Statewide trends and factors associated with genetic testing for hereditary cancer risk in Arkansas 2013-2018.

Background: Early identification of hereditary cancer risk would save lives, but genetic testing (GT) has been inadequate. We assessed i) trends for hereditary breast and ovarian cancer (HBOC), Lynch syndrome, and other GT and ii) factors associated with receipt of GT.

Methods: We used data from the Arkansas All-Payer Claims Database from January 2013 through June 2018 (commercial, Medicaid), December 2017 (state employee), or December 2016 (Medicare) and identified enrollees with ≥1 month of enrollment.

Can Automated Alerts in the Electronic Health Record Encourage Referrals for Genetic Counseling and Testing Among Patients at High Risk for Hereditary Cancer Syndromes?

Purpose: Up to 10% of cancers may be associated with an inherited mutation that increases cancer risk. National guidelines emphasize referral for genetic counseling and testing for patients whose personal and/or family history increases their risk of having a hereditary cancer syndrome.

Methods: To increase appropriate referrals for cancer genetic counseling and testing, we piloted an automated alert known as a Best Practice Advisory (BPA) in the electronic health record, Epic, to notify oncology providers when a patient had a personal and/or family history that merited referral to cancer genetics.

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.

Recurrent gynandroblastoma of the ovary with germline mutation: A case report and review of the literature.

Sex cord-stromal tumors (SCSTs) are ovarian tumors that generally present with an adnexal mass and signs/symptoms of hormone excess. Gynandroblastoma is a rare subtype of SCST with a combination of female and male sex cord differentiation. These tumors typically present in premenopausal women and are diagnosed at early stages with benign clinical courses.

What's in Between the Lines: Assessing the Readability, Understandability, and Actionability in Breast Cancer Survivorship Print Materials.

Educational print materials for young women breast cancer survivors (YBCS) are supplemental tools used in patient teaching. However, the readability of the text coupled with how well YBCS understand or act upon the material are rarely explored. The purpose of this study was to assess the readability, understandability, and actionability of commonly distributed breast cancer survivorship print materials.

A case-only study to identify genetic modifiers of breast cancer risk for BRCA1/BRCA2 mutation carriers.

Breast cancer (BC) risk for BRCA1 and BRCA2 mutation carriers varies by genetic and familial factors. About 50 common variants have been shown to modify BC risk for mutation carriers. All but three, were identified in general population studies.

Characterization of the Cancer Spectrum in Men With Germline BRCA1 and BRCA2 Pathogenic Variants: Results From the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Importance: The limited data on cancer phenotypes in men with germline BRCA1 and BRCA2 pathogenic variants (PVs) have hampered the development of evidence-based recommendations for early cancer detection and risk reduction in this population.

Objective: To compare the cancer spectrum and frequencies between male BRCA1 and BRCA2 PV carriers.

Design, Setting, And Participants: Retrospective cohort study of 6902 men, including 3651 BRCA1 and 3251 BRCA2 PV carriers, older than 18 years recruited from cancer genetics clinics from 1966 to 2017 by 53 study groups in 33 countries worldwide collaborating through the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA).

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.

Phase II study of everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer.

Background: Recurrent ovarian, fallopian tube, and peritoneal cancers have limited potential for cure with traditional therapies. Preliminary results from a phase I study of everolimus and bevacizumab in advanced solid tumors showed it to be a promising combination. The primary objective of this study was to evaluate the 6-month progression-free survival for everolimus and bevacizumab in recurrent ovarian, peritoneal, and fallopian tube cancer.

Association of Genomic Domains in and with Prostate Cancer Risk and Aggressiveness.

Pathogenic sequence variants (PSV) in or () are associated with increased risk and severity of prostate cancer. We evaluated whether PSVs in were associated with risk of overall prostate cancer or high grade (Gleason 8+) prostate cancer using an international sample of 65 and 171 male PSV carriers with prostate cancer, and 3,388 and 2,880 male PSV carriers without prostate cancer. PSVs in the 3' region of (c.

The :p.Arg658* truncating variant is associated with risk of triple-negative breast cancer.

Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes , , , , and are associated with breast cancer risk. , which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes.

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.

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.

Phase I study of intravenous oxaliplatin and intraperitoneal docetaxel in recurrent ovarian cancer.

Introduction: Intraperitoneal (IP) chemotherapy improves survival in ovarian cancer but its use has been limited by toxicity with cisplatin-based regimens. The primary objective of this study was to define the maximum tolerated dose and dose-limiting toxicity of intravenous (IV) oxaliplatin and IP docetaxel in women with recurrent ovarian, fallopian tube or peritoneal cancer. Secondary objectives were response rate, time to progression, symptom interference with quality of life, and pharmacokinetics.

Germline pathogenic variants identified in women with ovarian tumors.

Objective: The recognition of genes implicated in ovarian cancer risk beyond BRCA1, BRCA2, and the Lynch syndrome genes has increased the variety of testing options available to providers and patients. We report the frequency of pathogenic variants identified among individuals with ovarian cancer undergoing clinical genetic testing via a multi-gene hereditary cancer panel.

Methods: Genetic testing of up to 32 genes using a hereditary cancer panel was performed on 4439 ovarian cancer cases, and results were analyzed for frequency of pathogenic variants.

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.

Challenges in recruiting African-American women for a breast cancer genetics study.

Background: African-American women, especially in the southern United States, are underrepresented in cancer genetics research. A study was designed to address this issue by investigating the germline mutation rate in African-American women in Arkansas with a personal and/or family history of breast cancer. Women were tested for these mutations using a large panel of breast cancer susceptibility genes.

Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.

The prevalence and spectrum of germline mutations in BRCA1 and BRCA2 have been reported in single populations, with the majority of reports focused on White in Europe and North America. The Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has assembled data on 18,435 families with BRCA1 mutations and 11,351 families with BRCA2 mutations ascertained from 69 centers in 49 countries on six continents. This study comprehensively describes the characteristics of the 1,650 unique BRCA1 and 1,731 unique BRCA2 deleterious (disease-associated) mutations identified in the CIMBA database.

Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer.

Most common breast cancer susceptibility variants have been identified through genome-wide association studies (GWAS) of predominantly estrogen receptor (ER)-positive disease. We conducted a GWAS using 21,468 ER-negative cases and 100,594 controls combined with 18,908 BRCA1 mutation carriers (9,414 with breast cancer), all of European origin. We identified independent associations at P < 5 × 10 with ten variants at nine new loci.

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.

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.

Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.

Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.