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Background: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. Methods: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). Results: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P <.05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. Conclusion: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZ-adjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs)—including apoptotic bodies, microvesicles, and exosomes—are released by almost all cell types and contain molecular footprints from their cell of origin, including lipids, proteins, metabolites, RNA, and DNA. They have been successfully isolated from blood, urine, semen, and other body fluids. In this review, we discuss the current understanding of the predictive value of EVs in prostate and renal cancer. We also describe the findings supporting the use of EVs from liquid biopsies in stratifying high-risk prostate/kidney cancer and advanced disease, such as castration-resistant (CRPC) and neuroendocrine prostate cancer (NEPC) as well as metastatic renal cell carcinoma (RCC). Assays based on EVs isolated from urine and blood have the potential to serve as highly sensitive diagnostic studies as well as predictive measures of tumor recurrence in patients with prostate and renal cancers. Overall, we discuss the biogenesis, isolation, liquid-biopsy, and therapeutic applications of EVs in CRPC, NEPC, and RCC. [ABSTRACT FROM AUTHOR]

BACKGROUND: The early detection of clinically significant prostate cancer (csPCa) through the integration of multidimensional parameters presents a promising avenue for improving survival outcomes for this fatal disease. This study aimed to assess the contribution of prostate transition zone (TZ) to predictive models based on the prostate health index (PHI), with the goal of enhancing early detection of csPCa in the prostate-specific antigen (PSA) gray zone. METHODS: In this observational cross-sectional study, a total of 177 PSA gray zone patients (total prostate-specific antigen [tPSA] level ranging from 4.0 to 10.0 ng/mL) were recruited and received PHI detections from August 2020 to March 2022. Prostatic morphologies especially the TZ morphological parameters were measured by transrectal ultrasound (TRUS). RESULTS: Univariable logistic regression indicated prostatic morphological parameters including total prostate volume (PV) indexes and transitional zone volume indexes were all associated with csPCa (P < .05), while the multivariable analysis demonstrated that C-reactive protein (CRP), PHI, PHI density (PHID), and PHI transition zone density (PHI-TZD) were the 4 independent risk factors. The receiver-operating characteristic (ROC) curve analysis suggested that integrated predictive models (PHID, PHI-TZD) yield area under the curves (AUCs) of 0.9135 and 0.9105 in csPCa prediction, which shows a relatively satisfactory predictive capability compared with other predictors. Moreover, the PHI-TZD outperformed PHID by avoiding 30 patients' unnecessary biopsies while maintaining 74.36% specificity at a sensitivity of 90%. Decision-curve analysis (DCA) confirmed the comparable performance of the multivariable full-risk prediction models, without the inclusion of the net benefit, thereby highlighting the superior diagnostic efficacy of PHID and PHI-TZD in comparison with other diagnostic models, in both univariable and multivariable models. CONCLUSION: Our data confirmed the value of prostate TZ morphological parameters and suggested a significant advantage for the TZadjusted PHI predictive model (PHI-TZD) compared with PHI and PHID in the early detection of gray zone csPCa under specific conditions. [ABSTRACT FROM AUTHOR]

Background: Early screening of clinically significant prostate cancer (csPCa) may offer opportunities in revolutionizing the survival benefits of this lethal disease. We sought to introduce a modified prostate health index density (mPHI) model using imaging indicators and to compare its diagnostic performance for early detection of occult onset csPCa within the prostate-specific antigen (PSA) gray zone with that of PHI and PHID. Methods and Participation: Between August 2020 and January 2022, a training cohort of 278 patients (total PSA 4.0–10.0 ng/ml) who were scheduled for a prostate biopsy were prospectively recruited. PHI and PHID were compared with mPHI ( LD TRD × APD × TPV × PHI) for the diagnosis performance in identifying csPCa. Pathology outcomes from systematic prostate biopsies were considered the gold standard. Results: This model was tested in a training cohort consisting of 73 csPCa, 14 non-clinically significant prostate cancer(non-csPCa), and 191 benign prostatic hyperplasia (BPH) samples. In the univariate analysis for the PSA gray zone cohort, for overall PCa, the AUC of mPHI (0.856) was higher than PHI (0.774) and PHID (0.835). For csPCa, the AUC of mPHI (0.859) also surpassed PHI (0.787) and PHID (0.825). For detection of csPCa, compared with lower specificities from PHI and PHID, mPHI performed the highest specificity (76.5%), by sparing 60.0% of unnecessary biopsies at the cost of missing 11 cases of csPCa. The mPHI outperformed PHI and PHID for overall PCa detection. In terms of csPCa, mPHI exceeds diagnostic performance with a better net benefit in decision curve analysis (DCA) compared with PHI or PHID. Conclusions: We have developed a modified PHI density (mPHI) model that can sensitively distinguish early-stage csPCa patients within the PSA gray zone. Clinical Trial Registration: ClinicalTrials.gov , NCT04251546. [ABSTRACT FROM AUTHOR]

Objectives: To compare the accuracy of several volume and diameters modified prostate health index (mPHI) models with PHI density (PHID), PHI, and other prostate-specific antigen (PSA) derivatives in detecting PSA grey zone prostate cancer (PCa). Materials and methods: Between August 2020 and September 2021, a consecutive cohort of 214 suspected PCa patients with elevated total PSA values ranged from 4.0 to 10.0 ng/mL were prospectively recruited and received PHI detections and transrectal ultrasonography (TRUS) measurements, followed by systematic prostate biopsies confirmation. Results: Among the 214 patients enrolled in the project, a total of 80 were diagnosed with PCa. In univariate analysis for the training cohort, the area under curve (AUC) of mPHI-2 LD TRD × APD × TPV × PHI was 0.8310, which outperformed PHID in identifying PSA grey zone PCa (P ≤ 0.0001) and showed the best net benefit in decision curve analysis (DCA). By a threshold of 0.2835, the sensitivity and specificity in the prediction of PCa were 78.9% and 90.3%, while the positive predictive value (PPV) and negative predictive value (NPV) were 78.3% and 78.6%, respectively. Conclusions: According to our present single-center experience, the mPHI-2 risk predictor outperformed PHID or other classical parameters alone in the PCa detection with a grey zone PSA level in Asian males. [ABSTRACT FROM AUTHOR]

Some tumours may not be detected by ultrasound during biopsy, but recent evidence has shown that different tissues can be discerned by electric impedance. This paper explores the application of vibrotactile feedback in an electrode embedded needle to help classify tissue during fine-needle aspiration biopsy from bioimpedance measurements. The process uses electric impedance spectroscopy from 10 Hz to 349 kHz to fit the double-dispersion Cole model through the Newton-Raphson algorithm. A Naive Bayes classifier is then used on the equivalent circuit parameters to estimate the tissue at the needle tip. The method is validated through a series of experiments and user trials. The results show that the vibrotactile feedback is able to help the operator in determining the tissue the needle is in, suggesting that this may prove to be a useful supplement to the standard procedure used today. [ABSTRACT FROM AUTHOR]

Background The hereditary predisposition to diabetes is only partially explained by genes identified so far. Neurofibromatosis type 1 (NF1) is a rare monogenic dominant syndrome caused by aberrations of the NF1 gene. Here, we used a cohort of 1410 patients with NF1 to study the association of the NF1 gene with type 1 (T1D) and type 2 diabetes (T2D). Methods A total of 1410 patients were confirmed to fulfil the National Institutes of Health diagnostic criteria for NF1 by individually reviewing their medical records. The patients with NF1 were compared with 14 017 controls matched for age, sex and area of residence as well as 1881 non-NF1 siblings of the patients with NF1. Register-based information on purchases of antidiabetic medication and hospital encounters related to diabetes were retrieved. The Cox proportional hazards model was used to calculate the relative risk for diabetes in NF1. Results Patients with NF1 showed a lower rate of T2D when compared with a 10-fold control cohort (HR 0.27, 95% CI 0.17 to 0.43) or with their siblings without NF1 (HR 0.28, 95% CI 0.16 to 0.47). The estimates remained practically unchanged after adjusting the analyses for history of obesity and dyslipidaemias. The rate of T1D in NF1 was decreased although statistically non-significantly (HR 0.58, 95% CI 0.27 to 1.25). Conclusion Haploinsufficiency of the NF1 gene may protect against T2D and probably T1D. Since NF1 negatively regulates the Ras signalling pathway, the results suggest that the Ras pathway may be involved in the pathogenesis of diabetes. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is a common, serious form of cancer in men that is still prevalent despite ongoing developments in diagnostic oncology. Current detection methods lead to high rates of inaccurate diagnosis. We present a method to directly model and exploit temporal aspects of temporal enhanced ultrasound (TeUS) for tissue characterization, which improves malignancy prediction. We employ a probabilistic-temporal framework, namely, hidden Markov models (HMMs), for modeling TeUS data obtained from PCa patients. We distinguish malignant from benign tissue by comparing the respective log-likelihood estimates generated by the HMMs. We analyze 1100 TeUS signals acquired from 12 patients. Our results show improved malignancy identification compared to previous results, demonstrating over 85% accuracy and AUC of 0.95. Incorporating temporal information directly into the models leads to improved tissue differentiation in PCa. We expect our method to generalize and be applied to other types of cancer in which temporal-ultrasound can be recorded. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is one of the most common cancers worldwide and a leading cause of cancer-related mortality. Although the diagnosis and treatment of prostate cancer has improved substantially in recent years, new molecular biomarkers are needed to further prolong survival and improve the quality of life in these patients. This review analyzes the current evidence for prognostic and predictive molecular biomarkers that can be applied across different clinical scenarios, ranging from localized disease to metastatic castration-resistant PCa, with a particular emphasis on the biomarkers likely to become available in routine clinical practice in the near future. There is a growing need for molecular testing to identify the most indolent types of prostate cancer to help optimize treatment strategies and spare treatment in these patients when possible. Current trends in the treatment of prostate cancer underscore the unmet clinical need for biomarkers to improve decision-making in a challenging clinical setting. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate if computer-aided diagnosis (CAD) prior to prostate multi-parametric MRI (mpMRI) can improve sensitivity and agreement between radiologists.Methods: Nine radiologists (three each high, intermediate, low experience) from eight institutions participated. A total of 163 patients with 3-T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS-guided biopsy. Readers were blinded to all outcomes and detected lesions per PI-RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect lesions. Prostatectomy specimens registered to MRI were ground truth with index lesions defined on pathology. Sensitivity, specificity and agreement were calculated per patient, lesion level and zone-peripheral (PZ) and transition (TZ).Results: Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for CAD-assisted mpMRI (p = 0.013). Sensitivity was comparable for TZ lesions (78.7% vs 78.1%; p = 0.929); CAD improved PZ lesion sensitivity (84% vs 94%; p = 0.003). Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion sensitivity was comparable at PI-RADS ≥ 3 (77.6% vs 78.1%; p = 0.859). Per patient specificity was 57.1% for CAD and 70.4% for mpMRI (p = 0.003). CAD improved agreement between all readers (56.9% vs 71.8%; p < 0.001).Conclusions: CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity, between radiologists of varying experience.Key Points: • Computer-aided diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI. • CAD assistance improves agreement between radiologists in detecting prostate cancer lesions. • However, this CAD system induces more false positives, particularly for less-experienced clinicians and in the transition zone. • CAD assists radiologists in detecting cancer missed on MRI, suggesting a path for improved diagnostic confidence. [ABSTRACT FROM AUTHOR]

Purpose: To analyze clinical results and quality of life of patients with localized prostate cancer after irradiation of the prostate with an 18F-choline-PET/CT-based simultaneous integrated boost (SIB) in comparison to a control group without SIB.Methods: A total of 134 patients underwent intensity-modulated radiotherapy from 2007-2010. All patients received a total dose of 76 Gy with 2 Gy fractions to the prostate; 67 patients received an additional SIB of 80 Gy. The median follow-up was 65 months. Quality of life was evaluated with the EPIC (Expanded Prostate Cancer Index Composite) questionnaire.Results: Baseline characteristics were similar in both groups (prostate-specific antigen 11 ng/ml vs. 8 ng/ml, p = 0.20, Gleason score <6 in 36% vs. 46%, p = 0.22, with vs. without SIB). No prostate cancer-related death was observed. No significant difference of quality of life scores was found. The largest difference after 5-6 years in comparison to baseline was reported for sexual bother (mean 15 vs. 17 points with vs. without SIB). Mean urinary scores did not decrease. Bowel bother scores changes were larger in the SIB group (mean 5 vs. 2 points, dependent on SIB volume), with increased bowel problems (15 vs. 2% big/moderate problem with bowel movements, p = 0.03). However, a trend towards higher efficacy with SIB resulted (biochemical recurrence-free survival of 92% vs. 85%, p = 0.17).Conclusions: The first long-term analysis of patients treated with SIB based on molecular imaging with 18-F-choline-PET/CT showed an excellent biochemical recurrence-free survival, but a larger percentage of bowel problems in comparison to the control group. [ABSTRACT FROM AUTHOR]

Previous genome-wide association studies (GWAS) of prostate cancer risk focused on cases unselected for family history and have reported over 100 significant associations. The International Consortium for Prostate Cancer Genetics (ICPCG) has now performed a GWAS of 2511 (unrelated) familial prostate cancer cases and 1382 unaffected controls from 12 member sites. All samples were genotyped on the Illumina 5M+exome single nucleotide polymorphism (SNP) platform. The GWAS identified a significant evidence for association for SNPs in six regions previously associated with prostate cancer in population-based cohorts, including 3q26.2, 6q25.3, 8q24.21, 10q11.23, 11q13.3, and 17q12. Of note, SNP rs138042437 ( p = 1.7e) at 8q24.21 achieved a large estimated effect size in this cohort (odds ratio = 13.3). 116 previously sampled affected relatives of 62 risk-allele carriers from the GWAS cohort were genotyped for this SNP, identifying 78 additional affected carriers in 62 pedigrees. A test for an excess number of affected carriers among relatives exhibited strong evidence for co-segregation of the variant with disease ( p = 8.5e). The majority (92 %) of risk-allele carriers at rs138042437 had a consistent estimated haplotype spanning approximately 100 kb of 8q24.21 that contained the minor alleles of three rare SNPs (dosage minor allele frequencies <1.7 %), rs183373024 (PRNCR1), previously associated SNP rs188140481, and rs138042437 (CASC19). Strong evidence for co-segregation of a SNP on the haplotype further characterizes the haplotype as a prostate cancer predisposition locus. [ABSTRACT FROM AUTHOR]

Objective To evaluate whether biopsy cores taken via a transrectal approach from the anterior apical region of the prostate in a repeat-biopsy population can result in an increased overall cancer detection rate and in more accurate assessment of the Gleason score. Patients and Methods The study was a prospective, randomised (end-fire vs side-fire ultrasound probe) evaluation of 288 men by repeat transrectal saturation biopsy with 28 cores taken from the transition zone, base, mid-lobar, anterior and the anterior apical region located ventro-laterally to the urethra of the peripheral zone. Results The overall prostate cancer detection rate was 44.4%. Improvement of the overall detection rate by 7.8% could be achieved with additional biopsies of the anterior apical region. Two tumours featuring a Gleason score 7 could only be detected in the anterior apical region. In three cases (2.34%) Gleason score upgrading was achieved by separate analysis of each positive core of the anterior apical region. A five-fold higher cancer detection rate in the anterior apical region compared with the transition zone could be shown. Conclusion Sampling of the anterior apical region results in higher overall cancer detection rate in repeat transrectal saturation biopsies of the prostate. Specimens from this region can detect clinically significant cancer, improve accuracy of the Gleason Scoring and therefore may alter therapy. [ABSTRACT FROM AUTHOR]

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69-0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68-0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58-0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54-0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (<4.0 ng/mL) in both European and African-American men. Our results provide further support that a PC-risk SNP rs2735839 near the KLK3 gene on chromosome 19q13 may be associated with aggressive and high-grade PC. Future prospectively designed, case-case GWAS are needed to identify additional SNPs associated with PC aggressiveness. [ABSTRACT FROM AUTHOR]

Renal cysts are clinically and genetically heterogeneous conditions. Polycystic kidney disease (PKD) is common and its characterization has paved the way for the identification of a growing number of cilia-related disorders (ciliopathies) of which most show cystic kidneys. While the recessive form of PKD (ARPKD) virtually always presents in childhood, early onset can, in some instances, also occur in the dominant form (ADPKD). Both ADPKD genes ( PKD1 and PKD2) can also be inherited in a recessive way, making the story more complex with evidence for a dosage-sensitive network. Several phenocopies are known, and mutations in HNF1ß or genes that typically cause other ciliopathies, such as nephronophthisis, Bardet-Biedl, Joubert syndrome and related disorders, can mimic PKD. An accurate genetic diagnosis is crucial for genetic counseling, prenatal diagnostics, and the clinical management of patients and their families. The increasing number of genes that have to be considered in patients with cystic kidney disease is challenging to address by conventional techniques and largely benefits from next-generation sequencing-based approaches. The parallel analysis of targeted genes considerably increases the detection rate, allows for better interpretation of identified variants, and avoids genetic misdiagnoses. [ABSTRACT FROM AUTHOR]

Prostate cancer is one of the most common malignant tumors and a leading cause of cancer-related morbidity and mortality. Irrespective of the method that allows for risk stratification of prostate cancer suspects, diagnosis relies on tissue sampling through prostate biopsy and subsequent histopathological evaluation. This provides critical information about disease aggressiveness, which is required for adequate patient management. Prostate biopsy methods have significantly evolved over the years, including the definition of indications, sampling schemes and use of imaging techniques (ultrasound and MRI) that allow for more accurate tissue sampling. In response to the challenges emerging from more precise collection of minute prostate tissue samples for analysis, histopathological assessment should include not only the observation of routinely stained sections, but also, and increasingly so, a series of ancillary techniques, especially immunohistochemistry, which increment the accuracy of prostate cancer diagnosis and may provide relevant information to guide patient management. [ABSTRACT FROM AUTHOR]

Genetic variation at 8q24 is associated with prostate, bladder, breast, colorectal, thyroid, lung, ovarian, UADT, liver and stomach cancers. However, a role for variation at 8q24 in familial clustering of upper gastrointestinal cancers has not been studied. In order to explore potential inherited susceptibility, we analyzed epidemiologic data from a population-based case-control study of upper gastrointestinal cancers from Taixing, China. The study population includes 204 liver, 206 stomach, and 218 esophageal cancer cases and 415 controls. Associations between 8q24 rs1447295, rs16901979, rs6983267 and these cancers were stratified by family history of cancer. Odds ratios and 95 % confidence intervals were adjusted for potential confounders: age, sex, education, tobacco smoking, alcohol consumption, and BMI at interview. We also adjusted for hepatitis B and aflatoxin (liver cancer) and Helicobacter pylori (stomach cancer). In a dominant model, among those with a family history of cancer, rs1447295 was positively associated with liver cancer (OR 2.80; 95 % CI 1.15-6.80). Heterogeneity was observed ( P = 0.029) with rs6983267 and liver cancer, with positive association in the dominant model among those with a family history of cancer and positive association in the recessive model among those without a family history of cancer. When considered in a genetic risk score model, each additional 8q24 risk genotype increased the odds of liver cancer by two-fold among those with a family history of cancer (OR 2.00; 95 % CI 1.15-3.47). These findings suggest that inherited susceptibility to liver cancer may exist in the Taixing population and that variation at 8q24 might be a genetic component of that inherited susceptibility. [ABSTRACT FROM AUTHOR]

Previous GWAS studies have reported significant associations between various common SNPs and prostate cancer risk using cases unselected for family history. How these variants influence risk in familial prostate cancer is not well studied. Here, we analyzed 25 previously reported SNPs across 14 loci from prior prostate cancer GWAS. The International Consortium for Prostate Cancer Genetics (ICPCG) previously validated some of these using a family-based association method (FBAT). However, this approach suffered reduced power due to the conditional statistics implemented in FBAT. Here, we use a case-control design with an empirical analysis strategy to analyze the ICPCG resource for association between these 25 SNPs and familial prostate cancer risk. Fourteen sites contributed 12,506 samples (9,560 prostate cancer cases, 3,368 with aggressive disease, and 2,946 controls from 2,283 pedigrees). We performed association analysis with Genie software which accounts for relationships. We analyzed all familial prostate cancer cases and the subset of aggressive cases. For the familial prostate cancer phenotype, 20 of the 25 SNPs were at least nominally associated with prostate cancer and 16 remained significant after multiple testing correction ( p ≤ 1 E) occurring on chromosomal bands 6q25, 7p15, 8q24, 10q11, 11q13, 17q12, 17q24, and Xp11. For aggressive disease, 16 of the SNPs had at least nominal evidence and 8 were statistically significant including 2p15. The results indicate that the majority of common, low-risk alleles identified in GWAS studies for all prostate cancer also contribute risk for familial prostate cancer, and that some may contribute risk to aggressive disease. [ABSTRACT FROM AUTHOR]

Despite the family aggregation of severe teenage acne, the genetic basis of this common skin condition remains unclear. We conducted a genome-wide association study (GWAS) on severe teenage acne in 928 European Americans. The SNP rs4133274 on chromosome 8q24 (72 kb upstream of MYC) revealed the most significant association with severe teenage acne ( p value = 1.7 × 10). The variant allele of this SNP (G allele) was associated with an increased risk of severe teenage acne with odds ratio of 4.01 (95 % confidence interval = 2.37-6.82). Upon further replication, our findings suggest new genetic basis of acne and may explain the association between acne and cancer risk observed in the epidemiological studies. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? There is now clear evidence that prostate-specific antigen testing will reduce death from prostate cancer and this data can be used to define those subgroups of men that most stand to benefit from prostate cancer screening. This will help minimise over-detection and improve information provided, so men can provide informed consent. We feel that risk-adjusted screening guidelines, such as the one proposed in the present article, should become the new standard for prostate cancer testing, which will hopefully resolve some of the confusion held by patients and clinicians alike. Currently there is significant confusion and polarisation about prostate cancer screening for both patients and physicians alike., We propose a risk-adjusted testing programme, which would lead to fewer patients who need to be tested and treated to save a life and also eliminate inappropriate prostate-specific antigen testing in the elderly and patients with severe co-morbidities where there is no clear benefit. [ABSTRACT FROM AUTHOR]

Disease risk-associated single nucleotide polymorphisms (SNPs) identified from genome-wide association studies (GWAS) have the potential to be used for disease risk prediction. An important feature of these risk-associated SNPs is their weak individual effect but stronger cumulative effect on disease risk. To date, a stable summary estimate of the joint effect of genetic variants on disease risk prediction is not available. In this study, we propose to use the graded response model (GRM), which is based on the item response theory, for estimating the individual risk that is associated with a set of SNPs. We compare the GRM with a recently proposed risk prediction model called cumulative relative risk (CRR). Thirty-three prostate cancer risk-associated SNPs were originally discovered in GWAS by December 2009. These SNPs were used to evaluate the performance of GRM and CRR for predicting prostate cancer risk in three GWAS populations, including populations from Sweden, Johns Hopkins Hospital, and the National Cancer Institute Cancer Genetic Markers of Susceptibility study. Computational results show that the risk prediction estimates of GRM, compared to CRR, are less biased and more stable. [ABSTRACT FROM AUTHOR]

Approximately 40 single nucleotide polymorphisms (SNPs) that are associated with prostate cancer (PCa) risk have been identified through genome-wide association studies (GWAS). However, these GWAS-identified PCa risk-associated SNPs can explain only a small proportion of heritability (~13%) of PCa risk. Gene-gene interaction is speculated to be one of the major factors contributing to the so-called missing heritability. To evaluate the gene-gene interaction and PCa risk, we performed a two-stage genome-wide gene-gene interaction scan using a novel statistical approach named 'Boolean Operation-based Screening and Testing'. In the first stage, we exhaustively evaluated all pairs of SNP-SNP interactions for ~500,000 SNPs in 1,176 PCa cases and 1,101 control subjects from the National Cancer Institute Cancer Genetic Markers of Susceptibility (CGEMS) study. No SNP-SNP interaction reached a genome-wide significant level of 4.4E−13. The second stage of the study involved evaluation of the top 1,325 pairs of SNP-SNP interactions ( P <1.0E−08) implicated in CGEMS in another GWAS population of 1,964 PCa cases from the Johns Hopkins Hospital (JHH) and 3,172 control subjects from the Illumina iControl database. Sixteen pairs of SNP-SNP interactions were significant in the JHH population at a P cutoff of 0.01. However, none of the 16 pairs of SNP-SNP interactions were significant after adjusting for multiple tests. The current study represents one of the first attempts to explore the high-dimensional etiology of PCa on a genome-wide scale. Our results suggested a list of SNP-SNP interactions that can be followed in other replication studies. [ABSTRACT FROM AUTHOR]

Multiple prostate cancer (PCa) risk-related loci have been discovered by genome-wide association studies (GWAS) based on case-control designs. However, GWAS findings may be confounded by population stratification if cases and controls are inadvertently drawn from different genetic backgrounds. In addition, since these loci were identified in cases with predominantly sporadic disease, little is known about their relationships with hereditary prostate cancer (HPC). The association between seventeen reported PCa susceptibility loci was evaluated with a family-based association test using 1,979 hereditary PCa families of European descent collected by members of the International Consortium for Prostate Cancer Genetics, with a total of 5,730 affected men. The risk alleles for 8 of the 17 loci were significantly over-transmitted from parents to affected offspring, including SNPs residing in 8q24 (regions 1, 2 and 3), 10q11, 11q13, 17q12 (region 1), 17q24 and Xp11. In subgroup analyses, three loci, at 8q24 (regions 1 and 2) plus 17q12, were significantly over-transmitted in hereditary PCa families with five or more affected members, while loci at 3p12, 8q24 (region 2), 11q13, 17q12 (region 1), 17q24 and Xp11 were significantly over-transmitted in HPC families with an average age of diagnosis at 65 years or less. Our results indicate that at least a subset of PCa risk-related loci identified by case-control GWAS are also associated with disease risk in HPC families. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the effects of germline variation at the 8q24 locus on the development of Multiple myeloma (MM). It notes that the findings of the study reveal that the germline variation at the 8q24 locus which is considered as a hotspot of susceptibility in various cancers contributes to the risk of acquiring MM. The 8q24 locus is also involved in the aetiology of malignancies of B cells via a common regulatory mechanism.

Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive. Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed. Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded. Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region. [ABSTRACT FROM AUTHOR]