North Carolina-Louisiana Prostate Cancer Project Research Articles

Cigarette smoking and prostate cancer aggressiveness among African and European American men.

Smoking is a modifiable lifestyle factor that has not been established as a prostate cancer risk factor, nor emphasized in prostate cancer prevention. Studies have shown that African American (AA) smokers have a poorer cancer prognosis than European Americans (EAs), while having a lower prevalence of heavy smoking. We examined the relationship between cigarette smoking and prostate cancer aggressiveness and assessed racial differences in smoking habits on the probability of high-aggressive prostate cancer. Using data from the North Carolina-Louisiana Prostate Cancer Project (n = 1,279), prostate cancer aggressiveness was defined as high or low based on Gleason scores, serum prostate-specific antigen levels, and tumor stage. Cigarette smoking was categorized as current, former, or never smokers. Multivariable logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Self-reported current (OR = 1.99; 95% CI 1.30-3.06) smoking was associated with high-aggressive prostate cancer relative to never smokers. When stratified by self-reported race, the odds of having high-aggressive cancer increased among AA current (OR = 3.58; 95% CI 2.04-6.28) and former smokers (OR = 2.21; 95% CI 1.38-3.53) compared to AA never smokers, but the odds were diminished among the EA stratum (Pself-reported race x smoking status = 0.003). Cigarette smoking is associated with prostate cancer aggressiveness, a relationship modulated by self-reported race. Future research is needed to investigate types of cigarettes smoked and metabolic differences that may be contributing to the racial disparities observed.

Abstract 2172: Associations between plant- and animal-based dietary patterns and aggressive prostate cancer in the North Carolina-Louisiana prostate cancer project (PCaP)

Abstract Objective: Results of studies examining the association between a plant-based diet or animal food intake and prostate cancer have been mixed. Few studies have focused on aggressive prostate cancer in a racially diverse population. We examined the association between healthy and unhealthy plant-based and animal-based diet scores and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project, a case-only study of Black and White men in the United States. Methods: Eighteen food groups were created and classified as healthy plant foods, unhealthy plant foods, or animal foods using dietary data collected from an interviewer-administered modified version of the National Cancer Institute Diet History Questionnaire among 909 Black and 991 White men with a histologically confirmed diagnosis of prostate cancer. High aggressive prostate cancer (n=332) was defined as Gleason sum ≥8; or PSA> 20ng/ml; or Gleason sum ≥7 and clinical stage T3-T4, and the comparison group was all other prostate cancer cases (n=1,568). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for high aggressive prostate cancer by tertiles of dietary pattern scores. Results: A decreased odds of aggressive prostate cancer was observed among men in the upper compared to the bottom tertile for healthy plant-based diet score (OR: 0.82, 95% CI: 0.58, 1.15) and unhealthy plant-based diet score (OR: 0.89, 95%CI: 0.63, 1.25) while an increased odds was observed comparing extreme tertiles of the animal-based diet score (OR: 1.17. 95% CI: 0.84-1.65) after adjustment for multiple covariates, though confidence intervals were imprecise and not statistically significant. Associations tended to be stronger among White men than among Black men; e.g., for the animal-based diet score, ORs (95% CIs) were 1.41 (0.86, 2.37) and 1.02 (0.63, 1.66) for White and Black men, respectively. Conclusions: Consuming a plant-based dietary pattern may be associated with lower odds of aggressive prostate cancer while an animal-based dietary pattern may be associated with higher odds, though associations were weak and not statistically significant. Keywords: Healthy plant-based diet, unhealthy plant-based diet, animal-based diet, aggressive prostate cancer, racial disparities Conflict of interest: None Funding: PCaP is carried out as a collaborative study supported by the Department of Defense contract DAMD 17-03-2-0052. This research was made possible in part by Grant Numbers R01-CA259415 from NIH-NCI and T32-GM081740 from NIH-NIGMS. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIGMS or NIH. Citation Format: Jessica Sainyo, Susan E. Steck, Longgang Zhao, L. Joseph Su, Lenore Arab, David Turner, Ebonee N. Butler, Jeannette T. Bensen, Elizabeth T.H. Fontham, James L. Mohler. Associations between plant- and animal-based dietary patterns and aggressive prostate cancer in the North Carolina-Louisiana prostate cancer project (PCaP) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2172.

Abstract B096: Cigarette smoking and prostate cancer aggressiveness among African and European American men

Abstract Background: Smoking is a modifiable lifestyle factor linked to prostate cancer (PCa) risk, but its association with PCa aggressiveness is unclear. Further, African-American men are likelier to smoke and be at risk for PCa. Therefore, we examined racial disparities in the association between cigarette smoking and PCa aggressiveness. Methods: Data for this study came from the North Carolina-Louisiana Prostate Cancer Project, a registry-based cohort study of incident PCa cases from 2004-2009 (n = 1,457). We defined PCa aggressiveness as high (Gleason score ≥ 8, Gleason score = 7 and TNM T3-T4, or prostate-specific antigen (PSA) score > 20 ng/mL) or low (Gleason score < 7, TNM T1-T2, and PSA < 10 ng/mL). We classified cigarette smoking as current, former, or never. Our analyses used multivariable logistic regression to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: One-third (35%) of PCa cases were high-aggressive. Half (48%) of the study sample was African-American. Current smoking, but not former smoking, was associated with high-aggressive PCa compared to never (OR = 2.2; 95% CI [1.5, 3.3]). African-Americans who currently smoked had higher odds of high-aggressive PCa than those who never smoked (OR = 3.2; 95% CI [1.9, 5.4]), as did those who formerly smoked (OR = 1.8; 95% CI [1.2, 2.3]). However, smoking did not significantly predict PCa aggressiveness in European-Americans. Conclusion: Cigarette smoking is associated with PCa aggressiveness, an association moderated by race. Future research should investigate the biological and social effects of smoking and PCa aggressiveness between racial groups. Citation Format: Edgar T. Ellis, Brian J. Fairman, Shelbie D. Stahr, L. Joseph Su, Ping-Ching Hsu. Cigarette smoking and prostate cancer aggressiveness among African and European American men [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B096.

Abstract P035: Associations between meat and fish intake and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP)

Abstract Objective: Results of studies examining the association between intake of meat or fish and prostate cancer have been mixed. However, few of the previous studies have included a racially diverse population or focused on aggressive prostate cancer. We aimed to examine the association between intake of meat and fish and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project, a case-only study of Black and White men in the United States. Methods: Meat and fish intakes in the year prior to diagnosis were estimated using an interviewer-administered modified version of the National Cancer Institute Diet History Questionnaire in 909 Black and 991 White men with a recent histologically confirmed diagnosis of prostate cancer. High aggressive prostate cancer (n=332) was defined as Gleason sum ≥8, or PSA> 20ng/ml, or Gleason sum ≥7 AND clinical stage T3-T4, and the comparison group was all other prostate cancer cases (n=1,568). Logistic regression was used to determine the odds ratio (OR) and 95% confidence intervals (95% CI) for high aggressive prostate cancer by tertile of meat and fish intake variables, with adjustment for age, energy intake, race, study site, education, family history of prostate cancer, prostate cancer screening history, Charlson comorbidity index, NSAIDs use, smoking status, alcohol intake, and intake of vegetables, fruits, and milk. Results: We observed increased odds of aggressive prostate cancer among men in the second tertile compared to the first tertile for total red meat (OR:1.23. 95% CI: 0.91 – 1.68) and unprocessed red meat (OR:1.30. 95% CI: 0.96 – 1.76), though confidence intervals were imprecise and associations in the top tertile were weaker. For processed meat, a non-statistically significant increased odds of aggressive prostate cancer was observed among men in the third tertile compared to the first tertile (OR:1.27. 95% CI: 0.91 – 1.78). ORs for higher intake of fish and poultry were in the inverse direction but were weak and not statistically significant. Conclusions: In this racially diverse case-only study, we observed weak positive associations between red and processed meat and aggressive prostate cancer, and little evidence of an association with fish or poultry intake. While high temperature cooking and charring of meat is known to increase carcinogen formation, one limitation of our study was the lack of information on cooking methods or doneness of the meat consumed. Additional research is warranted among racially diverse populations that considers cooking methods and doneness preferences. Citation Format: Jessica Sainyo, Susan E. Steck, L. Joseph Su, Lenore Arab, Jeannette T. Bensen, Elizabeth T.H. Fontham, James L. Mohler. Associations between meat and fish intake and aggressive prostate cancer in the North Carolina-Louisiana Prostate Cancer Project (PCaP). [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P035.

Prostate cancer aggressiveness and financial toxicity among prostate cancer patients.

Financial toxicity (FT) is a growing concern among cancer survivors that adversely affects the quality of life and survival. Individuals diagnosed with aggressive cancers are often at a greater risk of experiencing FT. The objectives of this study were to estimate FT among prostate cancer (PCa) survivors after 10-15 years of diagnosis, assess the relationship between PCa aggressiveness at diagnosis and FT, and examine whether current cancer treatment status mediates the relationship between PCa aggressiveness and FT. PCa patients enrolled in the North Carolina-Louisiana Prostate Cancer Project (PCaP) were recontacted for long-term follow-up. The prevalence of FT in the PCaP cohort was estimated. FT was estimated using the COmprehensive Score for Financial Toxicity, a validated measure of FT. The direct effect of PCa aggressiveness and an indirect effect through current cancer treatment on FT was examined using causal mediation analysis. More than one-third of PCa patients reported experiencing FT. PCa aggressiveness was significantly independently associated with high FT; high aggressive PCa at diagnosis had more than twice the risk of experiencing FT than those with low or intermediate aggressive PCa (adjusted oddsratio[aOR] = 2.13, 95% CI = 1.14-3.96). The proportion of the effect of PCa aggressiveness on FT, mediated by treatment status, was 10%, however, the adjusted odds ratio did not indicate significant evidence of mediation by treatment status (aOR = 1.05, 95% CI = 0.95-1.20). Aggressive PCa was associated with high FT. Future studies should collect more information about the characteristics of men with high FT and identify additional risk factors of FT.

Using health insurance claims data to assess long-term disease progression in a prostate cancer cohort.

Long-term population-based cohort studies of men diagnosed with prostate cancer are limited. However, adverse outcomes can occur many years after treatment. Herein, we aim to assess the utility of using claims data to identify prostate cancer progression 10-15 years after diagnosis. The study population was derived from the North Carolina-Louisiana Prostate Cancer Project (PCaP). PCaP-North Carolina (NC) included 1031 men diagnosed with prostate cancer from 2004 to 2009.An initial follow-up with a survey and manual medical record abstraction occurred from 2008 to 2011 (Follow-up 1). Herein, we extended this follow-up with linkage to healthcare claims data from North Carolina (2011-2017) and a second, supplementary 10-year follow-up survey (2018-2020) (Follow-up 2). Vital statistics data also were utilized. Long-term oncological progression was determined using these data sources in combination with expert clinical input. Among the 1031 baseline PCaP-NC participants, 652 were linked to medical claims. Forty-two percent of the men had insurance coverage for the entire 72 months of follow-up. In addition, 275 baseline participants completed the supplementary 10-year follow-up survey. Using all sources of follow-up data, we identified a progression event in 259 of 1031 (25%) men with more than 10 years of follow-up data after diagnosis. Understanding long-term clinical outcomes is essential for improving the lives of prostate cancer survivors. However, access and utility of long-term clinical outcomes with claims alone remain a challenge due to individualized agreements required with each insurer for data access, lack of detailed clinical information, and gaps in insurance coverage. We were able to utilize claims data to determine long-term progression due to several unique advantages that included the availability of detailed baseline clinical characteristics and treatments, detailed manually abstracted clinical data at 5 years of follow-up, vital statistics data, and a supplementary 10-year follow-up survey.

Recreational and occupational physical activity in relation to prostate cancer aggressiveness: the North Carolina-Louisiana Prostate Cancer Project (PCaP).

To examine associations between recreational and occupational physical activity and prostate cancer aggressiveness in a population-based, case-only, incident prostate cancer study. Data were analyzed from the cross-sectional North Carolina-Louisiana Prostate Cancer Project of African-American (n = 1,023) and European-American (n = 1,079) men newly diagnosed with prostate cancer (CaP). High-aggressive CaP was defined as Gleason sum ≥ 8, or prostate-specific antigen > 20ng/ml, or Gleason sum ≥ 7 and clinical stage T3-T4. Metabolic equivalent tasks (MET) were estimated from self-reported recreational physical activity in the year prior to diagnosis assessed retrospectively via a validated questionnaire and from occupational physical activity based on job titles. Associations between physical activity variables and high-aggressive prostate cancer were estimated using logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple confounders. There was suggestive evidence that walking for 75-150min/week for exercise is associated with lower odds of high-aggressive prostate cancer compared to no walking (OR = 0.69, 95% CI 0.47-1.01). Physical activity at the current job was associated with 24% lower odds of high-aggressive prostate cancer (highest vs. lowest tertile OR = 0.76, 95% CI 0.56-1.04). However, total MET-h/week of recreational physical activity and accumulation of high-level physical activity at the longest-held job were not associated with high-aggressive prostate cancer. Results did not vary by race. The odds of high-aggressive prostate cancer were lower among men who walk for exercise and those engaged in occupations with high activity levels.

Neighborhood deprivation and risk of mortality among men with prostate cancer: Findings from a long-term follow-up study.

BackgroundThe overall survival rate of prostate cancer (PCa) has improved over the past decades. However, huge socioeconomic and racial disparities in overall and prostate cancer‐specific mortality exist. The neighborhood‐level factors including socioeconomic disadvantage and lack of access to care may contribute to disparities in cancer mortality. This study examines the impact of neighborhood deprivation on mortality among PCa survivors.MethodsNorth Carolina–Louisiana Prostate Cancer Project (PCaP) data were used. A total of 2113 men, 1046 AA and 1067 EA, with PCa were included in the analysis. Neighborhood deprivation was measured by the Area Deprivation Index (ADI) at the census block group level using data from the US Census Bureau. Quintiles of ADI were created. Cox proportional hazards and competing risk models with mixed effects were performed to estimate the effect of neighborhood deprivation on all‐cause and PCa‐specific mortality adjusted for age, race, study site, insurance status, and comorbidities.ResultsParticipants living in the most deprived neighborhoods had an increased risk for all‐cause mortality (quintiles 4 + 5: adjusted hazard ratio [aHR] = 1.51, 95% confidence interval [CI] = 1.16–1.96) compared to those in the least deprived (quintile 1) neighborhoods. The risk of prostate cancer‐specific mortality was also higher among those living in the deprived neighborhoods (quintiles 4 + 5: aHR = 1.90, 95% CI = 1.10–3.50) than those in the least deprived neighborhood.ConclusionsThe findings suggest neighborhood‐level resources or health interventions are essential to improve survival among men with PCa. Additional research should focus on the mechanisms of how the neighborhood environment affects mortality.

Differential Associations of SLCO Transporters with Prostate Cancer Aggressiveness between African Americans and European Americans.

Androgen receptor signaling is crucial to prostate cancer aggressiveness. Members of the solute carrier family of the organic anion transporting peptides (SLCO) are potential regulators of androgen availability in prostate tissue. It remains unknown whether genetic variations in SLCOs contribute to the differences in prostate cancer aggressiveness in African Americans (AA) and European Americans (EA). SNPs in 11 SLCO members were selected, with addition of 139 potentially functional SNPs and 128 ancestry informative markers. A total of 1,045 SNPs were genotyped and analyzed in 993 AAs and 1,057 EAs from the North Carolina-Louisiana Prostate Cancer Project. Expression and cellular localization of SLCOs were examined using qRT-PCR, IHC, and in situ RNA hybridization in independent sets of prostate cancer cases. Significant associations with prostate cancer characteristics were found for SNPs in SLCO2A1 and SLCO5A1. The associations differed by race (P interaction < 0.05). SNPs in SLCO2A1 were associated with reduced tumor aggressiveness and low Gleason score in AAs; whereas, SNPs in SLCO5A1 were associated with high clinical stage in EAs. In prostate tissue, SLCO2A1 and SLCO5A1 were the most expressed SLCOs at the mRNA level and were expressed predominantly in prostate endothelial and epithelial cells at the protein level, respectively. SLCO2A1 and SLCO5A1 play important but different roles in prostate cancer aggressiveness in AAs versus EAs. The finding calls for consideration of racial differences in biomarker studies of prostate cancer and for investigations on functions of SLCO2A1 and SLCO5A1 in prostate cancer.

Abstract PO-201: Smoking as a risk factor for the aggressive prostate cancer for African-American men from the North Carolina–Louisiana Prostate Cancer Project (PCaP)

Abstract Background. Significant racial disparities exist in PCa, with the incidence in African- Americans (AAs) being 50% higher than European Americans (EAs) and PCa mortality rates in AAs being more than two-fold higher. However, the disparity cannot be explained by screening, access to treatment, and genetics can only partially explain the disparity that does little to confer actionable clinical relevance. Currently, only 3 definitive risk factors for PCa have been identified: age, race, and family history of PCa. Smoking has not been an established risk factor for prostate cancer (PCa), and has not been emphasized in PCa prevention. However, recent studies have shown increasing evidence that there is a higher risk of biochemical recurrence, PCa mortality, and metastasis among current smokers, presenting an urgent need in re- evaluating the association between smoking and aggressive PCa. This study aimed to determine whether smoking increase the likelihood of developing a more aggressive prostate cancer. Methods. The study used data from the North Carolina–Louisiana Prostate Cancer Project (PCaP), which is a population-based study of incident PCa conducted between years 2004-2009 in 2 southern states where significant racial disparities in PCa are observed. Because PCa is over diagnosed and most PCa is not clinically relevant, this study will include only subjects with high (Gleason score ≥ 8; PSA &amp;gt; 20 ng/mL; Gleason score = 7 and stage T3–T4) or low (Gleason score &amp;lt; 7 and stage T1–T2 and PSA &amp;lt;10 ng/mL) PCa aggressiveness. 1,497 participants were included in the analysis. Chi square and t-tests were used for the variables of interest and possible confounders, and multivariable logistic regression models were used for the odds ratio estimate. Results. There were 44.9% AAs and 55.1% EAs in the study. AA participants were significantly younger (mean=61.8, SD=7.9) compared with EAs (mean=64.0, SD=7.9), with lower education levels, shorter smoking cessation period, less screening tests in the past, less cigarettes per day, and higher Gleason sum. From the analysis, more AAs (57.6%) and those who were current smokers (22.7%) were diagnosed with high aggressive PCa. Current smokers had a 2.4 times- higher risk of high aggressive PCa (unadjusted OR=2.42, adjusted OR=2.39); when stratified by race, the risk diminished for EAs (OR=1.30) but increased for AAs (OR=3.36). Conclusion. Our study shows increased risk of aggressive PCa for current smokers, especially among AAs. Previous study had shown that self-reported cigarettes per day predicts smoke intake more poorly in AAs than in EAs. Thus, there is an urgent need in validated research using biomarkers to confirm the relationship of smoking and aggressive PCa, since cigarette smoking is preventable but have not been emphasized in PCa prevention. Citation Format: Ping-Ching Hsu, Shelbie Stahr, Christopher Brazeal, Elizabeth H. Fontham, L. Joseph Su. Smoking as a risk factor for the aggressive prostate cancer for African-American men from the North Carolina–Louisiana Prostate Cancer Project (PCaP) [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-201.

Abstract PR14: Dietary folate and prostate cancer tumor aggressiveness differences between African Americans and European Americans

Abstract Introduction: Folate is a water-soluble B vitamin, which is involved in DNA synthesis and repair and in regulation of gene expression through DNA methylation as a methyl donor. Despite the confirmed beneficial effect on the prevention of neural tube defect, concerns have been raised on high intakes of folate and its synthetic form, folic acid, may promote carcinogenesis or cancer progression. African American (AA) males tend to have a more aggressive prostate cancer tumor diagnosis compared to European American (EA) males. Objective: This aim of this study is to examine the association between folic acid intake in the year prior to PCa diagnosis among AAs and EAs. Using a population-based case-only study, an examination of folic acid was conducted to evaluate the effects of dietary folate on prostate cancer aggressiveness. Methods: Data from the North Carolina-Louisiana Prostate Cancer Project (PCaP) questionnaire were used to evaluate 1,497 participants (AA n = 722 and EA n = 775) with a low or high aggressiveness prostate cancer to assess dietary folate intake one year prior to PCa diagnosis using the National Cancer Institute Dietary History Questionnaire. High-aggressive disease was defined as Gleason sum ≥8, or prostate-specific antigen (PSA) &amp;gt;20 ng/mL, or Gleason score ≥7 and clinical stage T3-T4, while low-aggressive disease was defined as Gleason sum &amp;lt;7 and stage T1—T2 and PSA &amp;lt;10 ng/mL. All four variables for dietary folate (natural folate, synthetic folate, folate, and dietary folates) were examined. Multivariate logistic regression was used to assess dietary folate and prostate cancer aggressiveness. Confounding variables considered for this analysis include age, BMI, total energy (kcal), education level, and first-degree family history of PCa. Additionally, dietary folate was categorized into tertiles. Models were stratified by race and the dose-response relationship was evaluated. Results: Folate intakes, regardless natural folate (mean = 354.5 vs 304.1), synthetic folate (176.3 vs 157.5), or total dietary folate equivalent (654.0 vs 571.5), were higher among AA than EA, respectively. Based on the tertile categorization, the highest dietary folate was significantly associated with high-aggressive prostate cancer when compared to the lowest intake group among AA and EA combined (odds ratio (OR) = 1.41, 95% confidence interval (CI) = 1.04 – 1.90) after adjusted for confounders. Stratified model by race showed that there is an increased trend in PCa aggressiveness and increased folate intake (2nd tertile OR = 1.03, 95%CI = 0.67 – 1.56; 3rd tertile OR = 1.41, CI = 1.11 – 2.48), p-value for trend = 0.01. The association was not observed among EA. The trend is very similar regardless of natural or synthetic folate. Conclusion: It appeared that AA with high folic acid intake had a greater chance of being diagnosed with high-aggressiveness PCa, while the association was not observed among EA. The finding suggests that the metabolism of folate may be different between AA and EA, possibly due to genetic polymorphisms. This abstract is also being presented as Poster C034. Citation Format: Daniela Ramirez Aguilar, Susan E Steck, Hui-Yi Lin, LJ Su. Dietary folate and prostate cancer tumor aggressiveness differences between African Americans and European Americans [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 PR14.

Prevalence and predictors of probable depression in prostate cancer survivors.

The early diagnosis and treatment of depression are cancer care priorities. These priorities are critical for prostate cancer survivors because men rarely seek mental health care. However, little is known about the epidemiology of depression in this patient population. The goal of this study was to describe the prevalence and predictors of probable depression in prostate cancer survivors. The data were from a population-based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 in the North Carolina-Louisiana Prostate Cancer Project (n=1031) and were prospectively followed annually from 2008 to 2011 in the Health Care Access and Prostate Cancer Treatment in North Carolina study (n=805). Generalized estimating equations were used to evaluate an indicator of probable depression (Short Form 12 mental composite score ≤48.9; measured at enrollment and during the annual follow-up) as a function of individual-level characteristics within the longitudinal data set. The prevalence of probable depression fell from 38% in the year of the cancer diagnosis to 20% 6 to 7years later. Risk factors for probable depression throughout the study were African American race, unemployment, low annual income, younger age, recency of cancer diagnosis, past depression, comorbidities, treatment decisional regret, and nonadherence to exercise recommendations. Depression is a major challenge for prostate cancer survivors, particularly in the first 5years after the cancer diagnosis. To the authors' knowledge, this is the first study to demonstrate an association between treatment decisional regret and probable depression.

Patterns and predictors of self-reported clinical diagnosis and treatment for depression in prostate cancer survivors.

BackgroundAppropriate depression care is a cancer‐care priority. However, many cancer survivors live with undiagnosed and untreated depression. Prostate cancer survivors may be particularly vulnerable, but little is known about their access to depression care. The goal of this study was to describe patterns and predictors of clinical diagnosis and treatment of depression in prostate cancer survivors.MethodsGeneralized estimating equations were used to evaluate indicators of self‐reported clinical diagnosis and treatment depression as a function of individual‐level characteristics within a longitudinal dataset. The data were from a population‐based cohort of North Carolinian prostate cancer survivors who were enrolled from 2004 to 2007 on the North Carolina‐Louisiana Prostate Cancer Project (N = 1,031), and prospectively followed annually from 2008 to 2011 on the Health Care Access and Prostate Cancer Treatment in North Carolina (N = 805).ResultsThe average rate of self‐reported clinical diagnosis of depression was 44% (95% CI: 39%‐49%), which declined from 60% to 40% between prostate cancer diagnosis and 5‐7 years later. Factors associated with lower odds of self‐reported clinical diagnosis of depression include African‐American race, employment, age at enrollment, low education, infrequent primary care visits, and living with a prostate cancer diagnosis for more than 2 years. The average rate of self‐reported depression treatment was 62% (95% CI: 55%‐69%). Factors associated with lower odds of self‐reported depression treatment included employment and living with a prostate cancer diagnosis for 2 or more years.ConclusionProstate cancer survivors experience barriers when in need of depression care.

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

Metformin 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). The 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. Metformin 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). The association between metformin use and prostate cancer aggressiveness may be modified by race.

Dietary patterns based on the Mediterranean diet and DASH diet are inversely associated with high aggressive prostate cancer in PCaP

BackgroundSeveral foods and nutrients have been linked to the development of prostate cancer, but the association between healthy dietary patterns and prostate cancer aggressiveness is less studied. The aim of this study was to evaluate the relationship between the Mediterranean diet (MED) and Dietary Approaches to Stop Hypertension (DASH) diet scores and prostate cancer aggressiveness by race. MethodsData from the population-based, case-only North Carolina–Louisiana Prostate Cancer Project (PCaP) were used to examine the association between diet quality, measured by MED and DASH scores, and prostate cancer aggressiveness in 1899 African American (AA) and European American (EA) research subjects. Dietary intake was assessed using a modified National Cancer Institute Diet History Questionnaire. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for high versus low-intermediate aggressive prostate cancer. ResultsHigher MED scores were inversely associated with high aggressive prostate cancer overall (OR: 0.66; 95% CI: 0.46, 0.95 for high versus low scores); results were similar for AA and EA men. A weaker inverse association between DASH scores and prostate cancer aggressiveness was found (OR: 0.76; 95% CI: 0.55, 1.06). ConclusionsHigher diet quality, as represented by a Mediterranean-style diet or DASH diet, may reduce the odds of high aggressive prostate cancer.

Use of non-steroidal anti-inflammatory drugs and prostate cancer aggressiveness among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCAP)

Introduction In the context of a possible role of chronic inflammation in cancer risk, Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have received attention for their potential as chemopreventive drugs against cancer. Therefore, we investigated the role of NSAIDs use in relation to prostate cancer aggressiveness among African and European Americans using data from the North Carolina-Louisiana Prostate Cancer Project (PCAP). Methods PCaP is a population-based, case-only study of incident prostate cancer in two southern U.S states. Overall, 2258 men (1130 African Americans and 1128 European Americans) newly diagnosed with prostate cancer between 2004 and 2009, aged 40 to 79 years and residing in North Carolina or Louisiana at diagnosis have been visited in their home by trained nurses who administered a standardized questionnaire on background characteristics, occupation, comorbid conditions and medications, health care access, prostate cancer diagnosis and screening history, diet, vitamins and supplements use and physical activity. Nurses also collected information of historic (five years prior to prostate cancer diagnosis) and current (within the two weeks prior to the in-home visit) use of NSAIDS. Historic NSAIDs use was self-reported by the patient (frequency, duration and product name) and current use was obtained by a review of all medications and their bottles used in the two weeks prior to the in-home visit (product name and concentration). Cancer aggressiveness was achieved using Gleason Sum abstracted from medical records. Aggressive prostate cancer was defined by Gleason sum > 7 or Gleason sum = 7 when the two most frequently represented grades in the tumor analyzed were 4 + 3. Multivariate unconditional logistic regression models were used to estimate Odds Ratios (ORs) and their 95% confidence interval (95% CI). Analyzes were performed in all men as well as stratified by race and age ( Results NSAID use 5 years prior to diagnosis was not associated with aggressive prostate cancer (OR = 0.97, 95% CI: 0.77–1.21), whether among African Americans or European Americans. There was no dose-response relationship either with frequency or duration. After stratification on age, we observed an inverse association between NSAID use and aggressive prostate cancer among men under the age of 60 (OR = 0.62, 95%CI: 0.40–0.94), with a more pronounced association for at least 10 years of use (OR = 0.37, 95% CI: 0.15–0.92) and a use of more than 1 per day (OR = 0.42, 95% CI: 0.22–0.83). A chronic use, defined by a use during at least 5 years prior to diagnosis and a use at time of diagnosis, was not associated with aggressive prostate cancer overall (OR = 0.84, 95% CI: 0.64–1.11) or in African Americans (OR = 1.11, 95% CI: 0.76–1.64), but was inversely associated with aggressive prostate cancer in European Americans (OR = 0.64, 95% CI: 0.43–0.96). Interestingly, an inverse association was observed overall for men who used NSAIDs preferentially acting on COX2 (OR = 0.39, 95% CI: 0.19–0.82), specifically observed in European Americans (OR = 0.33, 95% CI: 0.11–0.99) even though results are based on small numbers. Conclusions Our results suggest an inverse association between a chronic use of NSAID and prostate cancer aggressiveness, particularly in men who used preferential COX2 inhibitors, and in European Americans. Those results need further investigations to be confirmed.

Calcium, magnesium, and whole-milk intakes and high-aggressive prostate cancer in the North Carolina–Louisiana Prostate Cancer Project (PCaP)

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. 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. 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. 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. 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.

The association of diabetes and obesity with prostate cancer aggressiveness among Black Americans and White Americans in a population-based study.

Few studies have investigated the role of race in the association of diabetes and obesity with prostate cancer aggressiveness. Here we evaluate the independent association between diabetes and obesity with prostate cancer aggressiveness in White Americans and Black Americans. Our cross-sectional, case-only study consisted of 1,058 White Americans and 991 Black Americans from the North Carolina-Louisiana Prostate Cancer (PCaP) project. Diabetes status was determined by self-report. Obesity was determined using body mass index and calculated based on anthropometric measurements. High aggressive prostate cancer was defined as Gleason sum ≥8, or prostate-specific antigen >20ng/ml, or Gleason sum=7 and clinical stage cT3-cT4. The association between diabetes and obesity with high aggressive prostate cancer at diagnosis was evaluated using multivariable logistic regression and adjusted for potential confounders. Diabetes was not associated with high aggressive prostate cancer in the overall sample (OR 1.04; 95% CI 0.79, 1.37), White Americans (OR 1.00; 95% CI 0.65, 1.57) or Black Americans (OR 1.07; 95% CI 0.75, 1.53). Obesity, independent of diabetes, was positively associated with high aggressive prostate cancer in White Americans (OR 1.98; 95% CI 1.14, 3.43), but not in the overall sample (OR 1.37; 95% CI 0.99, 1.92) or Black Americans (OR 1.09; 95% CI 0.71, 1.67). Diabetes was not associated with prostate cancer aggressiveness, overall, or in either race group. Obesity, independent of diabetes, was associated with high aggressive prostate cancer only in White Americans.

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

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. 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. 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. 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.

Abstract 1760: Saturated fat intake and prostate cancer aggressiveness: Results from the population-based North Carolina-Louisiana prostate cancer project

Abstract 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.