Laura Farnan

How does health literacy affect quality of life among men with newly diagnosed clinically localized prostate cancer? Findings from the North Carolina-Louisiana Prostate Cancer Project (PCaP).

Health literacy deficits affect half of the US overall patient population, especially the elderly, and are linked to poor health outcomes among noncancer patients. Yet little is known about how health literacy affects cancer populations. The authors examined the relation between health‐related quality of life (HRQOL) and health literacy among men with prostate cancer.

Treatment decisional regret among men with prostate cancer: Racial differences and influential factors in the North Carolina Health Access and Prostate Cancer Treatment Project (HCaP-NC).

It has been demonstrated that treatment decisional regret affects quality of life in patients with prostate cancer (CaP); however, there are limited studies that identify factors associated with treatment decisional regret, particularly within a racially diverse patient population that has extended follow‐up.

Linear mixed effects models under inequality constraints with applications.

Constraints arise naturally in many scientific experiments/studies such as in, epidemiology, biology, toxicology, etc. and often researchers ignore such information when analyzing their data and use standard methods such as the analysis of variance (ANOVA). Such methods may not only result in a loss of power and efficiency in costs of experimentation but also may result poor interpretation of the data. In this paper we discuss constrained statistical inference in the context of linear mixed effects models that arise naturally in many applications, such as in repeated measurements designs, familial studies and others. We introduce a novel methodology that is broadly applicable for a variety of constraints on the parameters. Since in many applications sample sizes are small and/or the data are not necessarily normally distributed and furthermore error variances need not be homoscedastic (i.e. heterogeneity in the data) we use an empirical best linear unbiased predictor (EBLUP) type residual based bootstrap methodology for deriving critical values of the proposed test. Our simulation studies suggest that the proposed procedure maintains the desired nominal Type I error while competing well with other tests in terms of power. We illustrate the proposed methodology by re-analyzing a clinical trial data on blood mercury level. The methodology introduced in this paper can be easily extended to other settings such as nonlinear and generalized regression models.

Saturated fat intake and prostate cancer aggressiveness: results from the population-based North Carolina-Louisiana Prostate Cancer Project.

Background:Epidemiologic and laboratory evidence supports a role for cholesterol in prostate cancer (PC). Dietary saturated fat content impacts serum cholesterol levels. However, epidemiologic associations between saturated fat and PC aggressiveness are inconsistent. We hypothesized that high saturated fat intake would be associated with increased PC aggressiveness, and that statin use would modify this association.Methods:Of 1854 PC cases in the North Carolina-Louisiana PC Project, 321 (17%) were classified as high aggressive (Gleason sum ⩾8, PSA>20 ng ml−1, or Gleason sum ⩾7 and clinical stage T3-4) or low/intermediate aggressive (all other cases). Using low/intermediate aggressive cases as the referent group, we examined the association between tertiles of total fat-adjusted saturated fat intake and high aggressive PC using logistic regression, overall and stratified by race and statin use. We examined total fat-adjusted polyunsaturated and monounsaturated fatty acids (PUFA and MUFA, respectively), trans fat and cholesterol intake in secondary analysis.Results:High total fat-adjusted saturated fat intake was associated with an elevated odds ratio (OR) for aggressive PC (ORT3vsT1 1.51; 95% CI 1.10–2.06; P-trend=0.009), with an attenuated association in statin users (ORT3vsT1 1.16; 95% CI 0.67–2.01; P-trend=0.661) compared with non-users (ORT3vsT1 1.71; 95% CI 1.16–2.51; P-trend=0.053). High total fat-adjusted cholesterol intake was associated with aggressive PC in European Americans (ORT3vsT1 1.62; 95% CI 1.02–2.58; P-trend=0.056), but not African Americans (ORT3vsT1 0.92; 95% CI 0.60–1.42; P-trend=0.750). High total fat-adjusted PUFA was inversely associated with PC aggressiveness (ORT3vsT1 0.75; 95% CI 0.55–1.03), although this was not significant. No associations were found between total fat-adjusted MUFA or trans fat and PC aggressiveness.Conclusions:High total fat-adjusted saturated fat intake was associated with increased PC aggressiveness, with a suggestion of a stronger effect in men not using statins. The association between total fat-adjusted cholesterol intake and PC aggressiveness was most pronounced in European Americans.

Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina–Louisiana Prostate Cancer Project

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.

The Association of Diabetes and Obesity With Prostate Cancer Progression: HCaP‐NC

The role of race in modifying the association among diabetes, obesity, and prostate cancer (CaP) progression is not well studied. We evaluated diabetes and obesity in association with time to CaP progression in White Americans (Whites) and Black Americans (Blacks).

Statin use, high cholesterol and prostate cancer progression; results from HCaP-NC

Statin use is associated with lower advanced prostate cancer risk and reduced prostate cancer‐specific mortality, but prior studies were conducted mainly in white men. We examined the effect of statin use on risk of prostate cancer progression in a population‐based, minority‐enriched cohort.

Social Relationships, Inflammation, and Cancer Survival

Background: Social stressors, such as social relationship deficits, have been increasingly linked to chronic disease outcomes, including cancer. However, critical gaps exist in our understanding of the nature and strength of such links, as well as the underlying biological mechanisms relating social relationships to cancer progression and survival. Methods: Utilizing novel questionnaire and biomarker data from the UNC Health Registry/Cancer Survivorship Cohort, this study examines the associations between diverse measures of social support and mortality risk among individuals with cancer (N = 1,004). We further assess the role of multiple serum markers of inflammation, including high-sensitivity C-reactive protein (CRP), IL6, TNFα, and VEGF, as potential mediators in the social relationship–cancer link. Results: The findings revealed that ones appraisal of their social support was associated with cancer mortality, such that individuals reporting higher levels of social support satisfaction had lower mortality risk than individuals reporting lower levels of satisfaction. The amount of support received, on the other hand, was not predictive of cancer survival. We further found evidence that inflammatory processes may undergird the link between social support satisfaction and mortality among individuals with cancer, with individuals reporting higher levels of social support satisfaction having lower levels of CRP, IL6, and TNFα. Conclusions: These results provide new knowledge of the biosocial processes producing population disparities in cancer outcomes. Impact: Our study offers new insights for intervention efforts aimed at promoting social connectedness as a means for improving cancer survival. Cancer Epidemiol Biomarkers Prev; 27(5); 541–9. ©2018 AACR.

Mononuclear phagocyte system function and nanoparticle pharmacology in obese and normal weight ovarian and endometrial cancer patients

PurposeObesity may alter mononuclear phagocyte system (MPS) function and the pharmacology and efficacy of nanoparticles therapies, such as PEGylated liposomal doxorubicin (PLD). We aimed to evaluate the relationships between hormone and chemokine mediators of MPS function and the pharmacokinetic (PK) exposure of PLD in obese and normal weight patients with ovarian and endometrial cancer.MethodsHormone and chemokine mediators in obese and normal weight ovarian and endometrial cancer patients were measured. A separate pharmacology study was performed that evaluated the relationship between serum hormone concentrations, MPS function, and PK disposition of PLD in refractory ovarian cancer patients.ResultsUnivariate analysis revealed a significant relationship between serum estradiol and body mass index (OR 8.64, 95% CI 2.67–28.0, p < 0.001). Estrone and testosterone concentrations were positively correlated with MPS function (ρ = 0.57 and 0.53, p = 0.14 and 0.18, respectively) and inversely correlated with PLD PK exposure (ρ = − 0.75 and − 0.76, respectively, p = 0.02 for both).ConclusionsHigher MPS function resulting in reduced PLD exposure is a potential mechanism for reduced efficacy of PLD and other nanoparticles observed in obese patients with cancer. PK simulations suggest higher doses of PLD are required in obese patients to achieve similar exposures as standard dosing in normal weight patients.

The association of metformin use with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study

PurposeMetformin has been associated with a reduced incidence of prostate cancer and improved prostate cancer outcomes. However, whether race modifies the association between metformin use and prostate cancer aggressiveness remains uncertain. The association between metformin use and prostate cancer aggressiveness was examined separately in Black Americans (Blacks) and White Americans (Whites).MethodsThe study population consisted of 305 Black and 195 White research participants with incident prostate cancer and self-reported diabetes from the North Carolina–Louisiana Prostate Cancer Project. High-aggressive prostate cancer was defined using a composite measure of Gleason sum, prostate-specific antigen, and clinical stage. Multivariable logistic regression was used to assess the association between metformin use and high-aggressive prostate cancer at diagnosis, separately among Whites and Blacks, with adjustment for age, screening history, site, education, insurance, and body mass index.ResultsMetformin use was associated positively with high-aggressive prostate cancer in Blacks (OR 2.01; 95% CI 1.05, 3.83). By contrast, a weak inverse association between metformin use and high-aggressive prostate cancer was found in Whites (OR 0.80, 95% CI 0.34, 1.85).ConclusionsThe association between metformin use and prostate cancer aggressiveness may be modified by race.