The impact of epidemic infectious diseases on the relationship between subjective well-being and social class identity in older adults: The mediating role of Self-rated health.

BACKGROUND: The purpose of this paper is to explore the relationship between subjective well-being, social class identity, and Self-rated health among older persons,. Focusing on the mediating role of health and the impact of epidemic infectious diseases on these relationships. METHODS: Based on the 2018 and 2021 China General Social Survey (CGSS) databases, the data were screened, and processed. Using Stata17, we employed ordered probit regression to examine the relationships among variables and Bootstrap methods to assess mediation effects, and the CGSS data for 2018 and 2021 were compared and analyzed. RESULTS: Our results revealed that factors such as social class identity, health status, and personal income significantly positively impact older persons' subjective well-being (P<0.01). Notably, there was a partial mediating effect of health status between the subjective well-being of the elderly and social class identity. And findings showed that when older adults were affected by epidemic diseases, their subjective well-being, social class identity, and Self-rated health remained significantly positively correlated. Subjective well-being, social class identity. What is more noteworthy is that when affected by epidemic infectious diseases, older adults' subjective well-being, social class identity, and Self-rated health remained significantly positively correlated. The mediating role of self-rated health in older adults' subjective well-being and social class identity increased from 9.6% to 12.4%. CONCLUSIONS: In the face of epidemic infectious diseases, we need to pay more attention to the Self-rated health of the elderly, and the Chinese government should take effective measures to improve their health level, which will in turn improve the subjective well-being of the elderly and realize the goal of healthy aging.

Evaluation of the genetic basis of familial-associated early-onset hematologic cancers in an ancestral/ethnically diverse population.

Genetic predisposition to hematologic malignancies has historically been addressed utilizing patients recruited from clinical trials and pedigrees constructed at major treatment centers. Such efforts leave unexplored the genetic basis of variations in risk by race/ethnic group shown in population-based surveillance data where cancer registration, compulsory by law, delivers universal enrollment. To address this, we performed exome sequencing on DNA isolated from newborn bloodspots derived from sibling pairs with early-onset cancers across California in which at least one of the siblings developed a hematologic cancer, using unbiased recruitment from the full state population. We identified pathogenic/likely pathogenic (P/ LP) variants among 1,172 selected cancer genes that were private or present at low allele frequencies in reference populations. Within 64 subjects from 32 families, we found 9 LP variants shared between siblings, and an additional 7 such variants in singleton children (not shared with their sibling). In 8 of the shared cases, the ancestral origin of the local haplotype that carries P/LP variants matched the dominant global ancestry of study participant families. This was the case for Latino sibling pairs on FLG and CBLB, non-Latino White sibling pairs in TP53 and NOD2, and a shared GATA2 variant for a non-Latino Black sibling pair. A new inherited mutation in HABP2 was identified in a sibling pair, one with diffuse large B-cell lymphoma and the other with neuroblastoma. Overall, the profile of P/LP germline variants across ancestral/ethnic groups suggests that rare alleles contributing to hematologic diseases originate within their race/ethnic origin parental populations, demonstrating the value of this discovery process in diverse, population-based registries.

RNF167-mediated ubiquitination of Tollip inhibits TNF-α-triggered NF-κB and MAPK activation.

Toll-interacting protein (Tollip) is a multifunctional regulator in cellular activities. However, whether its functions are subjected to post-translational modifications remains elusive. Here, we identified ubiquitination as a post-translational modification on Tollip. We found that Tollip interacted with ring finger protein 167 (RNF167) through its C-terminal coupling of ubiquitin to ER degradation (CUE) domain, and RNF167 functioned as the potential E3 ligase to attach K33-linked poly-ubiquitin chains to the Lys235 (K235) site of Tollip. Furthermore, we discovered Tollip could inhibit TNF-α-induced nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation, and substitution of Lys235 on Tollip to arginine failed to suppress TNF-α-NF-κB/MAPK (JNK) cascades, revealing the role of Tollip and its ubiquitination in NF-κB/MAPK pathways. Thus, our study reveals the novel biological function of Tollip and RNF167-dependent ubiquitination of Tollip in TNF-α signaling.

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. We also assessed whether Ewing sarcoma clustered within families. RESULTS: Compared to non-Hispanic White subjects, Black (odds ratio [OR] = 0.07, 95% confidence interval [CI] 0.03-0.18), Asian (OR = 0.57, 95% CI 0.41-0.80), and Hispanic (OR = 0.73, 95% CI 0.62-0.88) individuals had a significantly lower risk of Ewing sarcoma. Race and ethnicity differences were more profound for metastatic Ewing sarcoma. Birthweight was also identified as a significant risk factor (OR = 1.09, 95% CI 1.00-1.18 for each 500 g increase in birthweight). A separate family-based cancer clustering analysis did not suggest any strong role for familial predisposition alleles. CONCLUSIONS: This population-based study with minimal selection bias provides support for a role of accelerated fetal growth in the etiology of Ewing sarcoma in addition to more precise estimates of racial and ethnic variations in disease risk. This comparatively large analysis of birth characteristics and Ewing sarcoma in a multiethnic population should stimulate further investigations into genetic and environmental causes.

DNA methylation at birth in monozygotic twins discordant for pediatric acute lymphoblastic leukemia.

Aberrant DNA methylation constitutes a key feature of pediatric acute lymphoblastic leukemia at diagnosis, however its role as a predisposing or early contributor to leukemia development remains unknown. Here, we evaluate DNA methylation at birth in 41 leukemia-discordant monozygotic twin pairs using the Illumina EPIC array on archived neonatal blood spots to identify epigenetic variation associated with development of pediatric acute lymphoblastic leukemia, independent of genetic influence. Through conditional logistic regression we identify 240 significant probes and 10 regions associated with the discordant onset of leukemia. We identify a significant negative coefficient bias, indicating DNA hypomethylation in cases, across the array and enhanced in open sea, shelf/shore, and gene body regions compared to promoter and CpG island regions. Here, we show an association between global DNA hypomethylation and future development of pediatric acute lymphoblastic leukemia across disease-discordant genetically identical twins, implying DNA hypomethylation may contribute more generally to leukemia risk.

Interaction between maternal killer immunoglobulin-like receptors and offspring HLAs and susceptibility of childhood ALL.

Acute lymphoblastic leukemia (ALL) in children is associated with a distinct neonatal cytokine profile. The basis of this neonatal immune phenotype is unknown but potentially related to maternal-fetal immune receptor interactions. We conducted a case-control study of 226 case child-mother pairs and 404 control child-mother pairs to evaluate the role of interaction between HLA genotypes in the offspring and maternal killer immunoglobulin-like receptor (KIR) genotypes in the etiology of childhood ALL, while considering potential mediation by neonatal cytokines and the immune-modulating enzyme arginase-II (ARG-II). We observed different associations between offspring HLA-maternal KIR activating profiles and the risk of ALL in different predicted genetic ancestry groups. For instance, in Latino subjects who experience the highest risk of childhood leukemia, activating profiles were significantly associated with a lower risk of childhood ALL (odds ratio [OR] = 0.59; 95% confidence interval [CI], 0.49-0.71) and a higher level of ARG-II at birth (coefficient = 0.13; 95% CI, 0.04-0.22). HLA-KIR activating profiles were also associated with a lower risk of ALL in non-Latino Asians (OR = 0.63; 95% CI, 0.38-1.01), although they had a lower tumor necrosis factor-α level (coefficient = -0.27; 95% CI, -0.49 to -0.06). Among non-Latino White subjects, no significant association was observed between offspring HLA-maternal KIR interaction and ALL risk or cytokine levels. The current study reports the association between offspring HLA-maternal KIR interaction and the development of childhood ALL with variation by predicted genetic ancestry. We also observed some associations between activating profiles and immune factors related to cytokine control; however, cytokines did not demonstrate causal mediation of the activating profiles on ALL risk.

Increased burden of familial-associated early-onset cancer risk among minority Americans compared to non-Latino Whites.

Background: The role of race/ethnicity in genetic predisposition of early-onset cancers can be estimated by comparing family-based cancer concordance rates among ethnic groups. Methods: We used linked California health registries to evaluate the relative cancer risks for first-degree relatives of patients diagnosed between ages 0 and 26, and the relative risks of developing distinct second primary malignancies (SPMs). From 1989 to 2015, we identified 29,631 cancer patients and 62,863 healthy family members. We calculated the standardized incident ratios (SIRs) of early-onset primary cancers diagnosed in proband siblings and mothers, as well as SPMs detected among early-onset patients. Analyses were stratified by self-identified race/ethnicity. Results: Given probands with cancer, there were increased relative risks of any cancer for siblings and mothers (SIR = 3.32; 95% confidence interval [CI]: 2.85-3.85) and of SPMs (SIR = 7.27; 95% CI: 6.56-8.03). Given a proband with solid cancer, both Latinos (SIR = 4.98; 95% CI: 3.82-6.39) and non-Latino Blacks (SIR = 7.35; 95% CI: 3.36-13.95) exhibited significantly higher relative risk of any cancer in siblings and mothers when compared to non-Latino White subjects (SIR = 3.02; 95% CI: 2.12-4.16). For hematologic cancers, higher familial risk was evident for Asian/Pacific Islanders (SIR = 7.56; 95% CI: 3.26-14.90) compared to non-Latino whites (SIR = 2.69; 95% CI: 1.62-4.20). Conclusions: The data support a need for increased attention to the genetics of early-onset cancer predisposition and environmental factors in race/ethnic minority families in the United States. Funding: This work was supported by the V Foundation for funding this work (Grant FP067172).

Applying Four-Step Characteristic Ion Filtering with HPLC-Q-Exactive MS/MS Spectrometer Approach for Rapid Compound Structures Characterization and Major Representative Components Quantification in Modified Tabusen-2 Decoction.

Modified Tabusen-2 decoction (MTBD) is traditional Chinese Mongolia medicine, mainly used to treat osteoporosis. However, the precise material basis of this prescription is not yet fully elucidated. Herein, we establish an HPLC-Q-Exactive MS/MS spectrometer method with four-step characteristic ion filtering (FSCIF) strategy to quickly and effectively identify the structural features of MTBD and determine the representative compounds content. The FSCIF strategy included database establishment, characteristic ions summarization, neutral loss fragments screening, and secondary mass spectrum fragment matching four steps. By using this strategy, a total of 143 compounds were unambiguously or tentatively annotated, including 5 compounds which were first reported in MTBD. Nineteen representative components were simultaneously quantified with the HPLC-Q-Exactive MS/MS spectrometer, and it is suitable for eight batches of MTBD. Methodology analysis showed that the assay method had good repeatability, accuracy, and stability. The method established above was successfully applied to assess the quality of MTBD extracts. Collectively, our findings enhance our molecular understanding of the MTBD formulation and will allow us to control its quality in a better way. At the same time, this study can promote the development and utilization of ethnic medicine.

Trends in Acute Lymphoblastic Leukemia Incidence in the United States by Race/Ethnicity From 2000 to 2016.

Incidence trends in acute lymphoblastic leukemia (ALL) demonstrate disparities by race and ethnicity. We used data from the Surveillance, Epidemiology, and End Results Registry to evaluate patterns in ALL incidence from 2000 to 2016, including the association between percentage of people born in a foreign country at the county level and ALL incidence. Among 23,829 persons of all ages diagnosed with ALL, 8,297 (34.8%) were Latinos, 11,714 (49.2%) were non-Latino (NL) Whites, and 1,639 (6.9%) were NL Blacks. Latinos had the largest increase in the age-adjusted incidence rate (AAIR) of ALL during this period compared with other races/ethnicities for both children and adults: The AAIR was 1.6 times higher for Latinos (AAIR = 2.43, 95% confidence interval (CI): 2.37, 2.49) than for NL Whites (AAIR = 1.56, 95% CI: 1.53, 1.59) (P < 0.01). The AAIR for all subjects increased approximately 1% per year from 2000 to 2016 (annual percent change = 0.97, 95% CI: 0.67, 1.27), with the highest increase being observed in Latinos (annual percent change = 1.18, 95% CI: 0.76, 1.60). In multivariable models evaluating the contribution of percentage of county residents who were foreign-born to ALL risk, a positive association was found for percentage foreign-born for NL Whites (P for trend < 0.01) and NL Blacks (P for trend < 0.01), but the reverse was found for Latinos (P for trend < 0.01); this is consistent with tenets of the "Hispanic paradox," in which better health outcomes exist for foreign-born Latinos.

Pediatric glioma and medulloblastoma risk and population demographics: a Poisson regression analysis.

BACKGROUND: The incidence of pediatric brain tumors varies by race and ethnicity, but these relationships may be confounded by socioeconomic status (SES). In this study, the Surveillance, Epidemiology, and End Results Program (SEER) database was evaluated for associations between race/ethnicity and pediatric glioma and medulloblastoma risk with adjustment for SES. METHODS: Pediatric glioma and medulloblastoma cases from the SEER database (years: 2000-2016) were included. Differences in incidence rates by ethnicity, sex, age, and SES-related factors were evaluated by calculation of age-adjusted incidence rates (AAIRs) and annual percent change (APC). SES-related factors (percentage without less than high school graduation, median household income, and percentage foreign-born) were derived from the census at the county-level (year: 2000). Multivariable Poisson regression models with adjustment for selected covariates were constructed to evaluate risk factors. RESULTS: The highest AAIRs of pediatric glioma were observed among non-Hispanic Whites (AAIR: 2.91 per 100 000, 95%-CI: 2.84-2.99). An increasing incidence of pediatric glioma by calendar time was observed among non-Hispanic Whites and non-Hispanic Blacks (APC: 0.97%, 95%-CI: 0.28-1.68 and APC: 1.59%, 95%-CI: 0.03-3.18, respectively). Hispanic and non-Hispanic Black race/ethnicity was associated with lower risk when compared with non-Hispanic White (incidence rate ratios [IRRs]: 0.66, 95%-CI: 0.63-0.70; and 0.69, 95%-CI: 0.65-0.74, respectively). For medulloblastoma, the highest AAIR was observed for non-Hispanic Whites with a positive APC (1.52%, 95%-CI: 0.15-2.91). Hispanics and non-Hispanic Blacks had statistically significant lower IRRs compared with non-Hispanic Whites (IRRs: 0.83, 95%-CI: 0.73-0.94; and 0.72, 95%-CI: 0.59-0.87, respectively). CONCLUSION: Non-Hispanic White race/ethnicity was associated with higher pediatric glioma and medulloblastoma IRRs in models with adjustments for SES.

Birth Characteristics and Risk of Early-Onset Synovial Sarcoma.

BACKGROUND: Synovial sarcoma is a rare cancer with peak incidence in the young adult period. Despite poor outcomes of this aggressive cancer, there is little epidemiologic research addressing its etiology. METHODS: We collected birth characteristic data on synovial sarcoma cases born during 1978-2015 and diagnosed during 1988-2015 in California (n = 244), and 12,200 controls frequency-matched on year of birth. We also constructed a dataset of cancer cases in siblings of sarcoma subjects to assess familial risk. RESULTS: In multivariable logistic regression analyses, synovial sarcoma was more frequent in Hispanics compared with non-Hispanic whites [OR, 1.48; 95% confidence interval (CI), 1.06-2.08]. Higher birth weight was a risk factor in Hispanics; each 500 g increase in birth weight was associated with a 22% increase in disease risk (OR, 1.22; 95% CI, 1.00-1.48). Also, a strong role for birth order was suggested, with highest risk for the first born (second child compared with first: OR, 0.61; 95% CI, 0.44-0.84; third or later compared with first: OR, 0.53; 95% CI, 0.36-0.77). Siblings of patients with synovial sarcoma did not display elevated cancer incidence, suggesting the low likelihood that strong familial predisposition alleles play a significant role in this disease. CONCLUSIONS: The associations with birth weight and birth order suggest that nutritional, developmental, and environmental factors may play a role in the etiology of synovial sarcoma. IMPACT: Further epidemiologic research on synovial sarcoma should evaluate epigenetic and developmental mechanisms and the formation of the archetypical t(X;18) translocation that defines this disease.

Longitudinal antibiotic prescribing trends among US dental specialists within a pharmacy benefits manager, 2013 through 2015.

BACKGROUND: Reducing inappropriate antibiotic prescriptions (Rxs) is a major quality improvement initiative in the United States. Tracking antibiotic prescribing trends is 1 method of assessing improvement in antibiotic prescribing. The purpose of this study was to assess longitudinal antibiotic prescribing practices among dental specialists. METHODS: This was a retrospective ecological longitudinal trend study. The authors calculated monthly systemic antibiotic Rx counts, and rates per 100,000 beneficiaries, from a pharmacy benefits manager in the United States from 2013 through 2015. The authors calculated average annual antibiotic Rx rates (AARs) for the 3-year study period. The authors used a quasi-Poisson regression model to analyze antibiotic Rx trends. The authors quantified seasonal trends, when present, via peak-to-trough ratios (PTTRs). RESULTS: Dental specialists prescribed 2.4 million antibiotics to the cohort of 38 million insurance beneficiaries during the 3-year study period (AAR = 2,086 Rxs per 100,000 beneficiaries). Oral and maxillofacial surgeons prescribed the most antibiotics (1,172,104 Rxs; AAR = 1,018 Rxs per 100,000 beneficiaries), followed by periodontists (527,038 Rxs; AAR = 457 Rxs per 100,000 beneficiaries), and endodontists (447,362 Rxs; AAR = 388 Rxs per 100,000 beneficiaries). Longitudinal antibiotic prescribing trends were stable among all dental specialties in the regression models (P > .05). The authors observed substantial seasonal variation in antibiotic Rxs in 2 specialties: pediatric dentistry (PTTR, 1.18; 95% confidence interval, 1.13 to 1.25) and orthodontics and dentofacial orthopedics (PTTR, 1.41; 95% confidence interval, 1.21 to 1.71), with the highest rates of antibiotic Rxs in the spring and winter. CONCLUSIONS: Antibiotic prescribing practices for dental specialists remained stable. The authors observed seasonal trends in 2 specialties. PRACTICAL IMPLICATIONS: Public health efforts are needed improve antibiotic prescribing among dental specialties.

Rural/urban residence and childhood and adolescent cancer survival in the United States.

BACKGROUND: To the authors' knowledge, no previous study has examined the relationship between rural/urban residence and childhood or adolescent cancer survival in the United States. Using the Surveillance, Epidemiology, and End Results 18 registries database, the authors examined childhood and adolescent cancer survival by rural/urban residence as defined by Rural-Urban Continuum Codes (RUCCs). METHODS: The authors obtained data from Surveillance, Epidemiology, and End Results 18 registries for individuals diagnosed at ages birth to 19 years with a first primary malignant cancer from 2000 through 2010. Rural/urban residence at the time of diagnosis was defined using both metropolitan/nonmetropolitan county classifications and individual RUCC categories. Cox proportional hazards regression was used to compute adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between rural/urban residence and cancer survival. The authors also examined effect modification by age group, sex, race/ethnicity, and cancer type. RESULTS: Among 41,879 cancer cases, approximately 54.7% were non-Hispanic white, 54.3% were male, and 90.4% lived in a metropolitan county. Individuals living in nonmetropolitan counties versus metropolitan counties had a similar risk of cancer death (HR,  1.03; 95% CI, 0.94-1.13) as did those living in nonmetropolitan rural counties with <2500 individuals nonadjacent to a metropolitan area versus those living in metropolitan counties of ≥1 million individuals (HR,  0.98; 95% CI, 0.71-1.37). Evidence for effect modification largely was absent. CONCLUSIONS: The results of the current study suggest that childhood and adolescent cancer survival in the United States does not vary by rural/urban residence at the time of diagnosis as defined by RUCCs. The widespread availability of public health insurance for children and adolescents and a nationwide network of pediatric cancer providers may explain this finding.

Characteristics of The Cancer Genome Atlas cases relative to U.S. general population cancer cases.

BACKGROUND: Despite anecdotal reports of differences in clinical and demographic characteristics of The Cancer Genome Atlas (TCGA) relative to general population cancer cases, differences have not been systematically evaluated. METHODS: Data from 11,160 cases with 33 cancer types were ascertained from TCGA data portal. Corresponding data from the Surveillance, Epidemiology, and End Results (SEER) 18 and North American Association of Central Cancer Registries databases were obtained. Differences in characteristics were compared using Student's t, Chi-square, and Fisher's exact tests. Differences in mean survival months were assessed using restricted mean survival time analysis and generalised linear model. RESULTS: TCGA cases were 3.9 years (95% CI 1.7-6.2) younger on average than SEER cases, with a significantly younger mean age for 20/33 cancer types. Although most cancer types had a similar sex distribution, race and stage at diagnosis distributions were disproportional for 13/18 and 25/26 assessed cancer types, respectively. Using 12 months as an end point, the observed mean survival months were longer for 27 of 33 TCGA cancer types. CONCLUSIONS: Differences exist in the characteristics of TCGA vs. general population cancer cases. Our study highlights population subgroups where increased sample collection is warranted to increase the applicability of cancer genomic research results to all individuals.

Assessment of inappropriate antibiotic prescribing among a large cohort of general dentists in the United States.

BACKGROUND: The purpose of this study was to assess dental antibiotic prescribing trends over time, to quantify the number and types of antibiotics dentists prescribe inappropriately, and to estimate the excess health care costs of inappropriate antibiotic prescribing with the use of a large cohort of general dentists in the United States. METHODS: We used a quasi-Poisson regression model to analyze antibiotic prescriptions trends by general dentists between January 1, 2013, and December 31, 2015, with the use of data from Express Scripts Holding Company, a large pharmacy benefits manager. We evaluated antibiotic duration and appropriateness for general dentists. Appropriateness was evaluated by reviewing the antibiotic prescribed and the duration of the prescription. RESULTS: Overall, the number and rate of antibiotic prescriptions prescribed by general dentists remained stable in our cohort. During the 3-year study period, approximately 14% of antibiotic prescriptions were deemed inappropriate, based on the antibiotic prescribed, antibiotic treatment duration, or both indicators. The quasi-Poisson regression model, which adjusted for number of beneficiaries covered, revealed a small but statistically significant decrease in the monthly rate of inappropriate antibiotic prescriptions by 0.32% (95% confidence interval, 0.14% to 0.50%; P = .001). CONCLUSIONS: Overall antibiotic prescribing practices among general dentists in this cohort remained stable over time. The rate of inappropriate antibiotic prescriptions by general dentists decreased slightly over time. PRACTICAL IMPLICATIONS: From these authors' definition of appropriate antibiotic prescription choice and duration, inappropriate antibiotic prescriptions are common (14% of all antibiotic prescriptions) among general dentists. Further analyses with the use of chart review, administrative data sets, or other approaches are needed to better evaluate antibiotic prescribing practices among dentists.

An evaluation of dental antibiotic prescribing practices in the United States.

BACKGROUND: Antibiotic prescribing practices among general dentists and dental specialists in the United States remains poorly understood. The purpose of this study was to compare prescribing practices across dental specialties, evaluate the duration of antibiotics dentists prescribed, and determine variation in antibiotic selection among dentists. METHODS: The authors performed a retrospective cross-sectional analysis of dental care provider specialties linked to deidentified antibiotic claims data from a large pharmacy benefits manager during the 2015 calendar year. RESULTS: As a group, general dentists and dental specialists were responsible for more than 2.9 million antibiotic prescriptions, higher than levels for several other medical and allied health care provider specialties. Antibiotic treatment duration generally was prolonged and commonly included broad-spectrum agents, such as amoxicillin clavulanate and clindamycin. Although amoxicillin was the most commonly prescribed antibiotic among all dental specialties, there was substantial variation among other antibiotics each specialty selected. The most common antibiotic treatment durations were 7 and 10 days. CONCLUSIONS: This study's results demonstrate that dentists frequently prescribe antibiotics for prolonged periods and often use broad-spectrum antibiotics. Further studies are necessary to evaluate the appropriateness of these antibiotic prescribing patterns. PRACTICAL IMPLICATIONS: The clinically significant variation in antibiotic selection and treatment duration identified among all dental specialties in this study population implies that further research and guidance into the treatment of dental infections is necessary to improve and standardize antibiotic prescribing practices.

Pediatric cancer risk in association with birth defects: A systematic review.

BACKGROUND: Many epidemiological studies have examined associations between birth defects (BDs) and pediatric malignancy over the past several decades. Our objective was to conduct a systematic literature review of studies reporting on this association. METHODS: We used librarian-designed searches of the PubMed Medline and Embase databases to identify primary research articles on pediatric neoplasms and BDs. English language articles from PubMed and Embase up to 10/12/2015, and in PubMed up to 5/12/2017 following an updated search, were eligible for inclusion if they reported primary epidemiological research results on associations between BDs and pediatric malignancies. Two reviewers coded each article based on the title and abstract to identify eligible articles that were abstracted using a structured form. Additional articles were identified through reference lists and other sources. Results were synthesized for pediatric cancers overall and for nine major pediatric cancer subtypes. RESULTS: A total of 14,778 article citations were identified, of which 80 met inclusion criteria. Pediatric cancer risk was increased in most studies in association with BDs overall with some notable specific findings, including increased risks for CNS tumors in association with CNS abnormalities and positive associations between rib anomalies and several pediatric cancer types. CONCLUSIONS: Some children born with BDs may be at increased risk for specific pediatric malignancy types. This work provides a foundation for future investigations that are needed to clarify specific BD types predisposing toward malignancy and possible underlying causes of both BDs and malignancy.