Prostate Cancer In Asian Population Research Articles

The Use of Soy Isoflavones in the Treatment of Prostate Cancer: A Focus on the Cellular Effects

A possible link between diet and cancer has long been considered, with growing interest in phytochemicals. Soy isoflavones have been associated with a reduced risk of prostate cancer in Asian populations. Of the soy isoflavones, genistein and daidzein, in particular, have been studied, but recently, equol as a derivative has gained interest because it is more biologically potent. Different mechanisms of action have already been studied for the different isoflavones in multiple conditions, such as breast, gastrointestinal, and urogenital cancers. Many of these mechanisms of action could also be demonstrated in the prostate, both in vitro and in vivo. This review focuses on the known mechanisms of action at the cellular level and compares them between genistein, daidzein, and equol. These include androgen- and estrogen-mediated pathways, regulation of the cell cycle and cell proliferation, apoptosis, angiogenesis, and metastasis. In addition, antioxidant and anti-inflammatory effects and epigenetics are addressed.

MO24-6 The incidence, mortality and clinical characteristic of metastatic hormone-sensitive prostate cancer in Asian population

There are notable differences in the incidence and mortality rates for prostate cancer between the Asians and Westerns. There is no data about the accurate number for the prevalence of mHSPC in Thailand. Our study aims to determine the prevalence, mortality, and clinical characteristics of mHSPC in the Thai population.

The Prostate Health Index and multi-parametric MRI improve diagnostic accuracy of detecting prostate cancer in Asian populations.

The aim of this study was to evaluate the effectiveness of the Prostate Health Index (PHI) and prostate multi-parametric magnetic resonance imaging (mpMRI) in predicting prostate cancer (PCa) and clinically significant prostate cancer (csPCa) during initial prostate biopsy. In total, 343 patients underwent initial prostate biopsy and were screened by use of PHI and prostate-specific antigen (PSA) levels between April 2019 and July 2021. A subgroup of 232 patients also underwent prostate mpMRI. Logistic regression analysis was performed to evaluate the accuracies of PSA, PHI, and mpMRI as predictors of PCa or csPCa. These predictive accuracies were quantified by using the area under the receiver operating characteristic curve. The different predictive models were compared using the DeLong test. Logistic regression showed that age, PSA, PHI, and prostate volume were significant predictors of both PCa and csPCa. In the mpMRI subgroup, age, PSA level, PHI, prostate volume, and mpMRI were predictors of both PCa and csPCa. The PHI (area under the curve [AUC]=0.693) was superior to the PSA level (AUC=0.615) as a predictor of PCa (p=0.038). Combining PHI and mpMRI showed the most accurate prediction of both PCa and csPCa (AUC=0.833, 0.881, respectively). The most accurate prediction of both PCa and csPCa can be performed by combining PHI and mpMRI. In the absence of mpMRI, PHI is superior to PSA alone as a predictor of PCa, and adding PHI to PSA can increase the detection rate of both PCa and csPCa.

Ethnicity as modifier of risk for Vitamin D receptors polymorphisms: Comprehensive meta-analysis of all cancer sites.

Vitamin D receptors polymorphisms are found to be associated with several cancers. Since their prevalence vary across ethnicities and ethnicity itself seems to influence the cancer risk, a comprehensive meta-analysis was performed to investigate the role of VDR Fok1, Bsm1, Taq1, Apa1, Cdx2 and cancer risk at specific organ sites. Odds ratios, calculated with random-effects models, summarized one-hundred-ninety-two independent studies for twenty-two cancer sites. Evidence was provided that Fok1, Bsm1, Cdx2, Apa1 and Taq1 are linked to cancer susceptibility for colorectal, lung, ovarian, skin, multiple myeloma and brain cancer. Stratifying by ethnicity, some differences were found, partially explained by minor allele frequency (MAF), for colorectal cancer, ovarian and prostate cancer in Caucasian and prostate cancer in Asian populations. In summary, ethnicity may be a modifier of cancer risk, in particular for hormone dependent cancers and it should be considered evaluating the effect of VDR on cancer risk.

A genomic and epigenomic atlas of prostate cancer in Asian populations.

Prostate cancer is the second most common cancer in men worldwide1. Over the past decade, large-scale integrative genomics efforts have enhanced our understanding of this disease by characterizing its genetic and epigenetic landscape in thousands of patients2,3. However, most tumours profiled in these studies were obtained from patients from Western populations. Here we produced and analysed whole-genome, whole-transcriptome and DNA methylation data for 208 pairs of tumour tissue samples and matched healthy control tissue from Chinese patients with primary prostate cancer. Systematic comparison with published data from 2,554 prostate tumours revealed that the genomic alteration signatures in Chinese patients were markedly distinct from those of Western cohorts: specifically, 41% of tumours contained mutations in FOXA1 and 18% each had deletions in ZNF292 and CHD1. Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression. Coding and noncoding mutations, as well as epimutations, converged on pathways that are important for prostate cancer, providing insights into this devastating disease. These discoveries underscore the importance of including population context in constructing comprehensive genomic maps for disease.

P066 - Clinical and pathologic characteristics of familial prostate cancer in Asian population

P066 - Clinical and pathologic characteristics of familial prostate cancer in Asian population

Clinical and pathologic characteristics of familial prostate cancer in Asian population.

We investigated prevalence of familial and hereditary prostate cancer (PCa) in Asian population, and compared clinical characteristics between familial and sporadic disease. Pedigrees of 1102 patients who were treated for PCa were prospectively acquired. Clinical and pathologic characteristics and biochemical recurrence (BCR)-free survival were compared between familial PCa and sporadic PCa in patients who underwent radical prostatectomy (RP; n = 751). The prevalence of familial, first-degree familial, and hereditary PCa was found to be 8.4%, 6.7%, and 0.9%, respectively; similar result was obtained in patients who underwent RP (8.4%, 6.4%, and 0.9%). Patients with familial PCa were significantly younger than those with sporadic PCa (63.3 vs 65.6 years; P = .015). However, preoperative variables (prostate-specific antigen, clinical stage, biopsy Gleason score [GS], and percentage of positive biopsy cores) and postoperative variables (surgical GS, upgrading rate, pathologic stage, and percentage of tumor volume) did not correlate with family history (P range: .114-.982). Kaplan-Meier analysis of 5-year BCR-free survival revealed no significant difference between sporadic (82.7%), familial (89.4%; P = .594), and first-degree familial (87.1%; P = .774) PCa. Analysis of p53, Bcl-2, Ki67, and other immunohistochemistry biomarkers revealed that only increasing p53 expression and first-degree familial PCa approached significance (P = .059). The prevalence of familial PCa was somewhat lower in the Asian population than in other ethnic groups. Clinical and pathologic variables and selected histologic biomarker abnormalities were not significantly different in patients with and without a family history of PCa. BCR-free survival following RP was also unaffected by family history.

The association between epididymo-orchitis and prostate cancer

To determine whether epididymo-orchitis, a common infectious disease among men, is associated with subsequent prostate cancer (PCa) via a nationwide cohort study.This nationwide population-based study of patients treated from 2001 to 2013 included a total of 4991 patients with epididymo-orchitis as the study group and 19,922 matched patients without epididymo-orchitis as a control group. We tracked the patients in both groups for a 5-year period to identify any new cases of PCa. Cox proportional hazards regressions were performed to calculate the hazard ratio (HR) of PCa during this 5-year follow-up period.Of the 24,913 patients in the study, 235 (0.9%) were newly diagnosed with PCa during the 5-year follow-up period; 77 (1.5%) of those were from the epididymo-orchitis group and 158 (0.8%) were from the control group. Compared to the patients without epididymo-orchitis, the adjusted HR for PCa for the patients with epididymo-orchitis was 1.56 (95% confidence interval [CI]: 1.18–2.06) during the 5-year follow-up period. Ages of more than 70 years, higher incomes, hypertension, and hyperlipidemia were more strongly associated withPCa in the study group than in the control group.The results were associated with a 56% increased risk for PCa among patients with epididymo-orchitis. Epididymo-orchitis may play an etiological role in the development of PCa in Asian populations. Further studies are warranted, however, to investigate the relationship between epididymo-orchitis and PCa.

Association of VDR gene TaqI polymorphism with the susceptibility to prostate cancer in Asian population evaluated by an updated systematic meta-analysis.

BackgroundThe vitamin D receptor (VDR) plays a key role in vitamin-mediated signaling pathway. Emerging evidence has suggested that the VDR polymorphism may contribute to the risk of prostate cancer (PCa). However, the existing results are not conclusive in Asian population.MethodsWe aim to evaluate the potential role of VDR polymorphisms on PCa of Asian population. PubMed, Scopus, Embase, Web of Science, Chinese National Knowledge Infrastructure, Wang Fang Data, and VIP Periodical were retrieved, and eligible studies (case–control or cohort study) meeting the inclusion criteria were evaluated through an updated meta-analysis using Stata13.0 software.ResultsA total of 1,363 cases and 2,101 controls obtained from 13 eligible publications were eventually included in this meta-analysis. Our results show that a significant association of VDR taq1 polymorphism with PCa risk, especially in the Japanese population. In the clinical stage-stratified analysis, the pooled results revealed no significant difference in genetic polymorphisms between the local stage and control groups, whereas there was increased frequency of T allele and TT genotype in the advanced tumor stage group compared with local tumor stage or control groups. Similarly, no significant difference was seen in Gleason <7 and control groups, but the T allele and TT genotype were significantly higher in the Gleason ≥7 group compared with Gleason <7 or control groups.ConclusionThe VDR TaqI polymorphism might be associated with PCa risk in Asian population, especially in the Japanese population. Also, PCa patients carrying the T allele or TT genotype were more likely to progress to advanced stage. These results suggest that VDR TaqI polymorphisms may be potential diagnostic biomarkers for PCa susceptibility.

Gonorrhea infection increases the risk of prostate cancer in Asian population: a nationwide population-based cohort study.

This nationwide population-based retrospective cohort study evaluated the risk of developing prostate cancer among patients with gonorrhea. We identified cases of newly diagnosed gonorrhea in men between 2000 and 2010 from the Taiwan National Health Insurance Research Database. Each patient with gonorrhea was matched to four controls, based on age and index year. All subjects were followed up from the index date to December 31, 2010. The Cox proportional hazards regression model was used to assess the risk of prostate cancer. A total of 355 men were included in the study group, and 1,420 age-matched subjects without gonorrhea were included in the control group. After adjusting for age, comorbidities, urbanization level, hospital level, and monthly income, gonorrhea was significantly associated with an increased risk of prostate cancer (adjusted hazard ratio = 5.66, 95% confidence interval = 1.36-23.52). Men aged 45-70years and those with lower monthly income were more strongly associated with prostate cancer in the study group than the control group. The higher risk for developing prostate cancer were also found in those without syphilis, without genital warts, without diabetes mellitus, without chronic obstructive pulmonary disease, without benign prostatic hypertrophy, without chronic prostatitis, and without alcoholism. The Kaplan-Meier analysis showed the risk of prostate cancer was significantly higher in the study group than in the control group. Gonorrhea may be involved in the development of prostate cancer. More intensive screening and prevention interventions for prostate cancer should be recommended in men with gonorrhea.

Association of glutathione S-transferase T1 and M1 polymorphisms with prostate cancer susceptibility in populations of Asian descent: a meta-analysis.

Genetic polymorphism was hypothesized to be reason of variation in prostate cancer incidence among different racial group. Based on that published data on the association of prostate cancer susceptibility with polymorphisms in genes encoding Glutathione S-transferases (GSTs) were inconclusive, the aim of this study was to more precisely address the role of GSTs polymorphisms (especially, GSTT1 and GSTM1 deletions) on prostate cancer risk in Asian descent. A meta-analysis including 8 articles with 711 cases and 1122 controls for GSTT1 and 1098 cases and 1588 controls for GSTM1 was performed. Significantly increased prostate cancer risk was found among subjects carrying GSTM1 null genotype (odds ratio (OR) = 1.403; 95% confidence interval (CI) = 1.088 - 1.808) but not among subjects carrying GSTT1 deletion genotype (OR = 0.959; 95%CI = 0.709 - 1.297). When stratified by country, the null genotype of GSTT1 neither increased nor decreased prostate cancer risk significantly in China (OR = 1.355; 95%CI = 0.895 - 2.049), Japan (OR = 0.812; 95%CI = 0.545 - 1.211), and Korea (OR = 1.056; 95%CI = 0.727 - 1.534). While significant association of elevated prostate cancer risk with GSTM1 deletion were found in China (OR = 1.665; 95%CI = 1.324 - .094) and Korea (OR = 1.914; 95%CI = 1.311 - 2.793) but not in Japan (OR = 0.980; 95%CI = 0.726 - 1.321). In summary, this meta-analysis suggested that the null genotype of GSTM1 rather than GSTT1 may be involved in the etiology of prostate cancer in Asian population.

Opportunities for targeted focal treatment in Japan.

Widespread prostate-specific antigen screening has led to an increase in prostate cancer diagnoses in Asian populations, reflecting changes in socioeconomic status and epidemiological features in these countries. In this setting, the present review explores opportunities for target focal therapy in Japan. Our review examines several topics relating to focal therapy in Asia, and discusses the current status of prostate cancer diagnosis and treatment in that region. First, we summarize the prevalence of prostate cancer in Asian populations. Second, we examine prostate cancer diagnosis and treatment options such as mapping biopsy and MRI fusion biopsy in Japan. Third, we review treatment strategies for localized prostate cancer, especially robotic-assisted surgery, active surveillance, and high-intensity focused ultrasound. Lastly, we discuss the potential for focal therapy in Japan. The number of localized prostate cancer patients is expected to increase in Asia. Accordingly, the need for precise diagnosis in terms of localization of prostate cancer foci will also expand. MRI fusion target biopsies are being performed in Asia, particularly in some Japanese academic institutions, but as pilot studies. In recent years, an increase in robotic-assisted surgery in East Asia has yielded new options in prostate cancer treatment. Although active surveillance is a practical choice for low-risk prostate cancer in some Asian countries, focal therapy is expected to see increasing interest as another alternative in Japan.

Meta-analysis of the Relation Between the VDR Gene TaqIpolymorphism and Genetic Susceptibility to Prostate Cancer in Asian Populations

Polymorphisms of the Taq I gene have been associated with prostate cancer risk. We applied a fixed-effects model to combine odds ratios (ORs) and 95% confidence intervals (95% CI). The Egger's test was carried out to evaluate potential publication bias. A total of 10 case-control studies enrolling 1,141 prostate cancer patients and 1,685 controls were included in this meta-analysis. Compared with the T allele, the OR for the C allele was 0.81 (0.70-0.94). The ORs for CT and CC+CT genotypes were 0.86 (0.74-1.01) and 0.84 (0.73-0.97) compared to wide type genotype (homozygote TT). The present meta-analysis suggests that the TF gene Taq I polymorphism may reduce the prostate cancer risk in Asian populations.

Abstract 583: Physiological concentrations of genistein reduced ER-α promoter methylation and increased ER-α expression in prostate cancer cells

Abstract Prostate cancer is the most common malignancy and the second leading cause of cancer death among men in the United States. The lower incidence and mortality rates of prostate cancer in Asian population were correlated to the high dietary consumption of isoflavone-rich soy. One of the most abundant and potent isoflavones in soy is genistein which has an estradiol like structure and high affinity to estrogen receptor-α (ER-α). It has been suggested that genistein exerts its anti-cancer effects through binding to ER-α, the later has anti-proliferative and pro-apoptotic effects in prostate cancer. ER-α is mainly expressed in prostate epithelial cells and is downregulated in localized prostate cancer with increasing grade from Prostatic Intraepithelial Neoplasia (PIN) through low to high Gleason grade. This expression pattern supports the notion of a tumor suppressor role of ER-α. Therefore, ER-α agonists may be potential chemopreventive and therapeutic agents for prostate cancer. One of the mechanisms by which ER-α is suppressed in prostate cancer is promoter methylation, the extent of which correlates with the ER-α expression level which in turn may be linked to the degree of aggressiveness of prostate cancer. We examined the effects of physiological range of genistein concentrations (0.5, 1, and 10µM) on ER-α promoter methylation and ER-α expression in LNCaP, LAPC-4, and PC-3 prostate cancer cells that exhibit various basal levels of ER-α expression. We demonstrated for the first time that genistein caused a significant dose-dependent reduction in ER-α promoter methylation in LNCaP and LAPC-4 cells, using methylation specific PCR. There was a corresponding dose-related increase in ER-α mRNA and protein levels in these two cell lines assayed by quantitative RT-PCR and immunoblotting, respectively. However, ER-α expression levels and ER-α promoter methylation were not changed in PC-3 cells, which could be attributed to the low basal level of ER-α promoter methylation and the high basal level of ER-α expression in this cell line. These findings suggest that physiological concentrations of genistein is capable of reactivating tumor suppressor pathways by reversing ER-α promoter methylation with a subsequent restoration of the level of ER-α expression in prostate cancer cells that have higher basal levels of methylation. (Supported in part by Grant No. CA116195) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 583. doi:1538-7445.AM2012-583

A novel androgen‐dependent prostate cancer xenograft model derived from skin metastasis of a Japanese patient

The incidence of, and mortality from, prostate cancer (PCa) has increased in Asian countries over the past decades, partly due to a change in dietary habits. Recent reports have revealed differences in the molecular basis of PCa among people of differing racial or ethnic backgrounds. PCa xenograft models established from Asian patients would be useful for understanding the basis of PCa in Asian populations; we therefore established and characterized a novel PCa xenograft model, JDCaP, from a metastatic skin lesion of a Japanese hormone-refractory prostate cancer (HRPC) patient. Skin metastatic tissue derived from poorly differentiated prostatic adenocarcinoma in a 61-year-old Japanese male was transplanted to nude mice and JDCaP was established by serial passage. Expression of androgen receptor (AR) and prostate-specific antigen (PSA) was evaluated by immunohistochemistry and the AR sequence was analyzed. Hormone sensitivity of JDCaP was investigated in vivo by orchiectomy followed by administration of steroid hormones, including testosterone, estradiol, progesterone, and hydrocortisone. Therapeutic effects of leuprorelin acetate, bicalutamide, flutamide, diethylstilbestrol (DES), and estradiol were investigated. JDCaP expressed wild-type AR and PSA and showed androgen dependence. Only testosterone administration maintained tumor proliferation after orchiectomy. Administration of leuprorelin acetate, bicalutamide, and flutamide inhibited tumor growth. DES and estradiol also demonstrated significant antitumor effects. JDCaP expresses wild-type ARs and exhibits androgen dependence despite its origin from a HRPC patient. The model may be useful to elucidate the molecular basis of PCa in Asian populations and to develop prevention and therapeutic strategies.

Prevalence of High-Grade Prostatic Intraepithelial Neoplasia in Prostate Gland of Korean Men: Comparisons Between Radical Prostatectomy and Cystoprostatectomy

Objectives To evaluate the prevalence of high-grade prostatic intraepithelial neoplasia (HGPIN) and its association with prostate cancer in Korean men. Methods A total of 160 patients who underwent radical prostatectomy for clinical prostate cancer were included as study subjects and 29 patients who underwent radical cystoprostatectomy for muscle-invasive bladder cancer were included as controls. Each intact prostate gland was serially sectioned at 3-mm intervals perpendicular to the posterior surface. The presence and prevalence of prostate cancer and HGPIN were assessed and their association evaluated. Results High-grade prostatic intraepithelial neoplasia was present in 81 (70.4%) of 115 patients who underwent radical prostatectomy and in 8 (27.6%) of 29 patients who underwent cystoprostatectomy. This difference was statistically significant ( P <0.001). Among the patients who underwent cystoprostatectomy, HGPIN was present in 5 (33.3%) of 15 patients with prostate cancer and in 3 (21.4%) of 14 patients with no evidence of prostate cancer. The presence of HGPIN had no correlation with prostate-specific antigen level, disease stage, tumor volume, grade, lymphovascular invasion, or surgical margin status. Conclusions The prevalence of HGPIN in Korean men with clinical prostate cancer was as great as that of Western men. Previous studies, and our results, had demonstrated a lower prevalence of HGPIN in Asian men who underwent cystoprostatectomy. The different prevalence of HGPIN found in incidental prostate cancer, between Asian and Western men, suggests that factors could be preventing the progression of prostate cancer or different characteristics of the prostate cancer in Asian populations.

Molecular Effects of the Isoflavonoid Genistein in Prostate Cancer

Differences in diet have been proposed to be at least partially responsible for the low rate of prostate cancer in Asian populations compared with men in Western countries. One of the compounds that occurs in a greater quantity in the Eastern diet is genistein, an isoflavonoid found in high concentrations in serum after ingestion of soy-rich foods. Extensive molecular studies have been performed to determine its potential health benefits. The mechanism of action of genistein is complex and includes several cellular pathways. In addition to its estrogenic and/or antiestrogenic activities, genistein has been reported to inhibit steroidogenesis and block several protein tyrosine kinases, including epidermal growth factor receptor and src tyrosine kinases. Moreover, it arrests the cell cycle, induces apoptosis, and has antiangiogenic and antimetastatic properties and antioxidant activity. Herein, we review the current literature on the molecular mechanisms of genistein in relation to its effects on prostate cancer cells.

Changing trends of prostate cancer in Asia

Although Asian people have the lowest incidence and mortality rates of prostate cancer in the world, these rates have risen rapidly in the past two decades in most Asian countries. Prostate cancer has become one of the leading male cancers in some Asian countries. In 2000, the age-adjusted incidence was over 10 per 100 000 men in Japan, Taiwan, Singapore, Malaysia, the Philippines and Israel. Although some of the increases may result from enhanced detection, much of the increased incidence may be associated with westernization of the lifestyle, with increasing obesity and increased consumption of fat. The differences in incidences between native Americans and Asian immigrants are getting smaller, reflecting a possible improvement of diagnostic efforts and changes of environmental risk factors in Asian immigrants. Nevertheless, the huge variations in incidences among ethnic groups imply that there are important genetic risk factors. The stage distributions of prostate cancer in Asian populations are still unfavorable compared to those of Western developed countries. However, a trend towards diagnosing cancer with more favorable prognosis is seen in most Asian countries. Both genetic and environmental risk factors responsible for elevated risks in Asian people are being identified, which may help to reduce prostate cancer incidence in a chemopreventive setting.

Chemopreventive potential of epigallocatechin gallate and genistein: evidence from epidemiological and laboratory studies

A wide array of antioxidative and anti-inflammatory substances derived from edible plants have been reported to possess chemopreventive and chemoprotective activities. Among the most extensively investigated and well-defined dietary chemopreventives are epigallocatechin gallate (EGCG), a principal antioxidant derived from green tea and genistein, a major pharmacologically active isoflavone widely present in soy products. Multiple lines evidence from epidemiologic studies indicate that frequent consumption of green tea is inversely associated with the risk of several types of human cancer, and studies with animal and in vitro cell culture models have revealed EGCG as a major chemopreventive ingredient of green tea. The lower frequencies of breast and prostate cancer in Asian population in general, compared to those in Western societies have been attributed to their consumption of relatively large amounts of soy products. Genistein, as a principal chemopreventive components of soy, exerts a wide array of chemopreventive activities in each stage of multistep carcinogenesis. The purpose of this review is to provide perspectives on the molecular basis of chemopreventive activities of EGCG and geneistein as representative functional food phytochemicals with emphasis on their ability to control intracellular signaling cascades responsible for regulating cell growth and differentiation.