SYMPTOM OCCURRENCE AND SEVERITY AND HEALTH-RELATED QUALITY OF LIFE IN PATIENTS WITH BREAST OR GYNECOLOGIC CANCER RECEIVING MATCHED CANCER THERAPY

Background: Scientific advancements in oncology allow routine patient cancer genomic profiling, which may guide the choice of novel therapies to match genomic alterations for the treatment of cancer. Potential differences in cancer therapy-related symptom severity and occurrence as well as health-related quality of life (HRQOL) between patients who receive matched therapy and those who do not have not been previously explored. Purposes: The purpose of this study was to describe the characteristics of patients with breast or gynecologic cancer who were receiving matched therapy or not matched therapy, as well as to describe their cancer therapy-related symptom occurrence and severity, and overall HRQOL. Methods: Existing data from the records of 129 patients receiving care at a cancer center in the upper Midwest were used for this descriptive correlational research study. Descriptive statistics and multiple linear regression analyses were performed to address the study purpose and aims. Results: This study found that patients receiving matched therapy had lower mean therapy-related symptom checklist (TRSC) scores (M = 14.7) than patients receiving not matched therapy (M = 16.1). Compared to prior studies, a higher percentage of patients (29%) added symptoms to the TRSC. TRSC scores for individual symptoms were similar across groups, except pain, which was higher in patients receiving matched therapy, and hair loss, which was higher in patients receiving not matched therapy. Patients receiving matched therapy had higher mean Health-Related Quality of Life – Linear Analogue Self Assessment (HRQOL-LASA) scores (M = 48.1), than patients receiving not matched therapy (M = 45.4). Patients who had prior therapy less than three months prior to the onset of the current therapy had significantly higher TRSC total scores than patients with no prior therapy (B = 6.2, p = 0.045). Patients who had a higher number of prior lines of therapy had significantly higher HRQOL-LASA scores (B = 0.56, p = 0.05). Patients with higher TRSC scores had significantly lower HRQOL-LASA (B = -0.36, p < 0.001). Conclusions: Patients receiving matched therapy did not have worse therapy-related symptoms or HRQOL. Findings provide initial information about the symptom experience and HRQOL for patients receiving matched therapy

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Background Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. Methods We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. Results Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. Conclusions Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.Peer reviewe

Distinct genetic architectures for syndromic and nonsyndromic congenital heart defects identified by exome sequencing.

Congenital heart defects (CHDs) have a neonatal incidence of 0.8-1% (refs. 1,2). Despite abundant examples of monogenic CHD in humans and mice, CHD has a low absolute sibling recurrence risk (∼2.7%), suggesting a considerable role for de novo mutations (DNMs) and/or incomplete penetrance. De novo protein-truncating variants (PTVs) have been shown to be enriched among the 10% of 'syndromic' patients with extra-cardiac manifestations. We exome sequenced 1,891 probands, including both syndromic CHD (S-CHD, n = 610) and nonsyndromic CHD (NS-CHD, n = 1,281). In S-CHD, we confirmed a significant enrichment of de novo PTVs but not inherited PTVs in known CHD-associated genes, consistent with recent findings. Conversely, in NS-CHD we observed significant enrichment of PTVs inherited from unaffected parents in CHD-associated genes. We identified three genome-wide significant S-CHD disorders caused by DNMs in CHD4, CDK13 and PRKD1. Our study finds evidence for distinct genetic architectures underlying the low sibling recurrence risk in S-CHD and NS-CHD