cancer. Saturated fat intake is an important dietary determinant of serum cholesterol levels. However, epidemiologic evidence supporting a role for saturated fat in prostate cancer aggressiveness is mixed. We hypothesized that high saturated fat intake would be associated with increased prostate cancer aggressiveness, and that this association would be modified by statin use. Methods: Of 1,854 prostate cancer cases in the North Carolina-Louisiana Prostate Cancer Project (PCaP), 321 (17%) were classified as high aggressive based on clinical criteria. Saturated fat intake was adjusted for total fat intake using the residual method, and categorized into tertiles based on the distribution among all research subjects. Using low and intermediate aggressive cases as the reference group, logistic regression was used to examine the association between tertiles of saturated fat intake and prostate cancer aggressiveness, overall and stratified by race and by statin use. In addition to demographic and screening variables, energy-adjusted total fat intake and energy intake were included as covariates in our models. In secondary analysis, we examined associations for total fat, monounsaturated and polyunsaturated fatty acids (MUFA and PUFA, respectively), trans fat, and cholesterol intake. Results: High saturated fat intake was associated with an elevated odds ratio (OR) for aggressive prostate cancer (ORupper tertile (T3) vs. lower (T1) 1.44; 95% CI 1.06-1.96; p-trend = 0.020). The magnitude of this association was weaker in statin users (ORT3 vs. T1 1.10; 95% CI 0.63-1.91; p-trend = 0.790) compared to men not using statins (ORT3 vs. T1 1.63; 95% CI 1.11-2.37; p-trend = 0.015). There was a suggestion of a positive association between high cholesterol intake and aggressive prostate cancer among all men (ORT3 vs. T1 1.28; 95% CI 0.94-1.75; p-trend = 0.074), and this association was more pronounced in European Americans (ORT3 vs. T1 1.82; 95% CI 1.15-2.88; p-trend = 0.012). Elevated PUFA intake was inversely associated with prostate cancer aggressiveness (ORT3 vs. T1 0.66; 95% CI 0.48-0.90; p-trend = 0.009), with similar effect estimates in both races. There were no associations between trans fat or MUFA and prostate cancer aggressiveness. Conclusions: Elevated intake of saturated fat was positively associated, while high intake of PUFA was inversely associated, with aggressive prostate cancer. Weaker associations between saturated fat and prostate cancer aggressiveness in statin users suggest that the impact of saturated fat on serum cholesterol levels may be one potential mechanism by which saturated fat impacts prostate cancer aggressiveness. Citation Format: Emma H. Allott, Lenore Arab, L. Joseph Su, Laura Farnan, Elizabeth T.H. Fontham, James L. Mohler, Jeannette T. Bensen, Susan E. Steck. Saturated fat intake and prostate cancer aggressiveness: Results from the population-based North Carolina-Louisiana prostate cancer project. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1760.