Associations between birth defects and childhood and adolescent germ cell tumors according to sex, histologic subtype, and site.

Background: Studies have reported increased rates of birth defects among children with germ cell tumors (GCTs). However, few studies have evaluated associations by sex, type of defect, or tumor characteristics.

Methods: Birth defect-GCT associations were evaluated among pediatric patients (N = 552) with GCTs enrolled in the Germ Cell Tumor Epidemiology Study and population-based controls (N = 6380) without cancer from the Genetic Overlap Between Anomalies and Cancer in Kids Study.

Genetic susceptibility to cognitive decline following craniospinal irradiation for pediatric central nervous system tumors.

Background: Survivors of pediatric central nervous system (CNS) tumors treated with craniospinal irradiation (CSI) exhibit long-term cognitive difficulties. Goals of this study were to evaluate longitudinal effects of candidate and novel genetic variants on cognitive decline following CSI.

Methods: Intelligence quotient (IQ), working memory (WM), and processing speed (PS) were longitudinally collected from patients treated with CSI (n = 241).

Germline genetic variants and pediatric rhabdomyosarcoma outcomes: a report from the Children's Oncology Group.

Background: Relative to other pediatric cancers, survival for rhabdomyosarcoma (RMS) has not improved in recent decades, suggesting the need to enhance risk stratification. Therefore, we conducted a genome-wide association study for event-free survival (EFS) and overall survival (OS) to identify genetic variants associated with outcomes in individuals with RMS.

Methods: The study included 920 individuals with newly diagnosed RMS who were enrolled in Children's Oncology Group protocols.

Exome-wide assessment of isolated biliary atresia: A report from the National Birth Defects Prevention Study using child-parent trios and a case-control design to identify novel rare variants.

The etiology of biliary atresia (BA) is unknown, but recent studies suggest a role for rare protein-altering variants (PAVs). Exome sequencing data from the National Birth Defects Prevention Study on 54 child-parent trios, one child-mother duo, and 1513 parents of children with other birth defects were analyzed. Most (91%) cases were isolated BA.

Trends in Overall Survival among Patients Treated for Sarcoma at a Large Tertiary Cancer Center between 1986 and 2014.

Sarcomas are relatively rare malignancies accounting for about 1% of all cancer diagnoses. Studies on sarcomas comprising large cohorts covering extended time periods are lacking. Therefore, this study aimed to evaluate the impact of demographic, behavioral, and clinical characteristics on overall survival (OS) among individuals diagnosed with soft tissue sarcoma (STS) or bone sarcoma at the Moffitt Cancer Center between 1986 and 2014.

Differential newborn DNA methylation among individuals with complex congenital heart defects and childhood lymphoma.

Background: There is emerging evidence that children with complex congenital heart defects (CHDs) are at increased risk for childhood lymphoma, but the mechanisms underlying this association are unclear. Thus, we sought to evaluate the role of DNA methylation patterns on "CHD-lymphoma" associations.

Methods: From >3 million live births (1988-2004) in California registry linkages, we obtained newborn dried bloodspots from eight children with CHD-lymphoma through the California BioBank.

An updated assessment of 43,110 patients enrolled in the Childhood Cancer Research Network: A Children's Oncology Group report.

Background: The Childhood Cancer Research Network (CCRN) was established by the Children's Oncology Group (COG) as a resource for epidemiologic studies of childhood cancer. The objective of this study was to evaluate the representativeness of CCRN and identify factors associated with enrollment.

Method: The number of US childhood patients with cancer diagnosed <20 years of age enrolled in CCRN (2008-2015) was compared to expected counts, calculated from Surveillance, Epidemiology, and End Results incidence rates and US Census population estimates.

Evaluation of the Sociodemographic, Behavioral and Clinical Influences on Complete Antiretroviral Therapy Adherence Among HIV-Infected Adults Receiving Medical Care in Houston, Texas.

Introduction: Few studies have estimated complete antiretroviral therapy (ART) adherence following HIV infection since the advent of the new ART guidelines in 2012. This study determined the prevalence and influence of sociodemographic, behavioral, and clinical factors on complete ART adherence among people living with HIV (PLWH) receiving medical care in Houston/Harris County, Texas.

Methods: Data from the Houston Medical Monitoring Project survey collected from 2009 to 2014 among 1073 participants were used in this study.

Cerebrospinal Fluid Metabolomic Profiles Associated With Fatigue During Treatment for Pediatric Acute Lymphoblastic Leukemia.

Context: Cancer-related fatigue (CRF) is one of the most distressing and persistent symptoms reported during pediatric acute lymphoblastic leukemia (ALL) therapy; however, information on the pathways underlying CRF severity is limited.

Objectives: We conducted global metabolomics profiling of cerebrospinal fluid (CSF) samples to provide insight into the underlying mechanisms of CRF.

Methods: Fatigue in pediatric ALL patients (2012-2017) was assessed during postinduction therapy approximately six months after diagnosis.

Altered mechanisms of genital development identified through integration of DNA methylation and genomic measures in hypospadias.

Hypospadias is a common birth defect where the urethral opening forms on the ventral side of the penis. We performed integrative methylomic, genomic, and transcriptomic analyses to characterize sites of DNA methylation that influence genital development. In case-control and case-only epigenome-wide association studies (EWAS) of preputial tissue we identified 25 CpGs associated with hypospadias characteristics and used one-sample two stage least squares Mendelian randomization (2SLS MR) to show a causal relationship for 21 of the CpGs.

Utilization of archived neonatal dried blood spots for genome-wide genotyping.

Introduction: Heel pricks are performed on newborns for diagnostic screenings of various pre-symptomatic metabolic and genetic diseases. Excess blood is spotted on Guthrie cards and archived by many states in biobanks for follow-up diagnoses and public health research. However, storage environment may vary across biobanks and across time within biobanks.

Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.

Importance: Birth defects affect approximately 1 in 33 children. Some birth defects are known to be strongly associated with childhood cancer (eg, trisomy 21 and acute leukemia). However, comprehensive evaluations of childhood cancer risk in those with birth defects have been limited in previous studies by insufficient sample sizes.

The role of genetic variation in DGKK on moderate and severe hypospadias.

Background: Recent genome-wide association studies of hypospadias have implicated the role of genetic variants in or near the diacylglycerol kinase kappa (DGKK) gene. However, these variants are largely identified among samples of mild and moderate hypospadias cases. Therefore, we evaluated previously identified DGKK variants among second- and third-degree hypospadias cases and controls recruited in Arkansas, a state characterized by a high birth prevalence of hypospadias.