Integrative multi-omics analyses to identify the genetic and functional mechanisms underlying ovarian cancer risk regions.

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10).

Large-scale genome-wide association study of 398,238 women unveils seven novel loci associated with high-grade serous epithelial ovarian cancer risk.

Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).

Methods: We analyzed >22 million variants for 398,238 women.

Lifetime ovulatory years and risk of epithelial ovarian cancer: a multinational pooled analysis.

Background: The role of ovulation in epithelial ovarian cancer (EOC) is supported by the consistent protective effects of parity and oral contraceptive use. Whether these factors protect through anovulation alone remains unclear. We explored the association between lifetime ovulatory years (LOY) and EOC.

Copy Number Variants Are Ovarian Cancer Risk Alleles at Known and Novel Risk Loci.

Background: Known risk alleles for epithelial ovarian cancer (EOC) account for approximately 40% of the heritability for EOC. Copy number variants (CNVs) have not been investigated as EOC risk alleles in a large population cohort.

Methods: Single nucleotide polymorphism array data from 13 071 EOC cases and 17 306 controls of White European ancestry were used to identify CNVs associated with EOC risk using a rare admixture maximum likelihood test for gene burden and a by-probe ratio test.

Web-Based Mindfulness-Based Interventions for Well-being: Randomized Comparative Effectiveness Trial.

Background: Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being.

Objective: The primary aim of this study was to determine whether a standard 8-session web-based mindfulness-based cognitive therapy (MBCT) program, compared with a brief 3-session mindfulness intervention, improved overall participant well-being.

Polygenic risk modeling for prediction of epithelial ovarian cancer risk.

Polygenic risk scores (PRS) for epithelial ovarian cancer (EOC) have the potential to improve risk stratification. Joint estimation of Single Nucleotide Polymorphism (SNP) effects in models could improve predictive performance over standard approaches of PRS construction. Here, we implemented computationally efficient, penalized, logistic regression models (lasso, elastic net, stepwise) to individual level genotype data and a Bayesian framework with continuous shrinkage, "select and shrink for summary statistics" (S4), to summary level data for epithelial non-mucinous ovarian cancer risk prediction.

Utilization of genetic testing: Analysis of 4,499 prior authorization requests for molecular genetic tests at four US regional health plans.

Continuous advances in genetic testing methodologies and an increased understanding of the genetic mechanisms of diseases have fueled genetic testing utilization across health care specialties. To our knowledge, national trends in the ordering of genetic testing have not been studied broadly across clinical indications, testing methodologies, and ordering provider specialties. We performed a retrospective analysis of 4,499 complete prior authorization requests for molecular genetic testing submitted to four regional health plans' commercial lines of business between May 1, 2019 and May 31, 2019.

Utilization, Timing, and Outcomes of BRCA Genetic Testing Among Women With Newly Diagnosed Breast Cancer From a National Commercially Insured Population: The ABOARD Study.

Purpose: To evaluate timing and outcomes of BRCA testing and definitive surgical treatment among patients with newly diagnosed breast cancer.

Methods: Patient-reported (n = 1,381) and deidentified health-plan (n = 2,369) data were analyzed from a consecutive national series of 3,750 women whose healthcare providers ordered BRCA testing between March 2014 and June 2015, within 1 year following breast cancer diagnosis.

Results: Among 1,209 respondents, 54.

Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

Offspring sex and risk of epithelial ovarian cancer: a multinational pooled analysis of 12 case-control studies.

While childbearing protects against risk of epithelial ovarian cancer (EOC), few studies have explored the impact on maternal EOC risk of sex of offspring, which may affect the maternal environment during pregnancy. We performed a pooled analysis among parous participants from 12 case-controls studies comprising 6872 EOC patients and 9101 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable logistic regression for case-control associations and polytomous logistic regression for histotype-specific associations, all adjusted for potential confounders.

Harnessing health plan enrollee data to boost membership in patient-powered research networks.

Background: Patient-powered research networks (PPRNs) have been employing and exploring different methods to engage patients in research activities specific to their conditions. One way to intensify patient engagement is to partner with payer stakeholders. The objective of this study was to evaluate the effectiveness of two common payer-initiated outreach methods (postal mail versus email) for inviting prospective candidates to participate in their initiatives.

Publisher Correction: Shared heritability and functional enrichment across six solid cancers.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Data linkages between patient-powered research networks and health plans: a foundation for collaborative research.

Objective: Patient-powered research networks (PPRNs) are a valuable source of patient-generated information. Diagnosis code-based algorithms developed by PPRNs can be used to query health plans' claims data to identify patients for research opportunities. Our objective was to implement privacy-preserving record linkage processes between PPRN members' and health plan enrollees' data, compare linked and nonlinked members, and measure disease-specific confirmation rates for specific health conditions.

Shared heritability and functional enrichment across six solid cancers.

Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r = 0.

A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci.

History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium.

Comorbidities can affect survival of ovarian cancer patients by influencing treatment efficacy. However, little evidence exists on the association between individual concurrent comorbidities and prognosis in ovarian cancer patients. Among patients diagnosed with invasive ovarian carcinoma who participated in 23 studies included in the Ovarian Cancer Association Consortium, we explored associations between histories of endometriosis; asthma; depression; osteoporosis; and autoimmune, gallbladder, kidney, liver, and neurological diseases and overall and progression-free survival.

The Building Blocks of Interoperability. A Multisite Analysis of Patient Demographic Attributes Available for Matching.

Background: Patient matching is a key barrier to achieving interoperability. Patient demographic elements must be consistently collected over time and region to be valuable elements for patient matching.

Objectives: We sought to determine what patient demographic attributes are collected at multiple institutions in the United States and see how their availability changes over time and across clinical sites.

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.

Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies.

Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer.

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.

A Low-density Antigen Array for Detection of Disease-associated Autoantibodies in Human Plasma.

Background/aim: The ability to easily detect autoantibodies will help in the early diagnosis and treatment of certain diseases. Currently, available methods for autoantibody detection are time-consuming and cumbersome. The present study aimed to evaluate the performance of an easy-to-use antigen array developed for autoantibody detection.