Subset scanning for multi-trait analysis using GWAS summary statistics.

Motivation: Multi-trait analysis has been shown to have greater statistical power than single-trait analysis. Most of the existing multi-trait analysis methods only work with a limited number of traits and usually prioritize high statistical power over identifying relevant traits, which heavily rely on domain knowledge.

Results: To handle diseases and traits with obscure etiology, we developed TraitScan, a powerful and fast algorithm that identifies potential pleiotropic traits from a moderate or large number of traits (e.

Exposure to persistent organic pollutants in newborn dried blood spots and childhood acute myeloid leukemia.

Acute myeloid leukemia (AML) is a rare malignancy representing 15-20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health.

Perinatal folate levels do not influence tumor latency or multiplicity in a model of NF1 associated plexiform-like neurofibromas.

Objective: In epidemiological and experimental research, high folic acid intake has been demonstrated to accelerate tumor development among populations with genetic and/or molecular susceptibility to cancer. Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder predisposing affected individuals to tumorigenesis, including benign plexiform neurofibromas; however, understanding of factors associated with tumor risk in NF1 patients is limited. Therefore, we investigated whether pregestational folic acid intake modified plexiform-like peripheral nerve sheath tumor risk in a transgenic NF1 murine model.

Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia.

Racial and ethnic and socioeconomic disparities in childhood cancer incidence trends in the United States, 2000-2019.

Background: Population-based surveillance of pediatric cancer incidence trends is critical to determine high-risk populations, drive hypothesis generation, and uncover etiologic heterogeneity. We provide a comprehensive update to the current understanding of pediatric cancer incidence trends by sex, race and ethnicity, and socioeconomic status (SES).

Methods: The Surveillance, Epidemiology, and End Results 22 data (2000-2019) was used to summarize age-adjusted incidence rates for children and adolescents aged 0-19 years at diagnosis.

Children's Oncology Group's 2023 blueprint for research: Epidemiology.

The Children's Oncology Group (COG) Epidemiology Committee has a primary focus on better understanding the etiologies of childhood cancers. Over the past 10 years, the committee has leveraged the Childhood Cancer Research Network, and now more recently Project:EveryChild (PEC), to conduct epidemiologic assessments of various childhood cancers, including osteosarcoma, neuroblastoma, germ cell tumors, Ewing sarcoma, rhabdomyosarcoma, and Langerhans cell histiocytosis. More recent studies have utilized questionnaire data collected as part of PEC to focus on specific characteristics and/or features, including the presence of congenital disorders and the availability of stored cord blood.

Racial disparities in recommendations for surgical resection of primary brain tumours: a registry-based cohort analysis.

Background: Disparities in treatment and outcomes disproportionately affect minority ethnic and racial populations in many surgical fields. Although substantial research in racial disparities has focused on outcomes, little is known about how surgeon recommendations can be influenced by patient race. The aim of this study was to investigate racial and socioeconomic disparities in the surgical management of primary brain tumors.

KMT2A-D pathogenicity, prevalence, and variation according to a population database.

Introduction: The KMT2 family of genes is essential epigenetic regulators promoting gene expression. The gene family contains three subgroups, each with two paralogues: KMT2A and KMT2B; KMT2C and KMT2D; KMT2F and KMT2G. KMT2A-D are among the most frequent somatically altered genes in several different cancer types.

Clinical and demographic predictors of survival for fibrolamellar carcinoma patients-A patient community, registry-based study.

Fibrolamellar hepatocellular carcinoma (FLC) is a rare primary liver cancer that affects primarily adolescents and young adults. It is associated with a poor overall prognosis. There is a need to better define risk factors, but small sample size has limited such studies.

Landscape of germline cancer predisposition mutations testing and management in pediatrics: Implications for research and clinical care.

As germline genetic testing capacities have improved over the last two decades, increasingly more people are newly diagnosed with germline cancer susceptibility mutations. In the wake of this growth, there remain limitations in both testing strategies and translation of these results into morbidity- and mortality-reducing practices, with pediatric populations remaining especially vulnerable. To face the challenges evoked by an expanding diversity of germline cancer mutations, we can draw upon a model cancer-associated genetic condition for which we have developed a breadth of expertise in managing, Trisomy 21.

Genetic ancestry, differential gene expression, and survival in pediatric B-cell acute lymphoblastic leukemia.

Background: Black children have lower incidence yet worse survival than White and Latinx children with B-cell acute lymphoblastic leukemia (B-ALL). It is unclear how reported race/ethnicity (RRE) is associated with death in B-ALL after accounting for differentially expressed genes associated with genetic ancestry.

Methods: Using Phase 1 and 2 NCI TARGET B-ALL cases (N = 273; RRE-Black = 21, RRE-White = 162, RRE-Latinx = 69, RRE-Other = 9, RRE-Unknown = 12), we estimated proportions of African (AFR), European (EUR), and Amerindian (AMR) genetic ancestry.

Germline Mutations as a Cause of Childhood Cancer.

Germline de novo mutations (DNMs) represent one of the important topics that need extensive attention from epidemiologists, geneticists, and other relevant stakeholders. Advances in next-generation sequencing technologies allowed examination of parent-offspring trios to ascertain the frequency of germline DNMs. Many epidemiological risk factors for childhood cancer are indicative of DNMs as a mechanism.

Parental Age and Childhood Lymphoma and Solid Tumor Risk: A Literature Review and Meta-Analysis.

Background: Although advanced parental age has been definitively linked to pediatric acute lymphoblastic leukemia, studies of parental age and pediatric solid tumors have not reached firm conclusions. This analysis aimed to elucidate the relationship between parental age and pediatric solid tumors through meta-analysis of existing studies based in population registries.

Methods: We searched Medline (PubMed) and Embase for registry-based studies of parental age and solid tumors through March 2022.

Infant feeding practices and childhood acute leukemia: Findings from the Childhood Cancer & Leukemia International Consortium.

Increasing evidence suggests that breastfeeding may protect from childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). However, most studies have limited their analyses to any breastfeeding, and only a few data have examined exclusive breastfeeding, or other exposures such as formula milk. We performed pooled analyses and individual participant data metaanalyses of data from 16 studies (N = 17 189 controls; N = 10 782 ALL and N = 1690 AML cases) from the Childhood Leukemia International Consortium (CLIC) to characterize the associations of breastfeeding duration with ALL and AML, as well as exclusive breastfeeding duration and age at introduction to formula with ALL.

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.

The Role of Socioeconomic Status and Race/Ethnicity in Malignant Peripheral Nerve Sheath Tumor Survival: A Surveillance, Epidemiology, and End Results-Based Analysis.

Background: Recent investigations of malignant peripheral nerve sheath tumor (MPNST) survival have reported higher mortality among non-White individuals. However, previous analyses have not examined the impact of socioeconomic status (SES) on these observations. This study aims to characterize factors associated with cause-specific MPNST survival, including information related to census-tract-level SES (CT-SES).

Racial and ethnic disparities in pediatric cancer incidence among children and young adults in the United States by single year of age.

Background: Incidence rates of pediatric cancers in the United States are typically reported in 5-year age groups, obscuring variation by single year of age. Additionally, racial and ethnic variation in incidence is typically presented in broad categories rather than by narrow age ranges.

Methods: The Surveillance, Epidemiology, and End Results (SEER) 18 data (2000-2017) were examined to calculate frequencies and age-adjusted incidence rates among individuals aged birth to 39 years.

Using primary teeth and archived dried spots for exposomic studies in children: Exploring new paths in the environmental epidemiology of pediatric cancer.

It is estimated that 300,000 children 0-14 years of age are diagnosed with cancer worldwide each year. While the absolute risk of cancer in children is low, it is the leading cause of death due to disease in children in high-income countries. In spite of this, the etiologies of pediatric cancer are largely unknown.

The Prenatal Origin of Childhood Leukemia: Potential Applications for Epidemiology and Newborn Screening.

Childhood leukemias are heterogeneous diseases with widely differing incident rates worldwide. As circulating tumors, childhood acute leukemias are uniquely accessible, and their natural history has been described in greater detail than for solid tumors. For several decades, it has been apparent that most cases of childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) initiate .

Incidence of second malignancies in individuals diagnosed with malignant peripheral nerve sheath tumors.

Background: The incidence of malignant peripheral nerve sheath tumors (MPNSTs) is low in the general population, although individuals with Neurofibromatosis Type I (NF1) are particularly susceptible. These tumors generally have a high probability of metastasis. The rate and types of second malignancies (SMNs) after a primary diagnosis of MPNST are not well characterized.

Age-, sex- and disease subtype-related foetal growth differentials in childhood acute myeloid leukaemia risk: A Childhood Leukemia International Consortium analysis.

Aim: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases.

Trends in International Incidence of Pediatric Cancers in Children Under 5 Years of Age: 1988-2012.

Background: Pediatric cancer incidence has been steadily increasing over the last several decades with the largest increases reported in infants. Few evaluations have looked at international pediatric cancer incidence trends in the youngest children. The aim of this analysis was to evaluate trends in cancer incidence in children under 5 years of age, overall and by type, using data from () from 1988 to 2012 (CI5 volumes VII-XI).

Residential mobility in early childhood and the impact on misclassification in pesticide exposures.

Studies of environmental exposures and childhood cancers that rely on records often only use maternal address at birth or address at cancer diagnosis to assess exposures in early childhood, possibly leading to exposure misclassification and questionable validity due to residential mobility during early childhood. Our objective was to assess patterns and identify factors that may predict residential mobility in early childhood, and examine the impact of mobility on early childhood exposure assessment for agriculturally applied pesticides and childhood cancers in California. We obtained the addresses at diagnosis of all childhood cancer cases born in 1998-2011 and diagnosed at 0-5 years of age (n = 6478) from the California Cancer Registry (CCR), and their birth addresses from linked birth certificates.