Per- and polyfluoroalkyl substance concentrations during pregnancy and at birth and risk of childhood acute lymphoblastic leukemia.

Background: Per- and polyfluoroalkyl substances (PFAS) comprise a class of persistent environmental pollutants with potential carcinogenic effects, but their impact on childhood cancer remains underexplored. A child's exposure to PFAS can occur through various pathways postnatally, including contaminated food, water, and consumer products; and in utero, as PFAS can cross the placenta.

Methods: To investigate the association between early-life PFAS exposure and the risk of childhood acute lymphoblastic leukemia (ALL), we analyzed archived blood samples from children diagnosed with ALL and matched cancer-free controls.

Predictors of LexisNexis residential history availability and registry data concordance for childhood cancer research.

Background: Use of a commercial database to obtain residential history information in environmental epidemiologic studies of cancer can lead to information bias if data availability varies by individual socio-demographic factors or case status. Residential data that is not missing at random and data that is discordant with cancer registry or birth record address data can impact subsequent exposure assessments. In our study of childhood cancers, we aimed to determine if availability of residential history information differs by case status or other potential confounders and if there was agreement with cancer registry and birth records address data.

Pre- and Postnatal Exposures to Residential Pesticides and Survival of Childhood Acute Lymphoblastic Leukemia.

Exposure to pesticides has been associated with an increased risk of developing childhood leukemia. However, the impact of pesticides on childhood leukemia survival has not been examined. We investigated the associations between residential pesticide use during key developmental periods and 5-year survival in children treated for acute lymphoblastic leukemia (ALL).

Exposure to per- and polyfluoroalkyl substances in residential settled dust and risk of childhood acute lymphoblastic leukemia.

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous. Young children are commonly exposed to these chemicals via ingestion of settled dust. Several PFAS have been associated with cancers in adults, yet little is known about the risk in children.

Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) from contaminated water and risk of childhood cancer in California, 2000-2015.

Background: Few studies have investigated associations between per- and polyfluoroalkyl substances (PFAS) and childhood cancers. Detectable levels of PFAS in California water districts were reported in the Third Unregulated Contaminant Monitoring Rule for 2013-2015.

Methods: Geocoded residences at birth were linked to corresponding water district boundaries for 10,220 California-born children (aged 0-15 years) diagnosed with cancers (2000-2015) and 29,974 healthy controls.

Folate Metabolism and Risk of Childhood Acute Lymphoblastic Leukemia: A Genetic Pathway Analysis from the Childhood Cancer and Leukemia International Consortium.

Background: Prenatal folate supplementation has been consistently associated with a reduced risk of childhood acute lymphoblastic leukemia (ALL). Previous germline genetic studies examining the one carbon (folate) metabolism pathway were limited in sample size, scope, and population diversity and led to inconclusive results.

Methods: We evaluated whether ∼2,900 single-nucleotide polymorphisms (SNP) within 46 candidate genes involved in the folate metabolism pathway influence the risk of childhood ALL, using genome-wide data from nine case-control studies in the Childhood Cancer and Leukemia International Consortium (n = 9,058 cases including 4,510 children of European ancestry, 3,018 Latinx, and 1,406 Asians, and 92,364 controls).

Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations.

Background: Canine and human osteosarcoma are similar in clinical presentation and tumor genomics. Giant breed dogs experience elevated osteosarcoma incidence, and taller stature remains a consistent risk factor for human osteosarcoma. Whether evolutionarily conserved genes contribute to both human and canine osteosarcoma predisposition merits evaluation.

Pre- and Postnatal Exposures to Tobacco Smoking and Survival of Childhood Acute Lymphoblastic and Myeloid Leukemias in California, United States.

Background: Tobacco smoke adversely affects the prognosis of adult cancers including myeloid leukemia, but less is known in children.

Methods: We evaluated whether pre- and postnatal exposures to tobacco smoke decrease 5-year survival of 1,235 childhood acute lymphoblastic leukemia (ALL) and 188 childhood acute myeloid leukemia (AML) cases derived from a population-based case-control study in California. Cases were diagnosed between 1995 and 2015 (median follow-up time of 13.

Gene-Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia.

Background: Associations between maternal tobacco exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL) have yielded mixed results. This may be due to biases in self-reported smoking or other differences in individual-level risk factors. We utilized a biological marker of maternal tobacco exposure to evaluate the association between maternal tobacco exposure during pregnancy, genetics, and subsequent childhood ALL risk in two large population-based studies of childhood ALL in California.

Evaluating genomic polygenic risk scores for childhood acute lymphoblastic leukemia in Latinos.

The utility of polygenic risk score (PRS) models has not been comprehensively evaluated for childhood acute lymphoblastic leukemia (ALL), the most common type of cancer in children. Previous PRS models for ALL were based on significant loci observed in genome-wide association studies (GWASs), even though genomic PRS models have been shown to improve prediction performance for a number of complex diseases. In the United States, Latino (LAT) children have the highest risk of ALL, but the transferability of PRS models to LAT children has not been studied.

Evaluating Genomic Polygenic Risk Scores for Childhood Acute Lymphoblastic Leukemia in Latinos.

The utility of polygenic risk score (PRS) models has not been comprehensively evaluated for childhood acute lymphoblastic leukemia (ALL), the most common type of cancer in children. Previous PRS models for ALL were based on significant loci observed in genome-wide association studies (GWAS), even though genomic PRS models have been shown to improve prediction performance for a number of complex diseases. In the United States, Latino (LAT) children have the highest risk of ALL, but the transferability of PRS models to LAT children has not been studied.

Birth characteristics and risk of Ewing sarcoma.

Purpose: The incidence of Ewing sarcoma varies according to race and ethnicity, and genetic susceptibility is known to affect disease risk. Apart from these factors, the etiology of Ewing sarcoma is largely unknown.

Methods: We compared the birth characteristics of a population-based series of 556 Ewing sarcoma cases born in California in 1978-2015 and diagnosed in 1988-2015 with those of 27,800 controls selected from statewide birth records and frequency-matched to cases on the year of birth, using multivariable logistic regression models.

Association between birth characteristics and incidence of pituitary adenoma and craniopharyngioma: a registry-based study in California, 2001-2015.

Purpose: To evaluate the association between birth characteristics, including parental sociodemographic characteristics, and early-onset pituitary adenoma (PA) and craniopharyngioma.

Methods: Leveraging the population-based California Linkage Study of Early-onset Cancers, we identified the birth characteristics of incident cases with PA (n = 1,749) or craniopharyngioma (n = 227) who were born from 1978 to 2015 and diagnosed 1988-2015, as well as controls in a 50:1 ratio matched on birth year. Adjusted odds ratios (OR) and 95% confidence interval (CI) estimates were computed using unconditional multivariable logistic regression.

Outdoor artificial light at night, air pollution, and risk of childhood acute lymphoblastic leukemia in the California Linkage Study of Early-Onset Cancers.

Acute lymphoblastic leukemia (ALL) is the most common type of cancer in children (age 0-14 years); however, the etiology remains incompletely understood. Several environmental exposures have been linked to risk of childhood ALL, including air pollution. Closely related to air pollution and human development is artificial light at night (ALAN), which is believed to disrupt circadian rhythm and impact health.

Birth characteristics and risk of meningioma in a population-based study in California.

Background: We evaluated the potential role of birth characteristics in the etiology of early-onset meningioma.

Methods: Leveraging a population-based linkage of California birth records (from 1978 to 2015) and cancer registry data (from 1988 to 2015), we identified 362 nonmalignant meningioma cases aged 0-37 years and selected 18 100 controls matched on year of birth. Cases and controls were compared with regard to birth characteristics, with adjusted odds ratios (ORs) and 95% confidence intervals (CIs) estimated from unconditional multivariable logistic regression models.

Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia.

Genome-wide association studies have identified a growing number of single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL), yet the functional roles of most SNPs are unclear. Multiple lines of evidence suggest that epigenetic mechanisms may mediate the impact of heritable genetic variation on phenotypes. Here, we investigated whether DNA methylation mediates the effect of genetic risk loci for childhood ALL.

Hispanic Ethnicity Differences in Birth Characteristics, Maternal Birthplace, and Risk of Early-Onset Hodgkin Lymphoma: A Population-Based Case-Control Study.

Background: Hispanic ethnicity differences in the risk of early-onset Hodgkin lymphoma diagnosed at <40 years are understudied. We conducted a population-based case-control study to evaluate associations between birth characteristics and early-onset Hodgkin lymphoma with a focus on potential ethnic differences.

Methods: This study included 1,651 non-Hispanic White and 1,168 Hispanic cases with Hodgkin lymphoma endorsing a range of races diagnosed at the age of 0 to 37 years during 1988-2015 and 140,950 controls without cancer matched on race/ethnicity and year of birth from the California Linkage Study of Early-Onset Cancers.

Proximity to endocrine-disrupting pesticides and risk of testicular germ cell tumors (TGCT) among adolescents: A population-based case-control study in California.

Background: The incidence of testicular germ cell tumors (TGCT) is increasing steadily in the United States, particularly among Latinos. TGCT is thought to be initiated in utero and exposure to endocrine-disrupting chemicals, suspected contributors to TGCT pathogenesis, during this critical developmental period may contribute to the rise.

Objectives: To assess the relationship between fetal exposure to agricultural endocrine-disrupting pesticides (EDPs) and TGCT risk among adolescents in a diverse population in California.

Mode of Delivery, Birth Characteristics, and Early-Onset Non-Hodgkin Lymphoma in a Population-Based Case-Control Study.

Background: The etiology of non-Hodgkin lymphoma (NHL) in children and in adolescents and young adults (AYA) is not well understood.

Methods: We evaluated potential associations between mode of delivery, birth characteristics, and NHL risk in a population-based case-control study, which included 3,064 cases of NHL [490 with Burkitt lymphoma, 981 with diffuse large B-cell lymphoma (DLBCL), and 978 with T-cell NHL) diagnosed at the age of 0 to 37 years in California during 1988 to 2015 and 153,200 controls frequency matched on year of birth. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from an unconditional multivariable logistic regression model that included year of birth and birth characteristics.

Epigenetic Biomarkers of Prenatal Tobacco Smoke Exposure Are Associated with Gene Deletions in Childhood Acute Lymphoblastic Leukemia.

Background: Parental smoking is implicated in the etiology of acute lymphoblastic leukemia (ALL), the most common childhood cancer. We recently reported an association between an epigenetic biomarker of early-life tobacco smoke exposure at the gene and increased frequency of somatic gene deletions among ALL cases.

Methods: Here, we further assess this association using two epigenetic biomarkers for maternal smoking during pregnancy-DNA methylation at CpG cg05575921 and a recently established polyepigenetic smoking score-in an expanded set of 482 B-cell ALL (B-ALL) cases in the California Childhood Leukemia Study with available Illumina 450K or MethylationEPIC array data.

History of Early Childhood Infections and Acute Lymphoblastic Leukemia Risk Among Children in a US Integrated Health-Care System.

Surrogate measures of infectious exposures have been consistently associated with lower childhood acute lymphoblastic leukemia (ALL) risk. However, recent reports have suggested that physician-diagnosed early-life infections increase ALL risk, thereby raising the possibility that stronger responses to infections might promote risk. We examined whether medically diagnosed infections were related to childhood ALL risk in an integrated health-care system in the United States.