Racial and Ethnic Disparities in Risk and Survival in Children With Neuroblastoma: A Children's Oncology Group Study

Henderson, Tara O.; Bhatia, Smita; Pinto, Navin; London, Wendy B.; McGrady, Patrick; Crotty, Catherine; Sun, Can‐Lan; Cohn, Susan L.

doi:10.1200/jco.2010.29.6103

Cited by 110 publications

(103 citation statements)

References 26 publications

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“…Neuroblastoma is also the most common cancer diagnosed in infants and occurs slightly more often in boys than girls. African American and Native American patients are more likely to have more aggressive disease with lower survival rates, although the etiologies of these differences are unclear [5].…”

Section: Epidemiology and Geneticsmentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

300

253

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Introduction: Children with neuroblastoma have widely divergent outcomes, ranging from cure in >90% of patients with low risk disease to <50% for those with high risk disease. Recent research has shed light on the biology of neuroblastoma, allowing for more accurate risk stratification and treatment reduction in many cases, although newer treatment strategies for children with high-risk and relapsed neuroblastoma are needed to improve outcomes. Areas covered: Neuroblastoma epidemiology, diagnosis, risk stratification, and recent advances in treatment of both newly diagnosed and relapsed neuroblastoma. Expert commentary: The identification of newer tumor targets and of novel cell-mediated immunotherapy agents may lead to novel therapeutic approaches, and clinical trials for regimens designed to target individual genetic aberrations in tumors are underway. A combination of therapeutic modalities will likely be required to improve survival and cure rates for patients with high-risk neuroblastoma.ARTICLE HISTORY

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Section: Epidemiology and Geneticsmentioning

confidence: 99%

Overview and recent advances in the treatment of neuroblastoma

Whittle

Smith

Doherty

et al. 2017

Expert Review of Anticancer Therapy

300

253

View full text Add to dashboard Cite

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“…The rarity or absence of the protective allele in African populations and its relative depletion in African-Americans may partially explain the more aggressive clinical course in African-American children 29 . Moreover, this work further confirms the utility of association studies to define clinically relevant oncogenic pathways.…”

mentioning

confidence: 99%

Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism

Oldridge

Wood

Weichert-Leahey

et al. 2015

Nature

261

268

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Summary Neuroblastoma is a pediatric malignancy that typically arises in early childhood and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumors with excellent outcomes to widely metastatic disease where long-term survival is approximately 40% despite intensive therapy1. A previous genome-wide association study (GWAS) identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumor cells2. Here we sought to discover the causal DNA variant at this locus and the mechanism by which it leads to neuroblastoma tumorigenesis. We first imputed all possible genotypes across the LMO1 locus and then mapped highly associated single nucleotide polymorphism (SNPs) to areas of chromatin accessibility, evolutionary conservation, and transcription factor binding sites. SNP rs2168101 G>T was the most highly associated variant (combined P=7.47×10-29, Odds Ratio 0.65, 95% CI: 0.60-0.70) and resided in a super-enhancer defined by extensive acetylation of histone H3 lysine 27 within the first intron of LMO1. The ancestral G-allele that is associated with tumor formation resides in a conserved GATA transcription factor binding motif. We show that the newly evolved protective TATA allele is associated with decreased total LMO1 expression (P=0.028) in neuroblastoma primary tumors and ablates GATA3 binding (P<0.0001). We demonstrate allelic imbalance favoring the G-containing strand in tumors heterozygous for this SNP as demonstrated both by RNA sequencing (P<0.0001) and reporter assays (P=0.002). These findings show that a recently evolved polymorphism within a super-enhancer element in the first intron of LMO1 influences neuroblastoma susceptibility through differential GATA transcription factor binding and direct modulation of LMO1 expression in cis, and this leads to an oncogenic dependency in tumor cells.

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“…However, most of these studies failed to account for environmental and socioeconomic differences between the groups. Only a few studies evaluated patients with solid tumors [7,8] and even fewer studies examined the impact of SES or access to care on pediatric cancer burden and outcome [3,9–12]. …”

mentioning

confidence: 99%

Health disparities are important determinants of outcome for children with solid tumor malignancies

Austin

Nguyen

Eberth

et al. 2015

Journal of Pediatric Surgery

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Purpose The purpose of this study was to identify health disparities in children with non-CNS solid tumor malignancies and examine their impact on disease presentation and outcome. Methods We examined the records of all children (age ≤ 18 years) diagnosed with a non-CNS solid tumor malignancy and enrolled in the Texas Cancer Registry between 1995 and 2009 (n = 4603). The primary outcome measures were disease stage and overall survival (OS). Covariates included gender, age, race/ethnicity, year of diagnosis, socioeconomic status (SES), and driving distance to the nearest pediatric cancer treatment facility. Statistical analyses included life table methods, logistic, and Cox regression. Statistical significance was defined as p < 0.05. Results Children with advanced-stage disease were more likely to be male, <10 years old, and Hispanic or non-Hispanic Blacks (all p < 0.05). Distance to treatment and SES did not impact stage of disease at presentation. However, Hispanic and non-Hispanic Blacks and patients in the lowest SES quartile had the worst 1- and 5-year survival (all p < 0.05). The adjusted OS differed by age, race, and stage, but not SES or distance to the nearest treatment facility. Conclusions Race/ethnicity plays an important role in survival for children with non-CNS solid tumor malignancies. Future work should better define these differences to establish mechanisms to decrease their impact.

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Racial and Ethnic Disparities in Risk and Survival in Children With Neuroblastoma: A Children's Oncology Group Study

Cited by 110 publications

References 26 publications

Overview and recent advances in the treatment of neuroblastoma

Overview and recent advances in the treatment of neuroblastoma

Genetic predisposition to neuroblastoma mediated by a LMO1 super-enhancer polymorphism

Health disparities are important determinants of outcome for children with solid tumor malignancies

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