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Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa.

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Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 [95% confidence interval (CI) 4.84–5.29] for men of European ancestry to 3.74 [95% CI 3.36–4.17] for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher [95% CI 2.14–2.22], and men of East Asian ancestry 0.73-times lower [95% CI 0.71–0.76], than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

The use of online course material is the approach adopted by most universities to support students' revision, and teachers usually have the responsibility for designing or uploading online materials on their own course websites. However, some teachers might lack programming skills or motivation, and most current online materials are just uploaded in a static format (such as PDF) which is not suitable for all students. Moreover, during revision periods students may be faced with a lot of unorganised materials to be revised in a short period of time, and this can lead to an ineffective revision process. In order to address these issues, this paper proposes a software framework that aims to maximise the benefit of current online materials when used to support student revision. This framework is called SRECMATs (Self-Revision E-Course MATerials) and has been deployed as a tool that allows teachers to automatically create an intelligent tutoring system to manage online materials without any programming knowledge, and to support students to navigate easily through these online materials during their revision. This paper evaluates the proposed framework in order to understand students' perceptions with regard to the use of the system prototype, and the results indicate which features are suitable for providing online revision materials as well as confirming the benefit of the revision framework.

when cancer prevalence increased, for overall cancer (r=-0.64, p<0.0001) and csPCa 20 (r=-0.75, p=0.032). Eight studies fulfilled the inclusion criteria for meta-analysis. 21Seven reported results for overall PCa. When the overall PCa prevalence increased 22 from 30% to 60%, the combined NPV estimates decreased from 88% (95% 23 confidence interval (95% CI), 77-99%) to 67% (95% CI, 56-79%) for a cut-off score 24 of 3/5. Only one study selected for meta-analysis reported results for Gleason ≥7 25 cancers, with a positive biopsy rate of 29.3%. The corresponding NPV for a cut-off 26 score of ≥3/5 was 87.9%. 27Conclusion: mpMRI NPV varied greatly depending on study design, cancer 28 prevalence, and definitions of positive mpMRI and csPCa. Because cancer 29 prevalence was highly variable among series, risk stratification of patients should be 30 the initial step before considering prebiopsy mpMRI and defining those in whom 31 biopsy may be omited when the mpMRI is negative.

Context. In men with prostate cancer (PCa) treated with curative intent, controversy exists regarding the impact of biochemical recurrence (BCR) on oncological patient outcomes. Objective. To perform a systematic review of the existing literature on BCR after treatment with curative intent for non-metastatic PCa. Objective 1 is to investigate whether oncological outcomes differ between patients with or without BCR. Objective 2 is to study which clinical factors and tumor features in patients with BCR have an independent prognostic impact on oncological outcomes. Evidence acquisition. Medline, Medline In-Process, Embase, and the Cochrane Central Register of Controlled Trials were searched. For objective 1, prospective and retrospective studies comparing survival outcomes of patients with or without BCR following radical prostatectomy (RP) or radical radiotherapy (RT) were included. For objective 2, all studies with at least 100 participants and reporting on prognostic features in patients with BCR were included. Risk-of-bias and confounding assessments were performed according to the Quality in Prognosis Studies (QUIPS) tool. Both a narrative synthesis and meta-analysis were undertaken. Evidence synthesis. Overall, 77 studies were included for analysis, of which 14 studies addressed objective 1, recruiting 20406 patients. Objective 2 was addressed by 71 studies with 29057, 11301 and 4272 patients undergoing RP, RT or a mixed population (mix of patients undergoing RP or RT as primary treatment) respectively. There was low risk of bias for study participation, confounders and statistical analysis. For most studies, attrition bias, prognostic and outcome measurements were not clearly reported. BCR was associated with worse survival rates, mainly in patients with a short PSA Doubling Time (PSA-DT) and high final Gleason score after RP or a short Interval to Biochemical Failure (IBF) after RT and high biopsy Gleason score. Conclusion. BCR has an impact on survival, but this effect appears to be limited to a subgroup of patients with specific clinical risk factors. A short PSA-DT and high final Gleason score after RP and a short IBF after RT and high biopsy Gleason score are the main factors which have a negative impact on survival. Patient summary. This review looks at the risk of dying in men who have a rising PSA blood test after curative surgery or radiotherapy. For many men a rising PSA does not mean they are at a higher risk of dying from prostate cancer in the longer term. Men with a PSA that rises shortly after they were treated with radiotherapy or a rapidly rising PSA after surgery and a high tumor-grade for both treatment modalities are at the highest risk of dying.