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The demographic and epidemiological transitions of the past 200 years are well documented at an aggregate level. Understanding differences in individual and group risks for mortality during these transitions requires linkage between demographic data and detailed individual cause of death information. This paper describes the digitization of almost 185,000 causes of death for Ohio to supplement demographic information in the Longitudinal, Intergenerational Family Electronic Micro-database (LIFE-M). To extract causes of death, our methodology combines handwriting recognition, extensive data cleaning algorithms, and the semi-automated classification of causes of death into International Classification of Diseases (ICD) codes. Our procedures are adaptable to other collections of handwritten data, which require both handwriting recognition and semi-automated coding of the information extracted.

Cytomegalovirus (CMV) is among the most common viral infections after solid organ transplantation (SOT). Associations of CMV with cancer risk among SOT recipients have been incompletely evaluated.The authors used linked data from the US SOT registry and 32 cancer registries. Poisson regression was used to compare cancer incidence across CMV risk groups based on donor (D) and recipient (R) immunoglobulin G (IgG) serostatus: high risk (R-negative/D-positive), moderate risk (R-positive), and low risk (R-negative/D-negative).In total, 247,318 SOT recipients were evaluated during 2000-2017 (R-negative/D-positive, 20.3%; R-positive, 62.9%; R-negative/D-negative, 16.8%). CMV-seropositive recipients were older, more racially/ethnically diverse, and had lower socioeconomic status than CMV-seronegative recipients. Compared with R-negative/D-negative recipients, recipients in the R-negative/D-positive and R-positive groups had a lower incidence of diffuse large B-cell lymphoma (DLBCL; R-negative/D-positive: adjusted incidence rate ratio [aIRR], 0.74; 95% confidence interval [CI], 0.59-0.91; R-positive: aIRR, 0.83; 95% CI, 0.69-1.00). CMV serostatus modified the association between Epstein-Barr virus (EBV) status and DLBCL (p = .0006): DLBCL incidence was increased for EBV R-negative/D-positive recipients (aIRR, 3.46; 95% CI, 1.50-7.95) among CMV R-negative/D-negative recipients but not among the other CMV risk groups. Compared with recipients who were CMV R-negative/D-negative, those who were R-negative/D-positive had a lower incidence of small intestine cancer (aIRR, 0.23; 95% CI, 0.09-0.63), and R-positive recipients had a higher incidence of lung cancer (aIRR, 1.24; 95% CI, 1.05-1.46). CMV status was not associated with risk for other cancers.CMV status was not associated with risk for most cancers among SOT recipients. The inverse association with DLBCL may reflect the protective effects of CMV prophylaxis or treatment with off-target efficacy against EBV infection (the major cause of lymphoma in SOT recipients).

Acute lymphoblastic leukemia, a heterogenous malignancy characterized by uncontrolled proliferation of lymphoid progenitors and generally initiated in utero, is the most common pediatric cancer. Although incidence of ALL has been steadily increasing in recent decades, no clear reason for this trend has been identified. Rising concurrently with ALL incidence, increasing maternal obesity rates may be partially contributing to increasing ALL prevelance. Epidemiological studies, including a recent meta-analysis, have found an association between maternal obesity and leukemogenesis in offspring, although mechanisms underlying this association remain unknown. Therefore, the purpose of this review is to propose possible mechanisms connecting maternal obesity to ALL risk in offspring, including changes to fetal/neonatal epigenetics, altered insulin-like growth factor profiles and insulin resistance, modified adipokine production and secretion, changes to immune cell populations, and impacts on birthweight and childhood obesity/adiposity. We describe how each proposed mechanism is biologically plausible due to their connection with maternal obesity, presence in neonatal and/or fetal tissue, observation in pediatric ALL patients at diagnosis, and association with leukemogenesis, A description of ALL and maternal obesity trends, a summary of epidemiological evidence, a discussion of the pathway from intrauterine environment to subsequent malignancy, and propositions for future directions are also presented.

Aim: To explore the validity and strength of evidence on the association between environmental factors and risk of developing childhood (0-14 years) cancer. Methods: An umbrella review was conducted including systematic reviews and meta-analyses of observational epidemiological studies that examined the association of any environmental exposure of either parent or child with any type of childhood cancer. PubMed and Scopus databases were searched until April 2020. Based on predefined criteria, the evidence was graded into strong, highly suggestive, suggestive or weak. Results: 509 meta-analyses explored environmental exposures and risk of developing 10 different types of childhood cancer. Only 2.4% of the associations were considered to have highly suggestive evidence inferred by strongly statistically significant results. These associations were confined to increased risk of overall leukemia, especially acute lymphoblastic leukemia (ALL), in relation to high birthweight, paternal smoking and exposure to pesticides, particularly insecticides. By contrast, maternal multivitamin supplementation during pregnancy (summary odds ratio [OR]: 0.64, 95% confidence intervals [CI]: 0.52, 0.80) and breastfeeding for more than 6 months (summary OR: 0.76, 95%CI: 0.68, 0.84) were supported by highly suggestive evidence for decreased risk of ALL. There was also highly suggestive evidence for increased risk of central nervous system (CNS) tumors, especially astrocytoma, in relation to high birthweight, as well as increased risk of testicular cancer in relation to testicular microlithiasis and isolated cryptorchidism. Conclusions: The present findings provide evidence that exposure to seven maternal/neonatal factors significantly affects the risk of childhood leukemia, CNS tumors and testicular cancer. Further evidence from sufficiently powered studies and large consortia with uniform reporting of analyses is needed to allow firmer conclusions to be drawn.

BACKGROUND The use of dried blood spots (DBS) in biomedical research has been increasing as an objective measure for variables that are typically plagued by self-report, such as smoking status and medication adherence. The development of training materials for the self-collection of DBS that can be delivered through the Web would allow for broader use of this methodology. OBJECTIVE The objective of this study was to evaluate the acceptability and feasibility of the self-collection of DBS using newly developed multimedia training materials that were delivered through the Web. We also aimed to assess the usability of the collected DBS samples. METHODS We recruited participants through Facebook advertising for two distinct studies. The first study evaluated the acceptability of our newly developed DBS training materials, while the second assessed the implementation of this protocol into a larger Web-based study. RESULTS In the first study, participants (N=115) were aged, on average, 26.1 (SD 6.4) years. Training materials were acceptable (113/115, 98.2%, of participants were willing to collect DBS again) and produced usable samples (110/115, 95.7%, collected DBS were usable). In the second study, response rate was 25.0% (41/164), with responders being significantly younger than nonresponders (20.3 [SD 0.2] vs 22.0 [SD 0.4]; P CONCLUSIONS Overall, while the protocol is acceptable, feasible, and produced usable samples, additional work is needed to improve response rates.

Introduction: Children with congenital heart defects (CHD) are a unique population with abbreviated survival compared to the general population. Case-control studies have suggested an elevated risk of childhood cancer in children with CHD. This has not been evaluated in prospective studies nor has risk of cancer in adult survivors of CHD. This study describes mortality from cancer among survivors of CHD in the Pediatric Cardiac Care Consortium (PCCC). Methods: We performed a retrospective cohort study of individuals who underwent surgery for CHD at 0-21 years of age in the PCCC during 1982-2003. Patients surviving their first CHD surgery (n= 35,998) were linked to the National Death Index (NDI) through 2014. Cancer mortality was compared to that in the general population using standardized mortality ratios (SMRs) matched on age, year, and sex. Results: Seventy patients were identified as having an underlying cause of death as cancer and surviving a CHD operation in the PCCC (males, n=38). Of these, 17 (24.3%) had a diagnosis of Trisomy 21. Deaths occurred over a median follow-up of 8.81 years (IQR: 5.9-15.8) post hospital discharge with median age at death of 13.5 years (IQR: 7.0-20.0). Overall adjusted SMRs for deaths relating to cancer were 2.75 (95% CI: 2.11-3.40) and increased for those with a chromosomal abnormality (2.31 to 6.76). Decrease in mortality was observed the older the patient was at CHD surgery (neonate to adolescence: 5.03 to 1.65 respectively). Increased mortality in surgically severe CHDs (SMR: 4.75; 95% CI: 2.26-7.23) was seen. Conclusions: The PCCC-NDI linked database leverages the largest cohort of children with CHD in the U.S. We found an increased risk of death from cancer, especially in those with chromosomal abnormalities. This may demonstrate an increased risk of cancer, but could indicate higher risk of death from cancer for children who previously had CHD. To resolve these possibilities we will link to cancer registries to obtain incident disease. N (%)SMR95% CIOVERALL702.75(2.11-3.40)Lesion GroupLeft-to-Right Lesions36 (51.4)2.82(1.90-3.75)Impaired Systemic Flow13 (18.5)2.71(1.23-4.18)Impaired Pulmonary Flow7 (10.0)2.52(0.65-4.39)Complex Lesions3 (4.3)2.07(0.0-4.42)Anomalous Pulmonary Venous Return2 (2.9)5.92(0.0-14.12)Transposition Physiology2 (2.9)2.74(0.0-6.55)Other4 (5.7)2.38(0.05-4.71)Single Ventricle3 (4.3)3.74(0.0-7.98)Age at SurgeryNeonate12 (17.2)5.03(2.19-7.88)Infant17 (24.3)3.14(1.65-4.63)Child22 (31.4)3.59(2.09-5.10)Adolescent19 (27.1)1.65(0.91-2.40)Chromosomal AbnormalityYes17 (24.3)6.76(3.55-9.97)No53 (75.7)2.31(1.69-2.94)SeverityModerate28 (40.0)2.99(1.88-4.10)Mild22 (31.4)2.21(1.29-3.13)Severe14 (20.0)4.75(2.26-7.23)N/A6 (8.6)1.91(0.38-3.43) Citation Format: Amanda S. Thomas, Logan Spector, Lazaros K. Kochilas. Cancer mortality in children surviving congenital heart surgery: A study from the pediatric cardiac care consortium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3305.

Introduction: Increases in the incidence of both obesity (a risk factor for many adulthood cancers) and acute lymphoblastic leukemia (ALL) in childhood have been observed over the past three decades, thus we sought to identify whether obesity may be an unrecognized risk factor for childhood ALL. Methods: Demographics, anthropometrics and disease characteristics from children and young adults (aged 1-30 years) diagnosed with ALL between 2004-2017 and treated on Children’s Oncology Group (COG) frontline treatment protocols with available pre-treatment anthropometric data (n=4775, AALL17D2) were compared to National Health and Nutrition Examination Survey (NHANES) controls (n=30,107). Individuals were classified as underweight, normal weight, overweight, or obese, per standard CDC age- and sex-based pediatric and adult definitions for body mass index (BMI). Multivariate logistic regressions were performed, adjusting for sex, race/ethnicity, age, socioeconomic status and obesity status, to assess associations between BMI classification and ALL. Additional models were performed stratifying by ALL disease characteristics. Results: ALL patients (72% B-ALL, 28% T-ALL) were more likely to be male (62%), 58% were non-Hispanic white, 9% non-Hispanic black and 24% identified as Hispanic. Among ALL patients, 5% were underweight, 58% normal weight, 17% overweight and 20% obese. Using normal weight as reference, BMI above normal weight classification was associated with ALL diagnosis (overweight, OR=1.10, 95% CI 1.00-1.20, p=0.046; obese, OR=1.15, 95% CI 1.05-1.25, p=0.002), as was underweight (OR=1.74, 95% CI 1.48-2.03, p= Conclusions: This is the first study, to our knowledge, to show that pre-treatment overweight or obesity is associated with ALL, specifically among males and B-cell immunophenotype. Furthermore, ALL CNS involvement was associated with obesity. This study also confirmed the known association between underweight and ALL. Although the associations between BMI status and newly diagnosed ALL may be secondary to detrimental physiologic effects of ALL (i.e. underweight at time of diagnosis), they also suggest a role for inflammation, environmental exposures, or other genetic susceptibility in ALL pathogenesis. Further analyses are needed to elucidate whether other ALL disease characteristics, such as cytogenetics, may be associated with pre-treatment childhood BMI. Citation Format: Taumoha Ghosh, Michaela Richardson, Justin Ryder, Logan Spector, Lucie Turcotte. Obesity as a risk factor for pediatric acute lymphoblastic leukemia: A report from the Children's Oncology Group [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3118.

Genetic syndromes and pediatric cancers are rare, so instances of co-occurrence raise the question of whether the two conditions may be etiologically linked. Clear examples of causal association can be found in the cancer predisposition syndromes. This report contains the results of a systematic literature search using Ovid Medline for co-occurrence of genetic syndromes with 23 types of pediatric cancer. The results reflect known associations as well as many reports of infrequently observed co-occurrences. This compilation may suggest previously overlooked patterns, and the information could be used to identify gene pathways critical in the development of childhood cancers.

BackgroundHepatoblastoma is a malignancy of young children. Low birth weight is associated with significantly increased risk of hepatoblastoma and neonatal medical exposures are hypothesized as contributors. This study represents the largest case-control study of hepatoblastoma to date and aimed to define the role of neonatal exposures in hepatoblastoma risk among low birth weight children.ProcedureIncident hepatoblastoma cases who were born

Dried blood spots (DBS) are collected uniformly from US newborns to test for metabolic and other disorders. Because evidence exists for prenatal origins of some diseases, DBS may provide unique prenatal exposure records. Some states retain residual DBS and permit their use in aetiological studies. The primary study aim was to assess the feasibility of obtaining residual DBS from state newborn screening programmes for paediatric and adolescent cancer patients nationwide with parental/subject consent/assent. Families of leukaemia and lymphoma patients aged ≤21 years diagnosed from 1998 to 2007 at randomly selected Children's Oncology Group institutions across the US were questioned (n = 947). Parents/guardians and patients aged ≥18 years were asked to release DBS to investigators in spring 2009. DBS were then requested from states. Overall, 299 families (32%) released DBS. Consenting/assenting patients were born in 39 US states and 46 DBS were obtained from five states; 124 DBS were unobtainable because patients were born prior to dates of state retention. State policies are rapidly evolving and there is ongoing discussion regarding DBS storage and secondary research uses. Currently, population-based DBS studies can be conducted in a limited number of states; fortunately, many have large populations to provide reasonably sized paediatric subject groups.