Prediction of clinically significant prostate cancer using polygenic risk models in Asians.

PURPOSE: To develop and evaluate the performance of a polygenic risk score (PRS) constructed in a Korean male population to predict clinically significant prostate cancer (csPCa). MATERIALS AND METHODS: Total 2,702 PCa samples and 7,485 controls were used to discover csPCa susceptible single nucleotide polymorphisms (SNPs). Males with biopsy-proven or post-radical prostatectomy Gleason score 7 or higher were included for analysis. After genotype imputation for quality control, logistic regression models were applied to test association and calculate effect size. Extracted candidate SNPs were further tested to compare predictive performance according to number of SNPs included in the PRS. The best-fit model was validated in an independent cohort of 311 cases and 822 controls. RESULTS: Of the 83 candidate SNPs with significant PCa association reported in previous literature, rs72725879 located in PRNCR1 showed the highest significance for PCa risk (odds ratio, 0.597; 95% confidence interval [CI], 0.555-0.641; p=4.3×10-45). Thirty-two SNPs within 26 distinct loci were further selected for PRS construction. Best performance was found with the top 29 SNPs, with AUC found to be 0.700 (95% CI, 0.667-0.734). Males with very-high PRS (above the 95th percentile) had a 4.92-fold increased risk for csPCa. CONCLUSIONS: Ethnic-specific PRS was developed and validated in Korean males to predict csPCa susceptibility using the largest csPCa sample size in Asia. PRS can be a potential biomarker to predict individual risk. Future multi-ethnic trials are required to further validate our results.

Quantitative and qualitative evaluation on the accuracy of three intraoral scanners for human identification in forensic odontology.

The purpose of this study was to analyze the accuracy of intra oral scanner (IOS) to confirm the applicability of IOS for the recording and analysis of tooth morphology in forensics. The less damaged mandible specimen with many teeth remaining was scanned three times using three types of intraoral scanners (CS3600, i500, and Trios3). For quantitative comparisons of the scanned images produced by these intraoral scanners, root mean square (RMS) values were computed using a three-dimensional analysis program and a one-way ANOVA was conducted with Tukey HSD (honestly significant difference) as a post-hoc analysis (α=0.05). The repeatability of the full scan data was highest with the i500 (0.14±0.03 mm), and the post-hoc analysis confirmed significant differences between the CS3600 and the i500 outcomes (P-value=0.003). The repeatability of the partial scan data for the teeth in the mandible was highest with the i500 (0.08±0.02 mm), and the post-hoc analysis confirmed significant differences between the CS3600 and the i500 (P-value=0.016). The precision of the full scan data was highest with the i500 (0.16±0.01 mm) but the differences were not statistically significant (P-value=0.091). Meanwhile, the precision of the partial scan data for the teeth in the mandible was highest with the Trios3 (0.22±0.02 mm), but the differences were not statistically significant (P-value=0.762). Considering that the scanning of other areas of the oral cavity in addition to the teeth is important in forensic odontology, the i500 scanner appears to be the most appropriate intraoral scanner for human identification. However, as the scope of oral scanning is generally limited to teeth in the practice of dentistry, additional discussions of how to apply the IOS in forensic odontology are needed. Ultimately, the results here can contribute to the overall discussion of the forensic applicability dental data produced by intraoral scanners.

Evaluation of Polygenic Risk Scores for Prediction of Prostate Cancer in Korean Men.

AIMS: The purpose of this study is to evaluate an aggregate influence of prostate cancer (PCa) susceptibility variants on the development of PCa in Korean men by using the polygenic risk score (PRS) approach. METHODS: An analysis of 1,001 cases of PCa and 2,641 controls was performed to: (i) identify potential PCa-related risk loci in Koreans and (ii) validate the cumulative association between these loci and PCa using the PRS. Subgroup analyses based on risk stratification were conducted to better characterize the potential correlation to key PCa-related clinical outcomes (e.g., Gleason score, prostate-specific antigen levels). The results were replicated using 514 cases of PCa and 548 controls from an independent cohort. RESULTS: Genome-wide association analysis from our discovery cohort revealed 11 candidate single-nucleotide polymorphisms (SNPs) associated with PCa showing statistical significance of p < 5.0 × 10-5. Seven variants were located at 8q24.21 (rs1016343, rs16901979, and rs13252298 in PRNCR1; rs4242384, rs7837688, and rs1447295 in CASC8; and rs1512268 in NKX3). Two variants located within HNF1B (rs7501939 and rs4430796) had a significant negative association with PCa risk [odds ratio (OR) = 0.717 and 0.747, p = 6.42 × 10-7 and 3.67 × 10-6, respectively]. Of the six independent SNPs that remained after linkage disequilibrium (LD) pruning, the top four SNPs best predicted PCa risk with an area under the receiver operating characteristic curve (AUC) of 0.637 (95% CI: 0.582-0.692). Those with top 25% polygenic risk had a 4.2-fold increased risk of developing PCa compared with those with low risk. CONCLUSION: Eleven PCa risk variants in Korean men were identified; PRSs of a subset of these variants could help predict PCa susceptibility.