Polygenic Risk Score Modifies Prostate Cancer Risk of Pathogenic Variants in Men of African Ancestry.

Unlabelled: Prostate cancer risk is influenced by rare and common germline variants. We examined the aggregate association of rare germline pathogenic/likely pathogenic/deleterious (P/LP/D) variants in ATM, BRCA2, PALB2, and NBN with a polygenic risk score (PRS) on prostate cancer risk among 1,796 prostate cancer cases (222 metastatic) and 1,424 controls of African ancestry. Relative to P/LP/D non-carriers at average genetic risk (33%-66% of PRS), men with low (0%-33%) and high (66%-100%) PRS had Odds Ratios (ORs) for overall prostate cancer of 2.

Association of HCG Level with Ultrasound Visualization of the Gestational Sac in Early Viable Pregnancies.

Our primary objective is to verify or refute a 2013 study by Connolly et al. which showed that in early pregnancy, a gestational sac was visualized 99% of the time on transvaginal ultrasound when the HCG level reached 3510 mIU/mL. Our secondary objective was to make clinical correlations by assessing the relationship between human chorionic gonadotropin (HCG) level in early pregnancy when a gestational sac is not seen and pregnancy outcomes of live birth, spontaneous abortion, and ectopic pregnancy.

Patient compliance and satisfaction with a new forehead device for positional obstructive sleep apnoea treatment: a post hoc analysis of a randomised controlled trial.

Background: The influence of body position in obstructive sleep apnoea patients is well known. A positional therapy device placed at the forehead has proven to be effective in reducing the severity of positional obstructive sleep apnoea (POSA) symptoms. The aim of the study was to evaluate patients' therapy compliance and satisfaction in the short term and mid-term.

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.

Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry.

Background: Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been made in understanding OFCs, due to advances in sequencing and genotyping technologies.

Evidence of Novel Susceptibility Variants for Prostate Cancer and a Multiancestry Polygenic Risk Score Associated with Aggressive Disease in Men of African Ancestry.

Background: Genetic factors play an important role in prostate cancer (PCa) susceptibility.

Objective: To discover common genetic variants contributing to the risk of PCa in men of African ancestry.

Design, Setting, And Participants: We conducted a meta-analysis of ten genome-wide association studies consisting of 19378 cases and 61620 controls of African ancestry.

Changes in Breast Cancer Risk and Risk Factor Profiles among U.S.-Born and Immigrant Asian American Women Residing in the San Francisco Bay Area.

Background: Breast cancer incidence rates in women of Asian descent have been increasing in the United States and Asia.

Methods: In a case-control study of Asian American women from the San Francisco Bay Area, we assessed associations with birthplace and migration-related characteristics and compared risk factors between Asian American and non-Hispanic White women by birthplace and birth cohort.

Results: Birthplace and migration-related characteristics were associated with breast cancer risk only among women in the younger birth cohort (1951-1984) that comprised 355 cases diagnosed at age ≤55 years and 276 sister and population controls.

Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

Eltrombopag in patients with chronic immune thrombocytopenia in Asia-Pacific, the Middle East, and Turkey: final analysis of CITE.

CITE was a prospective, noninterventional study in adult patients with chronic immune thrombocytopenia treated with eltrombopag under routine clinical care in Asia-Pacific, the Middle East, and Turkey. Data to assess eltrombopag usage, compliance, and outcomes were collected from May 2017 to December 2020. Platelet response was defined as platelet count ≥50 × 103/μL in the absence of rescue medications and splenectomy.

Urinary Biomarkers of Polycyclic Aromatic Hydrocarbons and Timing of Pubertal Development: The California PAH Study.

Background: Polycyclic aromatic hydrocarbons (PAHs) are endocrine-disrupting chemicals. Few studies have evaluated the association between pubertal development in girls and PAH exposures quantified by urinary biomarkers.

Methods: We examined associations of urinary PAH metabolites with pubertal development in 358 girls 6-16 years of age from the San Francisco Bay Area enrolled in a prospective cohort from 2011 to 2013 and followed until 2020.

Polygenic risk scores for prediction of breast cancer risk in women of African ancestry: a cross-ancestry approach.

Polygenic risk scores (PRSs) are useful for predicting breast cancer risk, but the prediction accuracy of existing PRSs in women of African ancestry (AA) remains relatively low. We aim to develop optimal PRSs for the prediction of overall and estrogen receptor (ER) subtype-specific breast cancer risk in AA women. The AA dataset comprised 9235 cases and 10 184 controls from four genome-wide association study (GWAS) consortia and a GWAS study in Ghana.

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.

A Rare Germline HOXB13 Variant Contributes to Risk of Prostate Cancer in Men of African Ancestry.

A rare African ancestry-specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry men, including 11 688 prostate cancer cases. The risk allele was present only in men of West African ancestry, with an allele frequency in men that ranged from 0.

Predictors of urinary polycyclic aromatic hydrocarbon metabolites in girls from the San Francisco Bay Area.

Background: Polycyclic aromatic hydrocarbon (PAH) exposures from tobacco smoke, automobile exhaust, grilled or smoked meat and other sources are widespread and are a public health concern, as many are classified as probable carcinogens and suspected endocrine-disrupting chemicals. PAH exposures can be quantified using urinary biomarkers.

Methods: Seven urinary metabolites of naphthalene, fluorene, phenanthrene, and pyrene were measured in two samples collected from girls aged 6-16 years from the San Francisco Bay Area.

Prospective observational study on Pazopanib in patients treated for advanced or metastatic renal cell carcinoma in countries in Asia Pacific, North Africa, and Middle East regions: PARACHUTE study.

Background: Clinical effectiveness and safety data of pazopanib in patients with advanced or mRCC in real-world setting from Asia Pacific, North Africa, and Middle East countries are lacking.

Methods: PARACHUTE is a phase IV, prospective, non-interventional, observational study. Primary endpoint was the proportion of patients remaining progression free at 12 months.

Cumulative menstrual months and breast cancer risk by hormone receptor status and ethnicity: The Breast Cancer Etiology in Minorities Study.

Reproductive and hormonal factors may influence breast cancer risk via endogenous estrogen exposure. Cumulative menstrual months (CMM) can be used as a surrogate measure of this exposure. Using harmonized data from four population-based breast cancer studies (7284 cases and 7242 controls), we examined ethnicity-specific associations between CMM and breast cancer risk using logistic regression, adjusting for menopausal status and other risk factors.

Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.

Our study describes breast cancer risk loci using a cross-ancestry GWAS approach. We first identify variants that are associated with breast cancer at P < 0.05 from African ancestry GWAS meta-analysis (9241 cases and 10193 controls), then meta-analyze with European ancestry GWAS data (122977 cases and 105974 controls) from the Breast Cancer Association Consortium.

New forehead device in positional obstructive sleep apnoea: a randomised clinical trial.

Rationale: Approximately 60% of the patients with obstructive sleep apnoea suffer from a positional effect, and approximately 25% of these patients present events only in the supine position.

Objective: To validate a new positional vibrating device and evaluate its efficacy in reducing the Apnoea-Hypopnoea Index and the total sleep time in the supine position without disturbing sleep.

Methods: A total of 128 patients were recruited for this multicentre, prospective, parallel, randomised controlled trial and were distributed in three arms (general recommendations, inactive and active device).