Displaying publications 41 - 60 of 112 in total

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  1. Ren X, Nur Salihin Yusoff M, Hartini Mohd Taib N, Zhang L, Wang K
    Eur J Radiol, 2024 Jan;170:111274.
    PMID: 38147764 DOI: 10.1016/j.ejrad.2023.111274
    PURPOSE: The goal of this study was to evaluate the effectiveness of two diagnostic methods, 68Ga-PSMA-11 PET/CT and mpMRI, in detecting primary prostate cancer without limitations on the Gleason score.

    METHODS: We conducted a comprehensive literature review, searching databases such as PubMed, Embase, and Web of Science until June 2023. Our objective was to identify studies that compared the efficacy of 68Ga-PSMA-11 PET/CT and mpMRI in detecting primary prostate cancer. To determine heterogeneity, the I2 statistic was used. Meta-regression analysis and leave-one-out sensitivity analysis were conducted to identify potential sources of heterogeneity.

    RESULTS: Initially, 1286 publications were found, but after careful evaluation, only 16 studies involving 1227 patients were analyzed thoroughly. The results showed that the 68Ga-PSMA-11 PET/CT method had a pooled sensitivity and specificity of 0.87 (95 % CI: 0.80-0.92) and 0.80 (95 % CI: 0.69-0.89), respectively, for diagnosing prostatic cancer. Similarly, the values for mpMRI were determined as 0.84 (95 % CI: 0.75-0.92) and 0.74 (95 % CI: 0.61-0.86), respectively. There were no significant differences in diagnostic effectiveness observed when comparing two primary prostate cancer methodologies (pooled sensitivity P = 0.62, pooled specificity P = 0.50). Despite this, the funnel plots showed symmetry and the Egger test results (P values > 0.05) suggested there was no publication bias.

    CONCLUSIONS: After an extensive meta-analysis, it was found that both 68Ga-PSMA-11 PET/CT and mpMRI demonstrate similar diagnostic effectiveness in detecting primary prostate cancer. Future larger prospective studies are warranted to investigate this issue further.

    Matched MeSH terms: Prostate
  2. Bancroft EK, Page EC, Castro E, Lilja H, Vickers A, Sjoberg D, et al.
    Eur Urol, 2014 Sep;66(3):489-99.
    PMID: 24484606 DOI: 10.1016/j.eururo.2014.01.003
    BACKGROUND: Men with germline breast cancer 1, early onset (BRCA1) or breast cancer 2, early onset (BRCA2) gene mutations have a higher risk of developing prostate cancer (PCa) than noncarriers. IMPACT (Identification of Men with a genetic predisposition to ProstAte Cancer: Targeted screening in BRCA1/2 mutation carriers and controls) is an international consortium of 62 centres in 20 countries evaluating the use of targeted PCa screening in men with BRCA1/2 mutations.

    OBJECTIVE: To report the first year's screening results for all men at enrollment in the study.

    DESIGN, SETTING AND PARTICIPANTS: We recruited men aged 40-69 yr with germline BRCA1/2 mutations and a control group of men who have tested negative for a pathogenic BRCA1 or BRCA2 mutation known to be present in their families. All men underwent prostate-specific antigen (PSA) testing at enrollment, and those men with PSA >3 ng/ml were offered prostate biopsy.

    OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA levels, PCa incidence, and tumour characteristics were evaluated. The Fisher exact test was used to compare the number of PCa cases among groups and the differences among disease types.

    RESULTS AND LIMITATIONS: We recruited 2481 men (791 BRCA1 carriers, 531 BRCA1 controls; 731 BRCA2 carriers, 428 BRCA2 controls). A total of 199 men (8%) presented with PSA >3.0 ng/ml, 162 biopsies were performed, and 59 PCas were diagnosed (18 BRCA1 carriers, 10 BRCA1 controls; 24 BRCA2 carriers, 7 BRCA2 controls); 66% of the tumours were classified as intermediate- or high-risk disease. The positive predictive value (PPV) for biopsy using a PSA threshold of 3.0 ng/ml in BRCA2 mutation carriers was 48%-double the PPV reported in population screening studies. A significant difference in detecting intermediate- or high-risk disease was observed in BRCA2 carriers. Ninety-five percent of the men were white, thus the results cannot be generalised to all ethnic groups.

    CONCLUSIONS: The IMPACT screening network will be useful for targeted PCa screening studies in men with germline genetic risk variants as they are discovered. These preliminary results support the use of targeted PSA screening based on BRCA genotype and show that this screening yields a high proportion of aggressive disease.

    PATIENT SUMMARY: In this report, we demonstrate that germline genetic markers can be used to identify men at higher risk of prostate cancer. Targeting screening at these men resulted in the identification of tumours that were more likely to require treatment.

    Matched MeSH terms: Prostate/pathology*; Prostate-Specific Antigen/blood*
  3. Heidari MH, Porghasem M, Mirzaei N, Mohseni JH, Heidari M, Azargashb E, et al.
    J Environ Radioact, 2014 Feb;128:64-7.
    PMID: 24292395 DOI: 10.1016/j.jenvrad.2013.11.001
    Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p 
    Matched MeSH terms: Prostate-Specific Antigen/blood*
  4. Hall SK, Ooi EH, Payne SJ
    Crit Rev Biomed Eng, 2014;42(5):383-417.
    PMID: 25745803
    Minimally invasive tumor ablations (MITAs) are an increasingly important tool in the treatment of solid tumors across multiple organs. The problems experienced in modeling different types of MITAs are very similar, but the development of mathematical models is mostly performed in isolation according to modality. Fundamental research into the modeling of specific types of MITAs is indeed required, but to choose the optimal treatment for an individual the primary clinical requirement is to have reliable predictions for a range of MITAs. In this review of the mathematical modeling of MITAs 4 modalities are considered: radiofrequency ablation, microwave ablation, cryoablation, and irreversible electroporation. The similarities in the mathematical modeling of these treatments are highlighted, and the analysis of the models within a general framework is discussed. This will aid in developing a deeper understanding of the sensitivity of MITA models to physiological parameters and the impact of uncertainty on predictions of the ablation zone. Through robust validation and analysis of the models it will be possible to choose the best model for a given application. This is important because many different models exist with no objective comparison of their performance. The collection of relevant in vivo experimental data is also critical to parameterize such models accurately. This approach will be necessary to translate the field into clinical practice.
    Matched MeSH terms: Prostate/surgery
  5. Wong PF, Abubakar S
    J Trace Elem Med Biol, 2008;22(3):242-7.
    PMID: 18755400 DOI: 10.1016/j.jtemb.2008.03.008
    Prostate cancer is an age-related disease that is linked to the inability of prostate cells to accumulate zinc following transformation. It is shown in the present study that the basal percentage of normal prostate cells expressing senescence-associated beta-galactosidase (SA-beta-gal) is higher than that of the cancer cells. In the presence of high zinc in the cell culture medium, the percentage of normal prostate cells expressing the SA-beta-gal increased but not that of the cancer cells. Increased intracellular zinc occurs in the prostate cancer cells treated with supraphysiologic concentration of zinc but it does not induce senescence or decrease the telomerase activities in these cells. Senescence, however, occurred when the prostate cancer cells DNA is damaged by irradiation. These findings suggest that prostate cancer cells are insensitive to the senescence-inducing effects of zinc but the cancer cells retain the capacity to undergo senescence through other pathways.
    Matched MeSH terms: Prostate/drug effects
  6. Karuppaiya A, Cheah SH, Mohd S, Kamal WH, Zulkifli MH
    Hybridoma (Larchmt), 2009 Apr;28(2):133-7.
    PMID: 19249990 DOI: 10.1089/hyb.2008.0085
    Prostate-specific antigen (PSA) is widely used as a diagnostic marker for the detection of prostate cancer in men. We have generated stable hybridomas producing specific monoclonal antibodies (MAbs) of the IgG class against PSA from fusions of splenocytes from immunized mice with myeloma cells. The hybridomas were adapted into serum-free media and cultured in CELLine CL-1000 bioreactors to produce milligram quantities of MAbs. Cross-reactivity study demonstrated that all the MAbs reacted did not cross-react with several other types of tumor antigens. Two of the MAbs were successfully radiolabeled by the iodogen method. The (125)I-labeled MAbs demonstrated strong binding to PSA on the surface of the LNCaP cells (Kd of 1.16 x 10(-9) M and 1.4 x 10(-9) M). Thus the (125)I-labeled MAbs retained their immunoreactivity and possessed high affinity and is potentially useful for binding to tumor cells. In conclusion, the MAbs can be used to develop radioimmunodiagnostic, radioimaging, and immunohistochemistry techniques for the early detection and treatment of prostate cancer.
    Matched MeSH terms: Prostate-Specific Antigen/immunology*
  7. Lim J, Bhoo-Pathy N, Sothilingam S, Malek R, Sundram M, Tan GH, et al.
    PLoS One, 2015;10(6):e0130820.
    PMID: 26098884 DOI: 10.1371/journal.pone.0130820
    To determine the lower urinary tract symptoms (LUTS) profile and factors affecting its degree of severity including cardiovascular risk profile, age, ethnicity, education level and prostate volume in a multiethnic Asian setting.
    Matched MeSH terms: Prostate/pathology
  8. Dublin N, Razack AH, Loh CS
    ANZ J Surg, 2001 Jun;71(6):384-5.
    PMID: 11409027
    Matched MeSH terms: Transurethral Resection of Prostate/adverse effects*
  9. Quek KF, Low WY, Razack AH, Loh CS
    BJU Int, 2001 Jul;88(1):21-5.
    PMID: 11446839
    OBJECTIVE: To validate the English version of the International Prostate Symptom Score (IPSS) in patients with and without urinary symptoms in a Malaysian population.

    PATIENTS AND METHODS: Validity and reliability were assessed in patients with lower urinary tract symptoms (LUTS) and in patients with no LUTS. Reliability was evaluated using the test-retest method and internal consistency using Cronbach's alpha. Sensitivity to change was expressed as the effect size in the score before and after intervention in additional patients with LUTS who underwent transurethral resection of the prostate (TURP).

    RESULTS: Internal consistency was excellent; there was a high degree of internal consistency for each of the seven domains and for the total score (Cronbach's alpha > or = 0.60 and > or = 0.79, respectively) in the populations studied. The test-retest correlation coefficient for the seven domain scores was highly significant. The intra-class correlation coefficient was high (> or = 0.59). There was a high level of sensitivity and specificity for the effects of treatment, with a very significant change between the seven scores domains in the treated group but not in the control group.

    CONCLUSIONS: The IPSS is suitable, reliable, valid and sensitive to clinical change in the Malaysian population.

    Matched MeSH terms: Transurethral Resection of Prostate/methods
  10. Quek KF, Chua CB, Low WY, Razack AH, Loh CS
    BJU Int, 2002 Jul;90(1):37-40.
    PMID: 12081766
    OBJECTIVE: To validate the Malay version of the Health-Related Quality of Life (Mal-HRQOL-20) questionnaire in patients with and without urinary symptoms in a Malaysian population.

    PATIENTS AND METHODS: The validity and reliability of the Mal-HRQOL-20 were assessed in patients with and without lower urinary tract symptoms (LUTS). The reliability was evaluated using the test-retest method and the internal consistency using Cronbach's alpha. Sensitivity to change was expressed as the effect size in the score before and after intervention in additional patients with LUTS who underwent transurethral resection of the prostate.

    RESULTS: The internal consistency was excellent; there was a high degree of internal consistency for each of the 20 items and for the overall score (Cronbach's alpha > or = 0.57 and 0.79, respectively) in the population study. The test-retest correlation coefficient for the 20 item scores was highly significant. The intra-class correlation coefficient was high (> or = 0.55). The sensitivity and specificity were high for the effects of treatment. There was a very significant agreement between scores before and after treatment across all domains in the treatment cohort, but not in the control group.

    CONCLUSION: The Mal-HRQOL-20 is suitable, reliable, valid and sensitive to clinical change in the Malaysian population.

    Matched MeSH terms: Transurethral Resection of Prostate/psychology
  11. Quek KF, Low WY, Razack AH, Loh CS
    BJU Int, 2000 Oct;86(6):630-3.
    PMID: 11069367
    OBJECTIVE: To assess and evaluate the level of depression, anxiety and psychiatric status in patients with lower urinary tract symptoms (LUTS) before and after treatment by surgery or drugs.

    PATIENTS AND METHODS: The study included 123 patients (mean age 64.6 years, SD 7. 95) with LUTS who were treated medically (with alpha-blockers, i.e. terazosin, prazosin, doxazosin and alfuzosin), and 52 patients (mean age 69.6 years, SD 7.94) with LUTS and confirmed to have benign prostatic hyperplasia (BPH) who underwent transurethral resection of the prostate (TURP). Both groups were assessed at baseline and 3 months after treatment using standardized questionnaires (the Beck Depression Inventory, the State-Trait Anxiety Inventory and the General Health Questionnaire-12).

    RESULTS: Patients before TURP were significantly more depressed, worried and psychiatrically morbid than were those before medical treatment. Three months after medical and surgical treatment, there was significantly less depression, anxiety and psychiatric morbidity in the TURP than in the medication group.

    CONCLUSIONS: TURP is a better treatment than medication for minimising anxiety, depression and psychiatric morbidity after treatment in patients with LUTS, but causes greater psychological stress before treatment.

    Matched MeSH terms: Transurethral Resection of Prostate/psychology
  12. Chong WL, Sahabudin RM, Teh GC, Woo SYY, Lim TC, Khairullah A
    Med J Malaysia, 2001 Jun;56(2):167-73.
    PMID: 11771076
    DRE has been used as a diagnostic and screening tool for prostate cancer for decades. However these are based on Western data and its local applicability has yet to be verified. We held a Prostate Health Awareness Week in August 1998 and a total of 2086 men were screened. All men aged 50 years old and above were included for the study. The subjects were evaluated on DRE findings, PSA levels and if indicated a TRUS-guided biopsy results. We concluded that DRE per se might have limited role in the screening of prostate cancer in Malaysia. Screening using DRE and PSA combined are still recognized as the most cost-effective means. Neither DRE nor PSA alone has high enough specificity for diagnosis of prostate cancer cases. Combining DRE and PSA will definitely increase the specificity significantly.

    Study site: e Urology
    Clinic of Kuala Lumpur Hospital
    Matched MeSH terms: Prostate-Specific Antigen/blood
  13. Liong ML, Suzuki T, Yamanaka H, Kurokawa K, Daikuzono N, Nakazato M
    J Clin Laser Med Surg, 1994 Apr;12(2):85-92.
    PMID: 10151050
    Prostalase¿ has a probe that emits a laser beam at 360 degrees . Targeted obstructive prostatic adenoma tissue was heated to above the cytotoxic threshold temperature of 45 degrees C. After successful canine prostate study, from September 1992 to April 1993, 45 patients were treated. This paper reports the 9 months results of this initial cohort of patients. Prostatic and periprostatic temperature mapping showed the mean temperature within the adenoma zone was 49 degrees C, while the periprostatic tissue remained within the safety level of less than 42.5 degrees C. The mean prostate volume reductions at 3, 6, and 9 months were 36, 33, and 38%, respectively. Those patients whose surgery was unsuccessful had prostatic tissue removed by TURP at 2 to 3 months. This tissue revealed a definite zone of coagulative necrosis. For the clinical assessment, patients were divided into urine retention (UR) and nonretention (NR) subgroups. At 9 months, 20 of the 32 UR subgroup and 10 of the 13 NR subgroup patients were available for assessment. Due to poor response or complications, 6 of the 26 UR patients (23%) required ancillary treatment. Hence, 20 of the 26 cases (77%) remained catheter free and their mean maximum uroflow +/- SE was 9.6 +/- 0.7 ml/sec. Based on a Siroky normogram only 7 of these 26 patients (27%) became unobstructed. Two of the 12 NR subgroup patients (17%) required ancillary treatment. The mean maximum uroflow +/- SE was 10.7 +/- 1.2 ml/sec.(ABSTRACT TRUNCATED AT 250 WORDS)
    Matched MeSH terms: Prostate/anatomy & histology
  14. Mariappan P, Chong WL, Sundram M, Mohamed SR
    BJU Int, 2004 Aug;94(3):307-10.
    PMID: 15291857
    To determine if a volume-adjusted increase in the number of biopsy cores could detect more prostate cancers than the standard sextant biopsy alone, without increasing morbidity, and to determine its applicability in Malaysian patients, as a standard sextant biopsy misses 20-25% of prostate malignancies.
    Matched MeSH terms: Prostate/pathology*
  15. Quek KF, Razack AH, Chua CB, Low WY, Loh CS
    Med J Malaysia, 2003 Dec;58(5):735-42.
    PMID: 15190661
    The aim of this study was to assess the effects of treating lower urinary tract symptoms (LUTS) on the quality of sexual function in a one-year follow up. A total of 116 patients with LUTS received alpha-blocker treatment, 111 patients underwent transurethral resection of the prostate (TURP) and 70 patients with renal stones, with no or mild symptoms served as a control group. The patients were assessed at baseline, three months, six months and twelve months using the International Index of Erectile Function (IIEF-15). The surgical group exhibited some changes in the domain of IIEF-15. Patients in the medical group showed improvement in erectile function and intercourse satisfaction, while orgasmic, overall sexual satisfaction and sexual drive were relatively unchanged. In contrast, the surgical group suffered retrograde ejaculation and overall sexual dissatisfaction after undergoing TURP. TURP has been found to be associated with retrograde ejaculation intercourse and overall sexual dissatisfaction.
    Matched MeSH terms: Transurethral Resection of Prostate*
  16. Yii RSL, Lim J, Sothilingam S, Yeoh WS, Fadzli AN, Ong TA, et al.
    Asian J Surg, 2020 Jan;43(1):87-94.
    PMID: 30962017 DOI: 10.1016/j.asjsur.2019.02.014
    OBJECTIVES: To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml.

    METHODS: Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis.

    RESULTS: A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p 

    Matched MeSH terms: Prostate-Specific Antigen/blood*
  17. Tun Firzara AM, Ng CJ
    BMJ Open, 2016 Sep 29;6(9):e011467.
    PMID: 27687897 DOI: 10.1136/bmjopen-2016-011467
    OBJECTIVE: Screening for prostate cancer remains controversial. General practitioners (GPs) play an important role in assisting men to make an informed decision on prostate cancer screening. The aim of this study was to determine the knowledge and practice of prostate cancer screening among private GPs in Malaysia.
    DESIGN: A cross-sectional study.
    SETTING: Private general practices in Selangor, Malaysia.
    PARTICIPANTS: 311 randomly selected full-time private GPs were recruited between September 2013 and January 2014.
    OUTCOME MEASURES: Questionnaires were distributed to the GPs via postal mail and clinic visits. The main outcomes were: knowledge of prostate cancer risk factors and screening tests; GPs' prostate cancer screening practices; and factors influencing GPs' decision to screen for prostate cancer. Associations between covariates and propensity to screen for prostate cancer were determined using logistic regression.
    RESULTS: The response rate was 65%. The proportion of GPs who overestimated the positive predictive values of prostrate-specific antigen (PSA), digital rectal examination (DRE) and a combination of PSA and DRE was 63%, 57% and 64%, respectively. About 49.5% of the respondents would routinely screen asymptomatic men for prostate cancer; of them, 94.9% would use PSA to screen. Male GPs who would consider having a PSA test performed on themselves were six times more likely to screen asymptomatic men than GPs who would not have the test (OR=6.88, 95% CI 1.40 to 33.73), after adjusting for age and duration of practice.
    CONCLUSIONS: GPs overestimated the accuracy of PSA in prostate cancer screening. Their intention to screen for prostate cancer themselves predicted their propensity to screen their patients for prostate cancer. This finding highlights the potential of using a new approach to change GPs' screening practices via addressing GPs' own screening behaviour.
    KEYWORDS: PREVENTIVE MEDICINE; PRIMARY CARE
    Matched MeSH terms: Prostate-Specific Antigen*
  18. Lim J, Rampal S, Razack AHA, Malek R, Sundram M, Nasuha NA, et al.
    Urology, 2018 Aug;118:145-151.
    PMID: 29746873 DOI: 10.1016/j.urology.2018.02.055
    OBJECTIVES: To develop a simple prostate volume (PV) calculator that can aid in managing patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic enlargement at daily urology services in developing Asian countries.

    MATERIALS AND METHODS: We conducted a cross-sectional study of men aged above 40 years with no history of prostate cancer, prostate surgery, or 5α-reductase inhibitor treatment. Serum prostate-specific antigen (PSA) and total PV were measured in each subject. Potential sociodemographic and clinical variables including age, weight, comorbidities, and International Prostate Symptom Score (IPSS) were collected. Of 1034 subjects, 837 were used in building the PV calculator using regression analysis. The remaining 1/5 (n = 197) was used for model validation.

    RESULTS: There were 1034 multiethnic Asian men (Chinese 52.9%, Malay 35.4%, and Indian 11.7%) with mean age of 60 ± 7.6 years. Average PV was 29.4 ± 13.0 mL while the overall mean of PSA was 1.7 ± 1.7 ng/mL. We identified age, IPSS, weight, and PSA (all P 

    Matched MeSH terms: Prostate/pathology*
  19. Awang A, Md Isa N, Yunus R, Azhar Shah S, Md Pauzi SH
    Malays J Pathol, 2019 Dec;41(3):253-257.
    PMID: 31901909
    INTRODUCTION: Gleason scoring (GS) categorised prostatic adenocarcinoma into five prognostic grade groups (PGGs); associated with different prognosis and treatment. This study aims to correlate between Gleason scores of needle biopsies with the corresponding total prostatectomy specimens, and to assess the relationship between the percentage of Gleason 4 tumour pattern (GP4) within Gleason score 7 (GS7) needle biopsy groups with the pathological staging.

    MATERIALS AND METHODS: Seventy-eight specimens of needle prostate biopsy and its subsequent radical prostatectomy were retrospectively studied. The GSs of the needle biopsy were compared with the corresponding prostatectomy specimens. The percentage of GP4 in GS7 needle biopsy groups was calculated and correlated with the pathological staging.

    RESULTS: More than half (60%) of GS 6 needle biopsy cases (PGG 1) were upgraded in the prostatectomy specimen, while the majority (80%) of the GS7 needle biopsy groups (PGG 2 and 3) remain unchanged. Cohen's Kappa shows fair agreement in the Gleason scoring between needle biopsies and prostatectomy specimens, K = 0.324 (95% CI, 6.94 to 7.29), p <0.0005 and in the percentage of GP4 in GS7 needle biopsy groups and their corresponding radical prostatectomy specimens, K = 0.399 (95% CI 34.2 - 49.2), p<0.0005. A significant relationship was seen between the percentage of GP4 in GS7 needle biopsy with the pT and pN stage of its radical prostatectomy (p = 0.008 and p=0.001 respectively).

    CONCLUSION: A higher percentage of GP4 in GS7 tumour is associated with worse tumour behaviour, therefore it is crucial for clinicians to realise this in deciding the optimal treatment.

    Matched MeSH terms: Prostate/pathology*
  20. Adams CD, Richmond R, Ferreira DLS, Spiller W, Tan V, Zheng J, et al.
    Cancer Epidemiol Biomarkers Prev, 2019 Jan;28(1):208-216.
    PMID: 30352818 DOI: 10.1158/1055-9965.EPI-18-0079
    BACKGROUND: Whether associations between circulating metabolites and prostate cancer are causal is unknown. We report on the largest study of metabolites and prostate cancer (2,291 cases and 2,661 controls) and appraise causality for a subset of the prostate cancer-metabolite associations using two-sample Mendelian randomization (MR).

    METHODS: The case-control portion of the study was conducted in nine UK centers with men ages 50-69 years who underwent prostate-specific antigen screening for prostate cancer within the Prostate Testing for Cancer and Treatment (ProtecT) trial. Two data sources were used to appraise causality: a genome-wide association study (GWAS) of metabolites in 24,925 participants and a GWAS of prostate cancer in 44,825 cases and 27,904 controls within the Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium.

    RESULTS: Thirty-five metabolites were strongly associated with prostate cancer (P < 0.0014, multiple-testing threshold). These fell into four classes: (i) lipids and lipoprotein subclass characteristics (total cholesterol and ratios, cholesterol esters and ratios, free cholesterol and ratios, phospholipids and ratios, and triglyceride ratios); (ii) fatty acids and ratios; (iii) amino acids; (iv) and fluid balance. Fourteen top metabolites were proxied by genetic variables, but MR indicated these were not causal.

    CONCLUSIONS: We identified 35 circulating metabolites associated with prostate cancer presence, but found no evidence of causality for those 14 testable with MR. Thus, the 14 MR-tested metabolites are unlikely to be mechanistically important in prostate cancer risk.

    IMPACT: The metabolome provides a promising set of biomarkers that may aid prostate cancer classification.

    Matched MeSH terms: Prostate-Specific Antigen/blood
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