Differences In Incidence Of Prostate Cancer Research Articles

Genetic susceptibility to prostate cancer in Taiwan: A genome-wide association study.

We conducted the first genome-wide association study (GWAS) of prostate cancer (PCa) in Taiwan with 1844 cases and 80,709 controls. Thirteen independent single-nucleotide polymorphisms (SNPs) reached genome-wide significance (p < 5 × 10-8 ). Among these, three were distinct from previously identified loci: rs76072851 in CORO2B gene (15q23), odds ratio (OR) = 1.54, 95% confidence interval (CI), 1.36-1.76, p = 5.30 × 10-11 ; rs7837051, near two long noncoding RNA (lncRNA) genes, PRNCR1 and PCAT2 (8q24.21), OR = 1.41 (95% CI, 1.31-1.51), p = 8.77 × 10-21 ; and rs56339048, near an lncRNA gene, CASC8 (8q24.21), OR = 1.25 (95% CI, 1.16-1.35), p = 2.14 × 10-8 . We refined the lead SNPs for two previously identified SNPs in Taiwanese: rs13255059 (near CASC8), p = 9.02 × 10-43 , and rs1456315 (inside PRNCR1), p = 4.33 × 10-42 . We confirmed 35 out of 49 GWAS-identified East Asian PCa susceptibility SNPs. In addition, we identified twoSNPs more specific to Taiwanese than East Asians: rs34295433 in LAMC1 (1q25.3) and rs6853490 in PDLIM5 (4q22.3). A weighted genetic risk score (GRS) was developed using the 40 validated SNPs and the area under the receiver-operating characteristiccurvefor the GRS to predict PCa was 0.67 (95% CI, 0.63-0.71). These identified SNPs provide valuable insights into the molecular mechanisms of prostate carcinogenesis in Taiwan and underscore the significant role of genetic susceptibility in regional differences in PCa incidence.

Abstract B081: Biological and neighborhood-level social drivers of aggressive prostate disease among Black and White men

Abstract Introduction and study purpose: Prostate cancer (PCa) is the leading type of newly diagnosed cancer and second leading cause of cancer death in American men. Significant racial differences in PCa incidence and mortality have been long-reported in the U.S., with Black men demonstrating a disproportionately higher burden of disease compared to White men. However, some studies conducted in equal access health care settings have revealed equivalent PCa outcomes for White and Black men. Identification of early predictors of prostate disease aggressiveness is essential to avoid over-treatment of clinically favorably disease that is unlikely to progress. This study examines the independent and joint roles of biological and social determinants of health (SDOHs) in predicting prostate disease aggressiveness in a racially diverse cohort of men undergoing biopsy for suspicion of PCa. Methodology: A retrospective cohort study was conducted at the University Hospitals (UH) Seidman Cancer Center in Cleveland, Ohio for the period January 1, 2005-December 2022. A retrospective chart review was conducted to identify eligible men, including White and Black men undergoing transrectal ultrasound-guided biopsy whose biopsy results included the following 3 groups: (i) negative biopsy with a history of 1+ negative biopsy (-ies) and no history of prostate cancer; (ii) biopsy-detected PCa of Gleason sum 6; and (iii) biopsy-detected PCa with metastasis (-es) at initial cancer detection. Detailed clinical and biological specimen data were abstracted and quantitative proteomics analysis of biopsy tissues using mass spectrometry has been conducted at the Pacific Northwest National Laboratory (PNNL). Residential addresses were used to link each man to his census-block group Area Deprivation Index (ADI) score, as a metric of SDoHs. Students t-tests, ANOVAs and Pearson correlation analysis have been performed on the first 60 eligible subjects. Results: This study has generated the entire proteome on the first 60 eligible subjects (“Discovery cohort”) and SDoH metrics have been linked to the first 284 of 300 eligible subjects. Among the first 60 subjects, there was strong separation in proteome profiles for metastatic PCa cases but little separation of Gleason 6 and biopsy negative subjects was observed. Interesting, among the proteins that showed significant correlation with clinical group, few proteins were also significant correlated with subject race. However, several oproteins were strongly associated with SDoHs. Conclusions: Identifying new markers of cancer aggressiveness within and across race has the potential to tailor disease management and identify patients who are likely to benefit from earlier, timely treatment interventions, which will ultimately improve prostate cancer outcomes and quality of life. Upon completion of targeted proteomic analyses, we will perform multi-level modeling to predict prostate disease aggressiveness as a function of protein biomarker candidates in combination with census block group-level SDOHs. Citation Format: Jennifer Cullen, Tao Liu, Karin Rodland, Ranjini Ghosh, Anood Alfahmy, Julia Payne, Sweta Balaji, Holly Hartman, Lee Ponsky, Jonathan Shoag, Gregory MacLennan. Biological and neighborhood-level social drivers of aggressive prostate disease among Black and White 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 B081.

Abstract C088: Biological and neighborhood-level social determinants of prostate disease aggressiveness among Black and White men undergoing prostate biopsy

Abstract Introduction and study purpose: Prostate cancer (PCa) is the leading type of newly diagnosed cancer and second leading cause of cancer death in American men. Significant racial differences in PCa incidence and mortality have been long-reported in the U.S., with Black men demonstrating a disproportionately higher burden of disease compared to White men. Though some studies conducted in equal access health care settings have revealed equivalent PCa characteristics at diagnosis and comparable PCa outcomes for White and Black men. Identification of early predictors of prostate disease aggressiveness is essential to avoid over-treatment of clinically favorably disease that is unlikely to progress. This study examines the independent and joint roles of biological and social determinants of health (SDOHs) in predicting prostate disease aggressiveness in a racially diverse cohort of men undergoing biopsy for suspicion of PCa. Methodology: A retrospective cohort study was conducted at the University Hospitals Seidman Cancer Center in Cleveland, Ohio for the period January 1, 2005-May 2022. A retrospective chart review was conducted to identify eligible men, including White and Black men undergoing transrectal ultrasound-guided biopsy whose biopsy results included the following 3 groups: (i) negative biopsy with a history of 1+ negative biopsy (-ies) and no history of prostate cancer; (ii) biopsy-detected PCa of Gleason sum 6; and (iii) biopsy-detected PCa with metastases at initial cancer detection. Detailed clinical and biological specimen data were abstracted during retrospective chart review, and quantitative proteomics analysis of biopsy tissues is ongoing, using mass spectrometry, at the Pacific Northwest National Laboratory (PNNL). Multi-level modeling will be conducted to predict prostate disease aggressiveness as a function of protein biomarker candidates in combination with census block group-level SDOHs. Results: This study has achieved its initial goal of assembling a study cohort of 300 eligible men with available biopsy tissue, necessary clinical information, and full street address for assigning census regions. To date, proteomics data have been generated on the first 60 men (“Discovery cohort”) and SDOHs metrics have been linked to the first 180 men. Proteomic profiles and SDOH data will be examined jointly with SDOHs to predict patient clinical phenotype (i.e., metastatic, biopsy Gleason 6, biopsy negative). Conclusions: Identifying new markers of cancer aggressiveness within and across race has the potential to tailor disease management, and identify patients who are likely to benefit from earlier, timely treatment interventions, which will ultimately improve prostate cancer outcomes and quality of life. Predictive modeling that jointly considers biological determinants of cancer disparities in conjunction with neighborhood-level social factors have the potential to elucidate who can be safely spared repeat biopsies, as well as how to optimize cancer care. Citation Format: Jennifer Cullen, Tao Liu, Karin Rodland, Ranjini Ghosh, Anood Alfamy, Julia Payne, Kirsten Eom, Sweta Balaji, Nicole Diaz, Holly Hartman, Annie Liang Zhang, Daniel Spratt, Jonathan Shoag, Erika Trapl, Lee Ponsky, Gregory MacLennan. Biological and neighborhood-level social determinants of prostate disease aggressiveness among Black and White men undergoing prostate biopsy [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr C088.

Racial Disparities in Prostate Cancer: Evaluation of Diet, Lifestyle, Family History, and Screening Patterns.

Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African-American men had an 80% higher prostate cancer risk than White men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary analysis of racial differences in prostate cancer incidence and mortality in HPFS. For 47,679 men, we estimated HRs and 95% confidence intervals (CI) for the association between race and risk of prostate cancer through 2016 using Cox proportional hazards regression. Multivariable models (mHR) were adjusted for lifestyle, diet, family history, and PSA screening collected on biennial questionnaires. 6,909 prostate cancer cases were diagnosed in White, 89 in African-American, and 90 in Asian-American men. African-Americans had higher prostate cancer incidence (mHR = 1.31; 95% CI, 1.06-1.62) and mortality (mHR = 1.67; 95% CI, 1.00-2.78), and lower PSA screening prevalence than White men. The excess risk was greater in the pre-PSA screening era (HR = 1.68; 95% CI, 1.14-2.48) than the PSA screening era (HR = 1.20; 95% CI, 0.93-1.56). Asian-Americans had lower prostate cancer risk (mHR = 0.74; 95% CI, 0.60-0.92), but similar risk of fatal disease compared with white men. Racial differences in prostate cancer incidence and mortality in HPFS are not fully explained by differences in lifestyle, diet, family history, or PSA screening. Additional research is necessary to address the disproportionately higher rates of prostate cancer in African-American men.

Why do African-American men face higher risks for lethal prostate cancer?

Purpose of reviewAfrican–American men in the USA have a higher incidence of and mortality from prostate cancer (PCa), with a longstanding debate about the cause for these worse outcomes. This review examines differences in tumour biology and socioeconomics for African–American and Non-Hispanic White (NHW) men to answer the question ‘why AA men face higher risks for lethal PCa’ and draw a management consensus to redress the imbalance.Recent findingsRecent evidence from over the past 2 years suggests the reasons why African–American men face a higher risk of lethal PCa are multifactorial, with contributions from differences in tumour biology as well as socioeconomic and healthcare access factors. Regarding tumour biology, genomic and transcriptome profiling suggests African–American men have upregulated expression of genes related to inflammatory pathways with downregulation of DNA repair genes. In contrast, NHW men have higher DNA repair pathways and metabolic pathways involving glycolysis and cell cycle activity. In addition, epidemiological evidence suggests equal healthcare access ensures equal PCa specific outcomes, implying African–American men's disease is not inherently more lethal. However, differences in tumour biology remain, which may explain specific differences in PCa incidence and the clinical findings of African–American men's increased response to immunotherapy and radiotherapy in recent trials.SummaryRegardless of racial differences in disease outcomes and the factors causing them, African–American and NHW men seem to have diseases unique to their ancestry. This supports the exploration of personalized PCa treatment approaches, leveraging translational basic science research to uncover these differences and devise specific individualized methods therapeutic regimes to address them.

Differences in Prostate Cancer Incidence and Mortality in Lower Saxony (Germany) and Groningen Province (Netherlands): Potential Impact of Prostate-Specific Antigen Testing.

BackgroundProstate cancer (PCa) is the most frequent cancer among men in Europe. Differences in PCa incidence around the world can be partly explained by variations in recommendations for prostate-specific antigen (PSA), particularly for early detection. For example, the PSA testing policy is more conservative in the Netherlands than in Germany. To better understand the relationship between PSA testing recommendations and PCa incidence, stage distribution, and mortality, we compared these variables over time between Lower Saxony in northwestern Germany and the neighboring province of Groningen in the Netherlands.MethodsPopulation data, tumor stage- and age group-specific PCa incidence (ICD-10 C61) and mortality rates for Lower Saxony and Groningen were obtained from the Lower Saxony Epidemiological Cancer Registry, the Netherlands Comprehensive Cancer Organization, and Statistics Netherlands for 2003–2012. Incidence and mortality rates per 100,000 person-years were age-standardized (ASR, old European standard). Trends in age-standardized incidence rates (ASIR) and mortality rates (ASMR) for specific age groups were assessed using joinpoint regression.ResultsThe mean annual PCa ASIR between 2003 and 2012 was on average 19.9% higher in Lower Saxony than in Groningen (120.5 vs. 100.5 per 100,000), while the mean annual ASMR was on average 24.3% lower in Lower Saxony than in Groningen (21.5 vs. 28.4 per 100,000). Between 2003 and 2012, the average annual percentage change (AAPC) in PCa incidence rates did not change significantly in either Lower Saxony (−1.8%, 95% CI −3.5, 0.0) or Groningen (0.2%, 95% CI −5.0, 5.7). In contrast, the AAPC in mortality rate decreased significantly during the same time period in Lower Saxony (−2.5%, 95% CI −3.0, −2.0) but not in Groningen (0.1%, 95% CI −2.4, 2.6).ConclusionsHigher PCa incidence and lower PCa-related mortality was detected in Lower Saxony than in Groningen. Although recommendations on PSA testing may play a role, the assessed data could not offer obvious explanations to the observed differences. Therefore, further investigations including data on the actual use of PSA testing, other influences (e.g., dietary and ethnic factors), and better data quality are needed to explain differences between the regions.

Racial disparity in prostate cancer in the African American population with actionable ideas and novel immunotherapies.

BackgroundAfrican Americans (AAs) in the United States are known to have a higher incidence and mortality for Prostate Cancer (PCa). The drivers of this epidemiological disparity are multifactorial, including socioeconomic factors leading to lifestyle and dietary issues, healthcare access problems, and potentially tumor biology.Recent findingsAlthough recent evidence suggests once access is equal, AA men have equal outcomes to Caucasian American (CA) men, differences in PCa incidence remain, and there is much to do to reverse disparities in mortality across the USA. A deeper understanding of these issues, both at the clinical and molecular level, can facilitate improved outcomes in the AA population. This review first discusses PCa oncogenesis in the context of its diverse hallmarks before benchmarking key molecular and genomic differences for PCa in AA men that have emerged in the recent literature. Studies have emphasized the importance of tumor microenvironment that contributes to both the unequal cancer burden and differences in clinical outcome between the races. Management of comorbidities like obesity, hypertension, and diabetes will provide an essential means of reducing prostate cancer incidence in AA men. Although requiring further AA specific research, several new treatment strategies such as immune checkpoint inhibitors used in combination PARP inhibitors and other emerging vaccines, including Sipuleucel‐T, have demonstrated some proven efficacy.ConclusionGenomic profiling to integrate clinical and genomic data for diagnosis, prognosis, and treatment will allow physicians to plan a “Precision Medicine” approach to AA men. There is a pressing need for further research for risk stratification, which may allow early identification of AA men with higher risk disease based on their unique clinical, genomic, and immunological profiles, which can then be mapped to appropriate clinical trials. Treatment options are outlined, with a concise description of recent work in AA specific populations, detailing several targeted therapies, including immunotherapy. Also, a summary of current clinical trials involving AA men is presented, and it is important that policies are adopted to ensure that AA men are actively recruited. Although it is encouraging that many of these explore the lifestyle and educational initiatives and therapeutic interventions, there is much still work to be done to reduce incidence and mortality in AA men and equalize current racial disparities.

Implementing Community-Based Prostate Cancer Education in Rural South Carolina: a Collaborative Approach Through a Statewide Cancer Alliance.

The purpose of this study was to evaluate the impact of implementing community-based prostate health education programs in rural communities. Prostate cancer (PrCA) remains one of the most common cancers among men, and a growing body of literature demonstrates that large interracial differences in PrCA incidence and mortality rates consistently disfavor African Americans in comparison to European Americans. It also is evident, despite the overall decrease in cancer death rates in the USA in recent decades, rural areas are experiencing a reduction in death rates much more slowly. In this study, education session content focused on PrCA risk factors, symptoms, screening, healthy diet and exercise, treatment options, and provider communication strategies. Forty individuals participated and completed pre/post-education program surveys to assess changes in PrCA knowledge and cancer decision-making. Participants showed improvements in education and awareness following the session, and overall impressions of the program were consistently positive as exhibited by participants' answers on a satisfaction survey. The findings demonstrate the real need both in terms of research to understand the underlying problem and to provide practical solutions that can be implemented to reverse the current situation. The results obtained support community-based education programs as an effective means of delivering PrCA prevention, screening, and treatment information to rural communities.

Abstract D115: The interplay between rurality-urbanicity and race in prostate cancer risk, treatment, and survival in the United States

Abstract Background. In this study, we compared prostate cancer incidence and survival between rural and urban settings in the US, using a recently released census-tract rurality-urbanicity metric that serves as a proxy for geographical access to care. We also examined the associations between rurality and receipt of definitive treatment and further examined whether rural-urban status serves as an explanatory factor for observed race differences in prostate cancer incidence, treatment, and survival. Methods. Using data from the Surveillance, Epidemiology, and End Results program we identified prostate cancer patients newly diagnosed between 2000 and 2015, aged 45 years and older. Patients were classified as residing in a ‘rural’ or ‘urban’ setting based on the US Department of Agriculture’s 2-level Rural Urban Commuting Area (RUCA) measure. We defined ‘definitive treatment’ as receipt of radical prostatectomy (RP) among patients diagnosed with locoregional disease. To compare rural and urban settings we estimated relative measures for prostate cancer incidence, odds of treatment receipt, and prostate cancer survival using Poisson, logistic, and Cox regression models, respectively. We adjusted regression models for age, race, stage, or treatment, where applicable. Results. Between 2000 and 2015, men in the rural US were slightly less likely to be diagnosed with prostate cancer when compared with urban US men (incidence rate ratio (IRR) = 0.89; 95% CI: 0.88, 0.90), but were at higher risk of prostate cancer death (hazard ratio (HR) = 1.16; 95% CI: 1.13, 1.19). Patients diagnosed with locoregional disease in rural settings were also less likely to receive RP compared with their urban counterparts (odds ratio (OR) = 0.91; 95% CI: 0.89, 0.92) and were more likely to receive non-radical surgical interventions (OR = 1.31; 95% CI: 1.28, 1.35). In general, race differences were not evident by rural-urban status. Black men, however, were more likely to receive a prostate cancer diagnosis irrespective of geographical setting when compared with white men (rural IRR = 1.50; 95% CI: 1.46, 1.54 and urban IRR = 1.69; 95% CI: 1.64, 1.73). Black men were also substantially less likely to receive RP (OR = 0.49; 95% CI: 0.48, 0.49). With respect to survival, Asian or Pacific Islander men were at lower risk of prostate cancer death compared with white men (HR = 0.78; 95% CI: 0.75, 0.81). By contrast, American Indian/Alaskan Native and black men had the highest risks of death (HR = 1.26; 95% CI: 1.11, 1.43 and HR = 1.25; 95% CI: 1.22, 1.28, respectively). Conclusions. Observed differences in prostate cancer incidence, treatment, and survival may reflect spatial differences in access to cancer prevention and cancer care. Rural-urban status does not appear to modify racial/ethnic differences in prostate cancer incidence and survival. Citation Format: Eboneé N Butler, Michael B Cook. The interplay between rurality-urbanicity and race in prostate cancer risk, treatment, and survival in the United States [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 D115.

Abstract C016: Racial differences in the incidence of fatal prostate cancer in two countries: An ecological comparison of the United States and England

Abstract Background: Differential uptake of prostate-specific antigen (PSA) testing in the US and UK has been linked to between-country differences in prostate cancer incidence. In the US, men of African ancestry have been shown to have a higher incidence of prostate cancer that is ultimately fatal compared with men of European ancestry, thus prompting calls for precision prevention approaches to screening. To assess whether temporal and racial differences are evident in the UK, we assessed the incidence of fatal prostate cancer in the US and England during a period of evolving screening recommendations and practices in both countries. Methods: Using data from the Surveillance, Epidemiology, and End Results program and Public Health England's National Cancer Registration and Analysis Service, we identified prostate cancer patients newly diagnosed between 1995 and 2005, aged 45-84 years old. We defined fatal prostate cancer as death attributed to the disease within 10 years of diagnosis. To evaluate incidence trends across the 11-year study period, we used age-period-cohort modeling to calculate estimated annual percentage change (EAPC) and joinpoint regression analysis to identify periods of significant change. Results: In the US, 9% (n=38,409) of the 429,541 prostate cancer cases were fatal, compared with 17% (n=39,249) of the 228,615 cases in England. The age-adjusted incidence of fatal prostate cancer declined in the US by -4.2% per year (95%CI: -4.6%, -3.8%) and increased in England by 7.7% per year (95%CI:7.2%, 8.3%). From 2002-2005, the US experienced a more rapid decline in the incidence of fatal disease (EAPC = -6.4%; 95%CI: -8.3%, -4.5%) while rates in England continued to increase, albeit to a lesser degree (EAPC = 4.3%; 95%CI: -0.1%, 8.9%). Temporal trends for each country did not differ by race. However, a black-to-white difference persisted across the study period, with black men in both the US and England experiencing 2-to-3-fold higher incidence rates of fatal prostate cancer compared with white men. Conclusions: During a period of increased PSA testing in the US and relatively low, but growing, use in England, we observed opposing trends for the incidence of fatal prostate cancer between the two countries. Our ecological study suggests that country-specific screening practices may influence temporal trends for the incidence of fatal prostate cancer similarly for black and white men, though a disparity persists in the absolute rate of disease occurrence between the two groups. Citation Format: Eboneé N. Butler, Scott P. Kelly, Victoria H. Coupland, Philip R. Rosenberg, Michael B. Cook. Racial differences in the incidence of fatal prostate cancer in two countries: An ecological comparison of the United States and England [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr C016.

Educational level and first-time PSA testing in general practice

Introduction: Different patterns in the use of prostate-specific antigen (PSA) testing might explain socioeconomic differences in prostate cancer incidence and mortality. We examined the association between socioeconomic position, measured as education and first-time PSA testing in general practice.Material and Methods: A population-based cohort study of men aged 45–79 years without prior prostate cancer diagnosis living in the Capital Region of Denmark between 2000 and 2014. Information on socioeconomic indicators (education, income, cohabitation status and work market affiliation), prostate cancer diagnoses, and vital status were obtained from national registries. Date of first PSA test was obtained from the Copenhagen Primary Care Laboratory database. Temporal trends of PSA testing were calculated as annual age-standardised incidence rates and the association was examined by a multivariable Cox proportional hazards model.Results: The cohort consists of 431,997 men of which 105,476 (24%) had a first-time PSA test in the study period. Men with longer education, higher income, living with a partner, and employed had higher rates of PSA testing. For men with short education, the rate of PSA test was 28.3 tests per 1000 person-years compared to 31.2 tests among men with long education. The fully adjusted hazard ratio for a first PSA test among men with short education was 0.87 (95% CI, 0.85–0.89) compared to men with long education.Conclusion: The association between education and first-time PSA testing indicates socioeconomic disparities in health care utilisation, which could explain part of the observed socioeconomic difference in prostate cancer incidence and mortality.

The incidence, mortality, and risk factors of prostate cancer in Asian men.

The objective of this review was to describe the epidemiology and risk factors of prostate cancer (PCa) in Asian populations. English language publications published over the last 10 years covering studies on the incidence, mortality, and risk factors of PCa in Asia were reviewed. The incidence of PCa in Asia is rising but is still significantly lower than that in Western countries. Studies in Asia indicated that the consumption of red meat, fat, dairy, and eggs was associated with a higher risk for PCa. Age and family history were also found to be risk factors. The emergence of genetic data indicates that different genetic backgrounds between Asian and Western populations play a role in the observed differences in PCa incidence. The lower incidence of PCa in Asian men than in Western men may in part be due to a lack of systematic prostate-specific antigen screening, but environmental and genetic factors also play a role.

Difference in prostate cancer incidence around sixty years: effects of age and metabolic diseases.

We examined the risk of prostate cancer in the Korean population stratified on the basis of age group and risk based on metabolic diseases, using National Health Insurance System (NHIS) data. Of the 51,827,813 people from the NHIS data in 2015, 10,879,591 men without prostate cancer who underwent a health examination were analyzed. The risk of prostate cancer was analyzed with stratification by age. Multivariate‐adjusted Cox regression analysis was conducted to examine the association between prostate cancer and metabolic diseases by age groups. The risk of prostate cancer increased continuously with age and 59 years may be a point of inflection. The hazard ratio (HR) of prostate cancer development rose sharply as that age point passed. The population with metabolic diseases was more likely to develop prostate cancer than the population without any of these components. In addition, the incidence rate ratio (IRR) decreased from the youngest age group to the age group comprising 55–59 year olds. Beyond this age group, there was a plateau. The relative risk for prostate cancer associated with metabolic diseases also showed divergent associations with age. The risk of prostate cancer increased continuously with age and the peak Youden index was at 59 years. The relative risk for prostate cancer according to metabolic diseases also showed divergent associations beyond 59 years of age. Therefore, setting the age threshold at 59 years would improve the present clinical risk stratification for prostate cancer in Korea.

Trends in prostate cancer incidence between 1996 and 2013 in two Swiss regions by age, grade, and T-stage.

To investigate differences in prostate cancer incidence between two distinct Swiss regions from 1996 to 2013 stratified by age group, grade, and T-stage. The dataset included 17,495 men living in Zurich and 3,505 men living in Ticino, diagnosed with prostate cancer between 1996 and 2013. We computed age-standardized incidence rates per 100,000 person-years using the European Standard Population. Trends were assessed using JoinPoint regression analysis Software. Age-standardized incidence rates were generally higher in Zurich compared to Ticino but the difference decreased over time. Incidence rates increased significantly up to 2002 in Zurich and 2007 in Ticino and then decreased. A statistically significant increase was observed for men aged < 65 years, for grade 3 tumors, and for T-stage 2 and 3 tumors. The largest decrease was seen for grade 1 tumors. Furthermore, the incidence of tumors of unknown grade or T-stage decreased significantly in both regions. The trends in prostate cancer incidence rates were similar in both regions, although on a higher level in Zurich compared to Ticino. However, the difference decreased over time. The distribution of T-stage and grade did not explain the difference in incidence rates. Different use of opportunistic screening may play a role.

Abstract 1303: A genome-wide association study of prostate cancer in Latinos

Abstract Recent studies estimate that individuals of African or Latin American ancestry represent less than 4% of samples analyzed to date in genome-wide association studies. The clinical value of genetic information in guiding personalized medicine in populations of non-European ancestry will require additional discovery and risk locus characterization efforts in these populations. Here, we performed a genome-wide association study (GWAS) meta-analysis of prostate cancer in Latino men to search for risk loci that may be important in this population. We combined GWAS data for 1034 cases and 1046 controls genotyped with the Illumina 660 Beadarray with GWAS data for 1235 cases and 1053 controls genotyped with the Illumina Oncoarray as part of the ELLIPSE U19 GAME-ON Consortium. A total of ~11 million genotyped and imputed SNPs of ≥1% frequency were tested for association with prostate cancer risk in logistic regression models controlling for age, study and genetic ancestry. Genome-wide significant associations were observed with 24 variants all located at 8q24 (128.484-128.548), and which capture the first reported prostate cancer susceptibility locus in ‘region 1’ of 8q24. The most significant association genome-wide was with SNP rs7824776 (risk allele frequency, 0.35; OR=1.69, p=3.4x10-11). No novel genome-wide significant associations were noted outside of 8q24. We observed a high degree of generalizability of known prostate cancer risk loci, with 78 (76%) of the 103 known risk variants having effects that were directionally consistent in their association with prostate cancer risk as previously reported, of which 31 (30%) were statistically significant with p &amp;lt; 0.05. In addition to these findings from the largest GWAS of prostate cancer in Latinos conducted to date, we will also present the results investigating effect heterogeneity by local ancestry (i.e. proportion Native American vs. European). In addition, we will present a comparison of polygenic risk models between Latinos, African Africans and men of European ancestry that incorporate the known risk loci to better understand how genetic risk tracks with population differences in prostate cancer incidence. Citation Format: Hannah Hopp, Sue Ingles, Chad Huff, Xin Sheng, Brandi Weaver, Mariana Stern, Sara Strom, Ian Thompson, David Conti, Christopher A. Haiman. A genome-wide association study of prostate cancer in Latinos [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 1303. doi:10.1158/1538-7445.AM2017-1303

Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes.

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR.

Abstract B18: Interactions between finasteride and vitamin D-related polymorphisms is associated with prostate cancer risk in African American men

Abstract Background: The difference in prostate cancer incidence and survival between European American (EuAm) and African American (AfAm) men is an important health disparity. Vitamin D (VitD) has been linked to key carcinogenesis-related processes and there is strong evidence of cross talk between the androgen and VitD signaling pathways. AfAm men are more likely to be VitD deficient compared to EuAm men which could be one reason for the health disparity. The current study examined genetic variability in the VitD pathway in relation to prostate cancer risk and investigated whether finasteride, a 5α-reductase inhibitor that blocks the metabolism of testosterone, influenced the relationship of cancer risk in EA and AfAm men with VitD-related polymorphisms. Materials and Methods: This nested case-control study included 2,356 men (EuAm: 1,091 cases and 1,088 controls; AfAm: 47 cases, 130 controls) from the Prostate Cancer Prevention Trial, a randomized double-blind, placebo-controlled trial of finasteride for the primary prevention of prostate cancer. In EuAm men, controls were frequency matched to cases on distributions of age, first degree family history of prostate cancer and treatment arm. Due to smaller numbers, all available AfAm men were selected. Participants underwent for-cause or end of study prostate biopies with central pathology review to determine case or control status. Twenty-nine SNPs from 14 genes identified from previous studies as being associated with VitD levels and/or prostate cancer were genotyped from buffy coats using the Illumina VeraCode GoldenGate assay (Illumina Inc; San Diego, CA). Odds ratios were calculated to determine associations of SNP genotypes with prostate cancer risk. Interaction was ermined by adding an interaction term to the logistic models. All statistical tests are 2-sided with p&amp;lt;0.05 considered statistically significant. SAS (ver 9.2, Cary NC) and R (2.15.1, Vienna Austria) were used for all analyses. Results: Three SNPs (C1orf88 rs6599638, CYP24A1 rs6013897, HSD3B1 rs1856888) showed significant interaction by treatment group (finasteride vs. placebo) in AfAm men only (p-interaction for rs6599638, rs6013897, rs1856888 was 0.01, 0.02 and 0.02, respectively). None of the SNPs were associated with cancer in EuAm men and there was no evidence of interaction by treatment group in EuAm men. SNPs rs6599638 and rs6013897 were not associated with cancer in AfAm men in the placebo group. In AfAm men taking finasteride, however, the odds ratios (OR) were significant [rs6599638 AA genotype (7 cases/ 5 controls) compared to AG/GG (12 cases/77 controls) OR= 10.84, 95%CI: 2.77, 45.5; p=0.001; for rs6013897 AA/AT genotypes (13 cases/31 controls) compared to TT (7 cases/51 controls) OR= 3.08, 95%CI: 1.10, 8.60; p=0. 03]. For the rs1856888 SNP, the GG/AG genotypes were protective in the AfAm placebo group [GG/AG (11 cases/33 controls) compared to AA (16 cases/17 controls) OR=0.31, 95%CI: 0.11, 0.84, p= 0.02] but the OR increased to 1.98 in the AfAm finasteride group (p=0.23). The potential impact is limited for rs6599638 as only 10% of AfAm controls have the AA genotype. The impact is larger for rs6013897 and rs1856888 with 41% and 62% of controls with the AA/AT and GG/AG genotypes, respectively. Numbers were too small to examine associations by Gleason grade. Conclusions: There appears to be differential response to finasteride by race and genotype in three of the 29 VitD pathway SNPs examined in the current study. In these three SNPs in the presence of finasteride, the risk genotypes were associated with an increased odds for cancer in AfAm men and not EuAm men. This implies that finasteride may need to be prescribed with caution to some AfAm men. These results should be confirmed in a larger sample size. Citation Format: Kathleen C. Torkko, Cathee Till, Phyllis J. Goodman, Catherine M. Tangen, Adrie van Bokhoven, M. Scott Lucia, Ian M. Thompson, Jr., Ulrike Peters, Marian L. Neuhouser. Interactions between finasteride and vitamin D-related polymorphisms is associated with prostate cancer risk in African American men. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B18.

Ultraviolet index and racial differences in prostate cancer incidence and mortality

Studies suggest that low levels of vitamin D may be associated with prostate cancer, and darker skin reduces the body's ability to generate vitamin D from sunshine. The impact of sunshine on racial disparities in prostate cancer incidence and mortality is unknown. Using the Surveillance, Epidemiology, and End Results program database, the authors calculated age-adjusted prostate cancer incidence rates among black and white men aged ≥ 45 years by race and county between 2000 and 2009 (N = 906,381 men). Similarly, county-level prostate cancer mortality rates were calculated from the National Vital Statistics System (N = 288,874). These data were linked with the average monthly solar ultraviolet (UV) radiation index by county and data regarding health, wellness, and demographics. Multivariable regression analysis was used to assess whether increases in the UV index (in deciles) moderated the association between black race and the incidence and mortality of prostate cancer. Compared with counties in the lowest UV index decile, prostate cancer incidence rates for white and black men were lower in counties with a higher UV index (all Ps ≤ 0.051). Incidence rates were higher for black men versus white men, but the difference by race was less for counties in the fourth to fifth UV index deciles versus those in the first decile (Ps ≤ 0.02). Mortality rates also were found to decrease with increasing UV index for white men (Ps ≤ 0.003), but increase for black men, and an unexplained increase in racial differences in mortality rates was observed with an increasing UV index. Racial disparities in the incidence of prostate cancer were larger in some areas with less sunshine. Additional research should confirm the findings of the current study and assess whether optimizing vitamin D levels among black men can reduce disparities.

Targeting psychoemotional stress to treat prostate cancer

Targeting psychoemotional stress to treat prostate cancer

Prostate cancer incidence and mortality in rural men - a systematic review of the literature

Prostate cancer is a common health problem in men worldwide. This systematic review has been undertaken to determine if there are differences in incidence of and mortality from prostate cancer between rural and urban men. The understanding of geographical patterns of prostate cancer incidence and mortality is necessary in order to identify and assess any disparities between rural and urban residents in gaining access to healthcare services, such as screening, diagnosis and treatment. Medline, CINAHL and Embase were searched using relevant mesh phrases, such as 'prostate cancer incidence rural' or 'prostatic neoplasms mortality rural'. Secondary literature and reports not published in peer-reviewed journals were included if inclusion criteria had been met. The following inclusion criteria were applied: cohort (population-based study) of adult men, diagnosis of prostate cancer, comparing rural and urban groups, and incidence or mortality with available statistical parameters as outcome. In total, 25 studies were found to fit the inclusion criteria. Sixteen cohort studies were identified that examined incidence of prostate cancer in rural and urban populations, while 18 studies focused on mortality. Nine of these publications discussed both aspects. Twenty of these studies were published in scientific journals, while five were reports identified through secondary literature search. Prostate cancer incidence was found to be higher in urban men, while mortality patterns seemed to vary to some degree depending on different definitions of rural/urban groups, as well as on variations in demographic factors and study periods. There is evidence, however, that after prostate-specific antigen testing was introduced death rates tended to be higher in rural men with prostate cancer. The review of the literature showed that in spite of inconsistent definitions of rural/urban categories among studies the majority reported higher incidence rates in urban men. This finding suggests that rural men are less likely to be screened and less likely to be subsequently diagnosed with prostate cancer. Although mortality patterns tended to be heterogeneous, there was some evidence that rural residents with prostate cancer experience higher death rates. It would be beneficial if future studies take into consideration factors such as stage at initial diagnosis, ethnicity, and socioeconomic and health status when assessing differences in cancer outcomes. Few studies in this review accounted for one or more of these variables, although there are indications that they contribute to differences in prostate cancer incidence and mortality between rural and urban populations.