Affect Prostate Cancer Risk Research Articles

Association of neighborhood gentrification with prostate cancer and immune markers in African American and European American men.

Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer and serum proteome-defined inflammation and immune function in a diverse cohort. The case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA and 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression, and MANOVA, were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. Adjusting for individual socioeconomic status (SES), continuous NGI was positively associated with prostate cancer among all men (odds ratio [OR] 1.07, 95% confidence interval [CI] 1.01-1.14). AA and low-income men experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification, whereas EA men experienced reduced odds of regional/metastatic cancer with increased gentrification in SES-adjusted analyses. Continuous NGI also associated with mortality among men presenting with localized disease and low-income men in SES-adjusted Cox regression analyses. NGI was not associated with serum proteome-defined chemotaxis, inflammation, and tumor immunity suppression. Findings show that neighborhood gentrification associates with prostate cancer and mortality in this diverse population albeit associations were heterogenous within subgroups. The observations suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms.

Abstract B088: Association of neighborhood gentrification with prostate cancer in African American and European American men

Abstract Abstract Background: Prior studies showed that neighborhood deprivation increases the risk of lethal prostate cancer. However, the role of neighborhood gentrification in prostate cancer development and outcome remains poorly understood. We examined the relationships of gentrification with prostate cancer in a diverse cohort. Methods: This case-control study included 769 cases [405 African American (AA), 364 European American (EA) men] and 1023 controls (479 AA, 544 EA), with 219 all-cause and 59 prostate cancer-specific deaths among cases. Geocodes were linked to a neighborhood gentrification index (NGI) derived from US Census data. Cox and logistic regression were used to determine associations between NGI, as continuous or quintiles (Q), and outcomes. Results: Adjusting for individual socioeconomic status (SES), continuous NGI was associated with prostate cancer among all men (odds ratio (OR) 1.07, 95%CI 1.01-1.14). AA experienced the highest odds of prostate cancer when residing in tracts with moderate gentrification (Q3 OR 1.79, 95%CI 1.11-2.88). However, EA men experienced a reduced risk of regional/metastatic cancer (risk ratio 0.62, 95%CI 0.40-0.97) with increased gentrification, adjusting for SES. Continuous NGI was associated with mortality among men presenting with localized disease (all-cause HR 1.10, 95%CI 1.01-1.20; disease-specific SHR 1.16, 95%CI: 1.01-1.33). Conclusions: Findings show that neighborhood gentrification modestly associates with prostate cancer and mortality in this diverse population. They suggest that changing neighborhood socioeconomic environments may affect prostate cancer risk and outcome, likely through multifactorial mechanisms. Citation Format: Catherine M. Pichardo, Adaora Ezeani, Margaret Pichardo, Tanya Agurs-Collins, Tiffany M. Powell-Wiley, Brid Ryan, Tsion Minas, Maeve Bailey-Whyte, Wei Tang, Tiffany H. Dorsey, William Wooten, Christopher A. Loffredo. Association of neighborhood gentrification with prostate cancer in African American 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 B088.

Do Obesity-Related Traits Affect Prostate Cancer Risk through Serum Testosterone? A Mendelian Randomization Study.

This study aimed to investigate whether testosterone mediates or confounds the effect of obesity-related traits on prostate cancer (PCa) using Mendelian randomization (MR) analysis. Data of obesity-related traits (body mass index [BMI], waist-to-hip ratio [WHR], and waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) were obtained from up to 806,834 people of European ancestry; data of testosterone (bioavailable testosterone [BT], total testosterone [TT], and sex hormone-binding globulin [SHBG]) were extracted from up to 194,453 participants in the UK Biobank; and the summary-level data of PCa (79,194 cases and 61,112 controls) were obtained from the PRACTICAL consortium. The results supported the causal relationship between higher BMI and a reduced risk of PCa (OR = 0.91, 95% confidence interval [CI]: 0.86-0.96). Furthermore, increased BT levels were associated with an elevated risk of PCa (OR = 1.15, 95% CI: 1.06-1.24). Importantly, our analysis revealed a unidirectional causal effect-higher BMI was linked to lower BT levels (beta = -0.27, 95% CI: -0.3--0.24), but not the other way around. This suggests that BT may mediate the effect of BMI on PCa rather than confound it. Our multivariable MR results further demonstrated that considering BT as a mediator led to the weakening of BMI's effect on PCa risk (OR = 0.97, 95% CI: 0.90-1.05), while the impact of BT on PCa remained unchanged when accounting for BMI. Moreover, we identified a significant indirect effect of BMI on PCa risk (OR = 0.96, 95% CI: 0.94-0.98). Our study provided genetic evidence that serum BT can mediate the effect of BMI on the risk of PCa, indicating the possible mechanism by which obesity reduces PCa risk.

MP77-05 PROSTATE CANCER TRENDS AMONG INDIVIDUAL ASIAN AND PACIFIC ISLANDERS (AAPI) POPULATIONS IN HAWAII

You have accessJournal of UrologyCME1 Apr 2023MP77-05 PROSTATE CANCER TRENDS AMONG INDIVIDUAL ASIAN AND PACIFIC ISLANDERS (AAPI) POPULATIONS IN HAWAII Lauren Muramoto, Brenda Hernandez, and Tom Feng Lauren MuramotoLauren Muramoto More articles by this author , Brenda HernandezBrenda Hernandez More articles by this author , and Tom FengTom Feng More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003351.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Asians and Pacific Islanders (AAPIs) are often grouped together as a single racial demographic when reporting prostate cancer trends despite the heterogeneity within this community. Hawaii’s multi-ethnic community poses a unique environment to study the epidemiology of prostate cancer. We examine differences in incidence and mortality of prostate cancer among AAPIs within Hawaii. METHODS: Data were obtained from the Hawaii Tumor Registry Cancer at a Glance 2014-2018 report. All reported rates were age adjusted per 100,000 to the 2000 US standard population. Differences in incidence and mortality rates were compared among the major AAPI groups: Chinese, Filipino, Japanese, and Native Hawaiian. RESULTS: Prostate cancer is the most common cancer diagnosed in men in Hawaii with an incidence of 22.8% and responsible for 9.6% of cancer related deaths from 2014-2018. Incidence rates among the four major AAPI groups were not statistically different (Figure 1a). Despite this, mortality rates were significantly lower in Chinese (5.5 per 100,000) and Japanese (8.7) compared to Filipinos (16.4) and native Hawaiians (21.6, p<0.05, Figure 1b). Native Hawaiians had the lowest incidence rate (80.2) but had the highest mortality rates among Asians (21.6 per 100,000). Filipinos, despite having similar incidence as Chinese and Japanese, had much higher mortality rates (p<0.05) and the highest proportion of advanced prostate cancer 34.7% at diagnosis. CONCLUSIONS: Hawaii’s diversity plays an important role in reporting cancer incidence and mortality among AAPI. Differences could be related to access to care, genetics, education level or lifestyle related exposures. These data support the need to disaggregate AAPI subpopulations to better understand individual prostate cancer risk profiles. Further research is needed to determine these differing factors among AAPI ethnicities affect prostate cancer risk and outcomes. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1103 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Lauren Muramoto More articles by this author Brenda Hernandez More articles by this author Tom Feng More articles by this author Expand All Advertisement PDF downloadLoading ...

Healthy lifestyle, Agent Orange exposure, and inherited PCa risk: An analysis of the Million Veteran Program.

210 Background: Prostate cancer (PCa) risk is understood to be mostly unmodifiable and inherited, but there is evidence that environmental and behavioral factors may also contribute. A recent study of health professional cohorts suggests a healthy lifestyle can mitigate a high inherited risk of lethal PCa. It is unknown how modifiable factors affect PCa risk in more diverse populations. Our objective was to determine the effects of healthy lifestyle and Agent Orange exposure on PCa risk when accounting for race/ethnicity, family history, and genetic risk in a diverse population. Methods: The Million Veteran Program (MVP) is a national, population-based cohort study of United States military veterans conducted 2011-2021 with 590,750 male participants available for analysis. Healthy lifestyle was quantified as: A healthy lifestyle score (range 0-3) was calculated with a point assigned for each of the following at MVP enrollment: not a current smoker, body mass index (BMI) 30 and strenuous activity 2 days per week. Agent Orange exposure was obtained from VA records. Genetic risk was assessed via a polygenic hazard score using genotype data. Results: Healthy lifestyle was independently associated with reduced metastatic PCa (HR 0.82, 95% CI 0.77–0.87, p&lt;0.001) and fatal PCa (HR 0.76, 95% CI 0.68–0.86, p&lt;0.01) when accounting for family history, genetic risk, and race/ethnicity. The benefit of healthy lifestyle was also observed in Black participants on subset analysis. Agent Orange exposure was an independent factor for PCa diagnosis (HR 1.06, 95% CI 1.04-1.09). Conclusions: Adherence to a healthy lifestyle is associated with reduced risk of metastatic or fatal PCa, which offsets inherited risk.

Does obesity-related traits affect prostate cancer risk through serum testosterone? A Mendelian randomization study

Does obesity-related traits affect prostate cancer risk through serum testosterone? A Mendelian randomization study

The CYP19A1 (TTTA)n Repeat Polymorphism May Affect the Prostate Cancer Risk: Evidence from a Meta-Analysis.

Abnormal aromatase (CYP19A1) expression may participate in prostate cancer (PCa) carcinogenesis. However, the results of studies on the CYP19A1 gene polymorphisms and PCa are conflicting. This meta-analysis aimed to systematically evaluate the associations between the CYP19A1 Arg264Cys polymorphism and the (TTTA)n repeat polymorphism and PCa. Electronic databases (PubMed, EmBase, ScienceDirect, and Cochrane Library) were comprehensively searched to identify eligible studies. The strength of the association between the Arg264Cys polymorphism and PCa was assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) in allelic, dominant, recessive, homozygous, and heterozygous genetic models. To analyze the impact of the (TTTA)n repeat polymorphism, we sequentially took the N-repeat allele (where N equals 7,8,10,11,12, and 13) as the minor allele and the sum of all the other alleles as the major allele. The ORs and 95% CIs were calculated in the allelic model; this analysis was performed individually for each repeat number. Pooled estimates of nine studies addressing the Arg264Cys polymorphism indicated that this polymorphism was not associated with PCa risk in the overall population or in the Caucasian or Asian subgroups. The 8-repeat allele in the (TTTA)n repeat polymorphism increased PCa risk in the overall population (OR = 1.34, 95% CI = 1.14–1.58, p = .001) and in the subgroup with population-based (PB) controls (OR = 1.41, 95% CI = 1.13–1.74, p = .002) as well as in the subgroup using capillary electrophoresis to identify this polymorphism (OR = 1.34, 95% CI = 1.09–1.65, p = .006).The meta-analysis indicated that the CYP19A1 (TTTA)n repeat polymorphism, but not the Arg264Cys polymorphism, may affect PCa risk.

Research advances in the relationship of dietary factors and prostate cancer risk

Prostate cancer is the second most common malignancy in men worldwide. An increasing trend for prostate cancer incidence was observed in China. Enormous studies have been conducted to investigate the association between dietary factors and prostate cancer, however conflicted results were obtained. Red meat, processed meat, and dairy products consumption were reported to be associated with the increased prostate cancer risk, while tomatoes, soybeans and green tea might reduce the risk of prostate cancer occurance. However, no consensus could be reached without strong evidence. Furthermore, further studies are needed to investigate the association between vitamin and mineral supplements and prostate cancer risk. Some studies reported that men with higher dietary inflammatory index scores increased prostate cancer risk. There may be a long susceptible period when dietary factors affect prostate cancer risk, which poses challenges for collecting exposure and the follow-up. Measure bias and detection bias are the main reasons which impair the authenticity of studies on the relationship of dietary factors and prostate cancer risk. Researchers should apply various methods to measure participants' dietary consumption levels and ascertain essential outcomes, such as prostate cancer death. This article reviews updated epidemiological evidences on the association of dietary factors and prostate cancer, aims to benefit future nutritional epidemiology studies focus on the prostate cancer prevention.

AUTHOR REPLY

We wish to expand on some of the excellent points made by Dr. Nyame in his editorial on our paper. While we also view race itself as largely a social construct, we recognize that important biological and environmental risk factors cluster by race and thereby affect prostate cancer risk and mortality. Such factors include vitamin D deficiency, genetic background and tumor gene expression along with factors which are intertwined with socioeconomic deprivation, including access to care, screening and smoking behaviors, body composition and diet. 1 Smith ZL Eggener SE Murphy AB African-American prostate cancer disparities. Curr Urol Rep. 2017; 18: 81 Crossref PubMed Scopus (31) Google Scholar Translational research on biomarkers tends to move ahead rapidly, and early studies often do not include enough Black men to permit analyses to detect differences in predictive value that could lead to race-specific test thresholds or alternate testing strategies. Thus, initial estimates of the balance between risk and harm related to a biomarker could be inapplicable for Black men, and opportunities to reduce the racial disparity could be lost.

Patient- and area-level predictors of prostate cancer among South Carolina veterans: a spatial analysis.

Racial and socio-economic status (SES) disparities exist in prostate cancer (PrCA) incidence and mortality. Less is known regarding how geographical factors, including neighborhood social vulnerability and distance traveled to receive care, affect PrCA risk. The purpose of this research was to use the Veterans Administration Medical System, which provides a unique means for studying PrCA epidemiology among diverse individuals with ostensibly equal access to healthcare, to determine whether area-level characteristics influence PrCA incidence while accounting for individual-level risk factors. From the US Veteran's Health Administration (VHA) electronic medical records (EMR) database from January 1999 to December 2015, we identified 3,736 PrCA patients and 104,017 cancer-free controls from South Carolina (SC). The VHA EMRs were linked to the US census which provided area-level factors. US census data were used to construct the Social Vulnerability Index which is a continuous composite measure of area-level vulnerability and was divided into tertiles for modeling purposes. Data were analyzed using a Bayesian multivariate conditional autoregressive model (CAR) which accounted for individual-level factors, area-level factors, spatial random effects, and autocorrelation, which were used to identify areas of higher- or lower-than-expected PrCA incidence after controlling for risk factors. As expected, after accounting for age (sixfold and 13-fold increases in men 40-50years and > 50years, respectively), race was an important risk factor, with threefold higher odds among Blacks in the fully adjusted model [ORadj 2.98 (2.77, 3.20)]. After accounting for all other factors, residing in a ZIP code tabulated areas (ZCTA) with the greatest level social vulnerability versus the lowest, least vulnerable ZCTA's, increased PrCA risk by 39% [ORadj 1.39 (1.11, 1.75)]. While accounting for known risk factors for PrCA, including age, race, and marital status, we found geographic areas in SC characterized by higher than average social vulnerability with higher rates of incident PrCA among veterans. Outreach for screening, education, and care coordination may be needed for veterans in these areas.

Germline and Somatic Mutations in Prostate Cancer for the Clinician.

It is increasingly important for clinicians involved in the management of prostate cancer to understand the relevance of heritable (germline) mutations that, for select patients, affect prostate cancer risk and cancer biology, and acquired (somatic) mutations that occur in prostate cancer cells. In the advanced disease setting, mutations in homologous recombination repair genes (eg, BRCA1, BRCA2, ATM, CHEK2, PALB2) suggest candidacy for platinum chemotherapy and PARP inhibitor trials. Similarly, microsatellite instability and mismatch repair deficiency, which may arise in the setting of MLH1, MSH2, MSH6, and PMS2 mutations, suggest potential vulnerability to PD-1 inhibitors. Germline genetic testing has potential importance in the treatment and assessment of familial risk, and tumor-directed somatic sequencing may guide treatment decision-making. This review provides clinicians with knowledge of basic genetic terminology, awareness of the importance of family history of cancer (not limited to prostate cancer), contrasts between the different but potentially related objectives of germline versus somatic testing of tumor tissue, and indications for genetic counseling. Specific clinical scenarios, objectives of testing, and nature of the assays are reviewed. Germline and somatic mutations of known and potential relevance to prostate cancer are discussed in the context of treatment options, and algorithms to assist clinicians in approaching this area are proposed.

Influence of lifestyle choices on risks of CYP1B1 polymorphisms for prostate cancer.

Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and how lifestyle choices may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population was analysed at polymorphic sites of the 5′ untranslated region of CYP1B1 using TaqMan genotyping assays. Overall, drinker status and minor alleles at rs2551188, rs2567206 and rs10175368 were associated with prostate cancer. Linkage was observed between rs2551188, rs2567206, rs2567207 and rs10175368, and the G‐C‐T‐G haplotype (major allele at respective sites) was decreased in cancer. Interestingly when classified by lifestyle factors, no associations of genotypes were found for non‐smokers and non‐drinkers, whereas on the contrary, minor type at rs2567206 and rs10175368 increased and major G‐C‐T‐G decreased risk for cancer among smokers and drinkers. Interestingly, rs2551188, rs2567206 and rs10175368 minor genotypes correlated with increased tissue CYP1B1 as determined by immunohistochemistry. Further, rs10175368 enhanced luciferase activity and mobility shift show stronger binding of nuclear factor for the minor allele. These results demonstrate smoking and alcohol consumption to modify the risks of CYP1B1 polymorphisms for prostate cancer which may be through rs10175368, and this is of importance in understanding their role in the pathogenesis and as a biomarker for this disease.

Testing of a Tool for Prostate Cancer Screening Discussions in Primary Care.

As prostate cancer (PCa) screening decisions often occur in outpatient primary care, a brief tool to help the PCa screening conversation in busy clinic settings is needed. A previously created 9-item tool to aid PCa screening discussions was tested in five diverse primary care clinics. Fifteen providers were recruited to use the tool for 4 weeks, and the tool was revised based upon feedback. The providers then used the tool with a convenience sample of patients during routine clinic visits. Pre- and post-visit surveys were administered to assess patients' knowledge of the option to be screened for PCa and of specific factors to consider in the decision. McNemar's and Stuart-Maxwell tests were used to compare pre-and post-survey responses. 14 of 15 providers completed feedback surveys and had positive responses to the tool. All 15 providers then tested the tool on 95 men aged 40-69 at the five clinics with 2-10 patients each. The proportion of patients who strongly agreed that they had the option to choose to screen for PCa increased from 57 to 72% (p = 0.018) from the pre- to post-survey, that there are factors in the personal or family history that may affect PCa risk from 34 to 47% (p = 0.012), and that their opinions about possible side effects of treatment for PCa should be considered in the decision from 47 to 61% (p = 0.009). A brief conversation tool for the PCa screening discussion was well received in busy primary-care settings and improved patients' knowledge about the screening decision.

A Prostate Cancer Risk Element Functions as a Repressive Loop that Regulates HOXA13

Prostate cancer (PCa) is the leading cancer among men in the United States, with genetic factors contributing to ∼42% of the susceptibility to PCa. We analyzed a PCa risk region located at 7p15.2 to gain insight into the mechanisms by which this noncoding region may affect gene regulation and contribute to PCa risk. We performed Hi-C analysis and demonstrated that this region has long-range interactions with the HOXA locus, located ∼873 kb away. Using the CRISPR/Cas9 system, we deleted a 4-kb region encompassing several PCa risk-associated SNPs and performed RNA-seq to investigate transcriptomic changes in prostate cells lacking the regulatory element. Our results suggest that the risk element affects the expression of HOXA13 and HOTTIP, but not other genes in the HOXA locus, via a repressive loop. Forced expression of HOXA13 was performed to gain further insight into the mechanisms by which this risk element affects PCa risk.

Abstract 2288: Effects of tobacco smoking and alcohol consumption on risks of CYP1B1 polymorphisms for prostate cancer

Abstract Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and polymorphic variants have been shown to increase activity levels. Lifestyle choices such as tobacco smoking and alcohol consumption are known to enhance the carcinogenesis process and in this study, how these factors may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. Blood genomic DNA from a Caucasian population consisting of 405 healthy men and 400 prostate cancer patients were obtained. Of these, 507 were current or former smokers and 407 were alcohol drinkers. Eight polymorphic sites of the promoter region of CYP1B1 (rs2551188 G to A, rs2567206 G to A, rs2567207 A to G, rs162556 A to G, rs10175368 C to T, rs163090 T to A, rs162330 T to G, and rs162331 A to G) were analyzed in samples using Taqman genotyping assays and real-time PCR. Lifestyle factors and its influence on CYP1B1 polymorphisms toward cancer risks were also evaluated. Overall, both alcohol (P=0.006) and smoker (P=0.069) status were associated with prostate cancer. CYP1B1 variants were also risks for cancer at rs2551188 (P=0.043), rs2567206 (P=0.008), and rs10175368 (P=0.001). Evaluation of linkage disequilibrium show rs2551188, rs2567206, rs2567207, and rs10175368 to be linked and interestingly, the G-G-A-C haplotype (wildtype at respective sites) was significantly reduced in cancer (P=0.0282). When classified by lifestyle factors, no associations for CYP1B1 variants were found for cancer among non-smokers with rs10175368 (P=0.051) being a risk among non-drinkers. On the other hand, variants at both rs2567206 and rs10175368 showed increased cancer risk among smokers (P=0.032 and 0.002, respectively) as well as drinkers (P=0.044 and 0.019, respectively). No genotyping differences were observed when analyzing cancers by pathological grades. These results demonstrate smoker and alcoholic drinker status to modify the risks of CYP1B1 polymorphisms for prostate cancer and this is of importance in understanding their role in the pathogenesis of this disease. Citation Format: Taku Kato, Yutaka Hashimoto, Shigekatsu Maekawa, Marisa Shiina, Mitsuho Imai-Sumida, Pritha Dasgupta, Priyanka Kulkarni, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Varahram Sharryari, Guoren Deng, Rajvir Dahiya, Yuichiro Tanaka. Effects of tobacco smoking and alcohol consumption on risks of CYP1B1 polymorphisms for prostate cancer [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 2288. doi:10.1158/1538-7445.AM2017-2288

MP14-06 RISKS OF CYTOCHROME P450 1B1 POLYMORPHISMS AND LIFESTYLE CHOICES ON PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Epidemiology & Natural History II1 Apr 2017MP14-06 RISKS OF CYTOCHROME P450 1B1 POLYMORPHISMS AND LIFESTYLE CHOICES ON PROSTATE CANCER Taku Kato, Yutaka Hashimoto, Shigekatsu Maekawa, Marisa Shiina, Mitsuho Imai-Sumida, Pritha Dasgupta, Priyanka Kulkarni, Soichiro Yamamura, Shahana Majid, Sharanjot Saini, Varahram Sharryari, Guoren Deng, Rajvir Dahiya, and Yuichiro Tanaka Taku KatoTaku Kato More articles by this author , Yutaka HashimotoYutaka Hashimoto More articles by this author , Shigekatsu MaekawaShigekatsu Maekawa More articles by this author , Marisa ShiinaMarisa Shiina More articles by this author , Mitsuho Imai-SumidaMitsuho Imai-Sumida More articles by this author , Pritha DasguptaPritha Dasgupta More articles by this author , Priyanka KulkarniPriyanka Kulkarni More articles by this author , Soichiro YamamuraSoichiro Yamamura More articles by this author , Shahana MajidShahana Majid More articles by this author , Sharanjot SainiSharanjot Saini More articles by this author , Varahram SharryariVarahram Sharryari More articles by this author , Guoren DengGuoren Deng More articles by this author , Rajvir DahiyaRajvir Dahiya More articles by this author , and Yuichiro TanakaYuichiro Tanaka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2017.02.470AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Cytochrome P450 1B1 (CYP1B1) converts xenobiotics to carcinogens and polymorphic variants have been shown to increase activity levels. Lifestyle choices such as tobacco smoking and alcohol consumption are known to enhance the carcinogenesis process and in this study, how these factors may interact with CYP1B1 polymorphisms and affect prostate cancer risk was assessed. METHODS Blood genomic DNA from a Caucasian population consisting of 405 healthy men and 400 prostate cancer patients were obtained. Of these, 507 were current or former smokers and 407 were alcohol drinkers. Eight polymorphic sites of the promoter region of CYP1B1 (rs2551188 G to A, rs2567206 G to A, rs2567207 A to G, rs162556 A to G, rs10175368 C to T, rs163090 T to A, rs162330 T to G, and rs162331 A to G) were analyzed in samples using Taqman genotyping assays and real-time PCR. Lifestyle factors and its influence on CYP1B1 polymorphisms toward cancer risks were also evaluated. RESULTS Overall, both alcohol (P=0.006) and smoker (P=0.069) status were associated with prostate cancer. CYP1B1 variants were also risks for cancer at rs2551188 (P=0.043), rs2567206 (P=0.008), and rs10175368 (P=0.001). Evaluation of linkage disequilibrium show rs2551188, rs2567206, rs2567207, and rs10175368 to be linked and interestingly, the G-G-A-C haplotype (wildtype at respective sites) was significantly reduced in cancer (P=0.0282). When classified by lifestyle factors, no associations for CYP1B1 variants were found for cancer among non-smokers with rs10175368 (P=0.051) being a risk among non-drinkers. On the other hand, variants at both rs2567206 and rs10175368 showed increased cancer risk among smokers (P=0.032 and 0.002, respectively) as well as drinkers (P=0.044 and 0.019, respectively). No genotyping differences were observed when analyzing cancers by pathological grades. CONCLUSIONS These results demonstrate smoker and alcoholic drinker status to modify the risks of CYP1B1 polymorphisms for prostate cancer and this is of importance in understanding their role in the pathogenesis of this disease. © 2017FiguresReferencesRelatedDetails Volume 197Issue 4SApril 2017Page: e164 Advertisement Copyright & Permissions© 2017MetricsAuthor Information Taku Kato More articles by this author Yutaka Hashimoto More articles by this author Shigekatsu Maekawa More articles by this author Marisa Shiina More articles by this author Mitsuho Imai-Sumida More articles by this author Pritha Dasgupta More articles by this author Priyanka Kulkarni More articles by this author Soichiro Yamamura More articles by this author Shahana Majid More articles by this author Sharanjot Saini More articles by this author Varahram Sharryari More articles by this author Guoren Deng More articles by this author Rajvir Dahiya More articles by this author Yuichiro Tanaka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate.

In parallel with the inconsistency in observational studies and chemoprevention trials, the mechanisms by which selenium affects prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled trial to examine the effects of a short-term intervention with selenium on gene expression in non-malignant prostate tissue. Twenty-three men received 300 μg selenium per day in the form of selenized yeast (n=12) or a placebo (n=11) during 5 weeks. Prostate biopsies collected from the transition zone before and after intervention were analysed for 15 participants (n=8 selenium, n=7 placebo). Pathway analyses revealed that the intervention with selenium was associated with down-regulated expression of genes involved in cellular migration, invasion, remodeling and immune responses. Specifically, expression of well-established epithelial markers, such as E-cadherin and epithelial cell adhesion molecule EPCAM, was up-regulated, while the mesenchymal markers vimentin and fibronectin were down-regulated after intervention with selenium. This implies an inhibitory effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium was associated with down-regulated expression of genes involved in wound healing and inflammation; processes which are both related to EMT. In conclusion, our explorative data showed that selenium affected expression of genes implicated in EMT in the transition zone of the prostate.

The emerging role of obesity, diet and lipid metabolism in prostate cancer.

Obesity is associated with an increased risk of a number of serious medical conditions, including cancer. As far as prostate cancer is concerned, obesity is associated with an increased risk of high-grade tumors, which is possibly related to lower androgen levels. Diet may also affect prostate cancer risk since countries with a higher dietary fat intake also present higher prostate cancer mortality rates. Interestingly, prostate cancer is associated with a number of metabolic alterations that may provide valuable diagnostic and therapeutic targets. This review explores the available clinical as well as biological evidence supporting the relationship between obesity, diet, alteration in metabolic pathways and prostate cancer.

Systematic enrichment analysis of potentially functional regions for 103 prostate cancer risk-associated loci.

More than 100 prostate cancer (PCa) risk-associated single nucleotide polymorphisms (SNPs) have been identified by genome wide association studies (GWAS). However, the molecular mechanisms are unclear for most of these SNPs. All reported PCa risk-associated SNPs reaching the genome-wide significance level of P < 1 × 10(-7) (index SNPs), as well as SNPs in linkage disequilibrium (LD, r(2) ≥ 0.5) with them were cataloged. Genomic regions with potentially functional impact were also identified, including UCSC annotated coding regions (exon and snoRNA/miRNA) and regulatory regions, as well as binding regions for transcription factors (TFs), histone modifications (HMs), DNase I hypersensitivity (DHSs), and RNA Polymerase IIA (POLR2A) defined by ChIP-Seq in prostate cell lines and tissues. Enrichment analysis was performed to test whether PCa risk-associated SNPs are located in these functional regions more than expected. A total of 103 PCa risk-associated index SNPs and 7,244 SNPs in LD with these index SNPs were cataloged. Genomic regions with potentially functional impact, grouped in 30 different categories of functionalities, were identified. Enrichment analysis indicated that genomic regions in the following 15 categories were enriched for the PCa risk-associated SNPs: exons, CpG regions, 6 TFs (AR, ERG, FOXA1, HOXB13, CTCF, and NR3C1), 5 HMs (H3K4me1, H3K4me2, H3K4me3, H3K27AC, and H3T11P), DHSs and POLR2A. In contrast, significantly fewer PCa risk SNPs were mapped to binding regions for H3K27me3, a repressive chromatin marker. The PCa risk-associated SNPs discovered to date may affect PCa risk through multiple different mechanisms, especially by affecting binding regions of TFs/HMs.

Both serum 25-hydroxyvitamin D and calcium levels may increase the risk of incident prostate cancer in Caribbean men of African ancestry.

Circulating 25-hydroxyvitamin D [25(OH)D] concentrations have been associated with both higher and lower risk of prostate cancer (PCa), whereas elevated levels of circulating calcium has been related to higher risks. However, there are few studies that account for effects of both calcium and 25(OH)D concentrations on incident PCa in a black population. We examined these relationships in a case–control study of men 40–80 years old with newly diagnosed, histologically confirmed PCa in Jamaica, a tropical country. Mean serum calcium concentrations was higher among cases (2.32 ± 0.19 mmol/L) than controls, (2.27 ± 0.30 mmol/L) (P = 0.023) however, there were no differences in 25(OH)D by cancer status (cases, 33.67 ± 12.71 ng/mL; controls (32.25 ± 12.59 ng/mL). Serum calcium was not correlated with 25(OH)D (partial correlation: r, 0.06; P = 0.287). Multivariable-adjusted models showed a positive linear relationship between PCa and serum calcium (OR, 1.12; CI, 1.00–1.25 per 0.1 nmol/L). Serum 25(OH)D concentration also showed a positive association with PCa (OR, 1.23; CI, 1.01–1.49 per 10 ng/mL). The odds of PCa in men with serum 25(OH)D tertile 2 was OR, 2.18; CI, 1.04–4.43 and OR, 2.47 CI, 1.20–4.90 for tertile 3 (Ptrend = 0.013). Dietary intakes of calcium showed no relationship with PCa. Despite the strong relationship between serum calcium and vitamin D the mechanism by which each affects prostate cancer risk in men of African ancestry needs additional investigation.