A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer.

Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.

Cluster effect for SNP-SNP interaction pairs for predicting complex traits.

Single nucleotide polymorphism (SNP) interactions are the key to improving polygenic risk scores. Previous studies reported several significant SNP-SNP interaction pairs that shared a common SNP to form a cluster, but some identified pairs might be false positives. This study aims to identify factors associated with the cluster effect of false positivity and develop strategies to enhance the accuracy of SNP-SNP interactions.

Early Prostate Cancer Deaths Among Men With Higher vs Lower Genetic Risk.

Importance: Prostate cancer, a leading cause of cancer death among men, urgently requires new prevention strategies, which may involve targeting men with an underlying genetic susceptibility.

Objective: To explore differences in risk of early prostate cancer death among men with higher vs lower genetic risk to inform prevention efforts.

Design, Setting, And Participants: This cohort study used a combined analysis of genotyped men without prostate cancer at inclusion and with lifestyle data in 2 prospective cohort studies in Sweden and the US, the Malmö Diet and Cancer Study (MDCS) and the Health Professionals Follow-Up Study (HPFS), followed up from 1991 to 2019.

Differential levels of circulating RNAs prior to endometrial cancer diagnosis.

Endometrial cancer (EC) is one of the most common female cancers and there is currently no routine screening strategy for early detection. An altered abundance of circulating microRNAs (miRNAs) and other RNA classes have the potential as early cancer biomarkers. We analyzed circulating RNA levels using small RNA sequencing, targeting RNAs in the size range of 17-47 nucleotides, in EC patients with samples collected prior to diagnosis compared to cancer-free controls.

Germline Sequencing Analysis to Inform Clinical Gene Panel Testing for Aggressive Prostate Cancer.

Importance: Germline gene panel testing is recommended for men with advanced prostate cancer (PCa) or a family history of cancer. While evidence is limited for some genes currently included in panel testing, gene panels are also likely to be incomplete and missing genes that influence PCa risk and aggressive disease.

Objective: To identify genes associated with aggressive PCa.

High use of short-acting β-agonists in COPD is associated with an increased risk of exacerbations and mortality.

Background: Short-acting β-agonist (SABA) overuse has been associated with an increased risk of exacerbations in asthma; however, less is known about SABA use in COPD. Our aim was to describe SABA use and investigate potential associations between high SABA use and the risk of future exacerbations and mortality in COPD.

Methods: This observational study identified COPD patients in primary care medical records in Sweden.

Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry.

Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS.

Biochemical activity induced by a germline variation in (PSA) associates with cellular function and clinical outcome in prostate cancer.

Genetic variation at the 19q13.3 locus is linked with prostate cancer susceptibility. The non-synonymous SNP, rs17632542 (c.

Short-acting β -agonist use and asthma exacerbations in Swedish children: A SABINA Junior study.

Background: In adults and adolescents with asthma, use of ≥3 short-acting β -agonist (SABA) canisters/year is associated with increased exacerbation risk. Whether this association is present in younger children remains unknown. In this SABA use IN Asthma (SABINA) Junior study, we assessed the association of SABA collection with exacerbation risk in the general Swedish pediatric asthma population.

Long-term treatment patterns and survival in metastatic breast cancer by intrinsic subtypes - an observational cohort study in Sweden.

Background: Longitudinal, real-world data on the management of metastatic breast cancer is increasingly relevant to understand breast cancer care in routine clinical practice. Yet such data are scarce, particularly beyond second- and third-line treatment strategies. This study, therefore, examined both the long-term treatment patterns and overall survival (OS) in a regional Swedish cohort of female patients with metastatic breast cancer stratified by subtype in routine clinical practice during a recent eight-year period and correlation to current treatment guidelines.

Family History of Prostate and Breast Cancer Integrated with a Polygenic Risk Score Identifies Men at Highest Risk of Dying from Prostate Cancer before Age 75 Years.

Purpose: Family history of prostate cancer is one of the few universally accepted risk factors for prostate cancer. How much an assessment of inherited polygenic risk for prostate cancer adds to lifetime risk stratification beyond family history is unknown.

Experimental Design: We followed 10,120 men in the Health Professionals Follow-up Study with existing genotype data for risk of prostate cancer and prostate cancer-specific death.

Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men.

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.

Lack of COPD-Related Follow-Up Visits and Pharmacological Treatment in Swedish Primary and Secondary Care.

Objective: The Swedish guidelines recommend that patients with chronic obstructive pulmonary disease (COPD) on maintenance treatment are monitored annually, and within six weeks after an exacerbation. We describe the patterns of COPD-related visits in Sweden, both regular follow-up and post-exacerbation visits.

Methods: Patients (>40 years) with a first-time COPD diagnosis between 2006 and 2017 were identified in primary care medical records and linked to hospital contacts and administered drug data.

Association Study between Polymorphisms in DNA Methylation-Related Genes and Testicular Germ Cell Tumor Risk.

Background: Testicular germ cell tumors (TGCT), histologically classified as seminomas and nonseminomas, are believed to arise from primordial gonocytes, with the maturation process blocked when they are subjected to DNA methylation reprogramming. SNPs in DNA methylation machinery and folate-dependent one-carbon metabolism genes have been postulated to influence the proper establishment of DNA methylation.

Methods: In this pathway-focused investigation, we evaluated the association between 273 selected tag SNPs from 28 DNA methylation-related genes and TGCT risk.

A Healthy Lifestyle in Men at Increased Genetic Risk for Prostate Cancer.

Background: Prostate cancer is the most heritable cancer. There is a need to identify possible modifiable factors for men at an increased risk of prostate cancer due to genetic factors.

Objective: To examine whether men at an increased genetic risk of prostate cancer can offset their risk of disease or disease progression by adhering to a healthy lifestyle.

Annual and Post-Exacerbation Follow-Up of Asthma Patients in Clinical Practice - A Large Population-Based Study in Sweden.

Background: Symptom control has not improved in Swedish asthma patients during the last two decades. Guidelines recommend annual reviews for asthma patients treated with maintenance inhaled corticosteroids (ICS). We aimed to describe how visit patterns in an ICS-treated asthma population in Sweden were related to applicable asthma guidelines.

Prostate cancer risk stratification improvement across multiple ancestries with new polygenic hazard score.

Background: Prostate cancer risk stratification using single-nucleotide polymorphisms (SNPs) demonstrates considerable promise in men of European, Asian, and African genetic ancestries, but there is still need for increased accuracy. We evaluated whether including additional SNPs in a prostate cancer polygenic hazard score (PHS) would improve associations with clinically significant prostate cancer in multi-ancestry datasets.

Methods: In total, 299 SNPs previously associated with prostate cancer were evaluated for inclusion in a new PHS, using a LASSO-regularized Cox proportional hazards model in a training dataset of 72,181 men from the PRACTICAL Consortium.

Identification and Validation of Leucine-rich α-2-glycoprotein 1 as a Noninvasive Biomarker for Improved Precision in Prostate Cancer Risk Stratification.

Background: More accurate risk assessments are needed to improve prostate cancer management.

Objective: To identify blood-based protein biomarkers that provided prognostic information for risk stratification.

Design Setting And Participants: Mass spectrometry was used to identify biomarker candidates from blood, and validation studies were performed in four independent cohorts retrospectively collected between 1988 and 2015.

Identification of 22 susceptibility loci associated with testicular germ cell tumors.

Testicular germ cell tumors (TGCT) are the most common tumor in young white men and have a high heritability. In this study, the international Testicular Cancer Consortium assemble 10,156 and 179,683 men with and without TGCT, respectively, for a genome-wide association study. This meta-analysis identifies 22 TGCT susceptibility loci, bringing the total to 78, which account for 44% of disease heritability.

KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness.

Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP-SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium.