Racial/Ethnic Differences in Pediatric Brain Tumor Diagnoses in Patients with Neurofibromatosis Type 1

Abadin, Salmafatima S.; Zoellner, N; Schaeffer, M. A.; Porcelli, Bree A.; Gutmann, David H.; Johnson, Kimberly

doi:10.1016/j.jpeds.2015.04.076

Cited by 26 publications

(15 citation statements)

References 34 publications

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“…Glioma risk factors, and specifically OPGs, in NF1 are not well-defined. A number of studies have reported that individuals with European ancestry are more likely to be diagnosed with an OPG than those with other ancestries [5–10]. In addition, the results of two small studies suggest that children with NF1 gene mutations occurring toward the 5′ end are more likely to develop an OPG [11,12].…”

Section: Introductionmentioning

confidence: 99%

Peri-gestational risk factors for pediatric brain tumors in Neurofibromatosis Type 1

Johnson

Zoellner

Gutmann

2016

Cancer Epidemiology

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Background Individuals with Neurofibromatosis Type 1 (NF1) are strongly predisposed to developing pediatric brain tumors (PBTs), especially optic pathway gliomas (OPGs). Although developmental factors have been implicated in the origins of PBTs in both human and animal studies, associations between early-life factors and PBTs have not been evaluated in individuals with NF1. Our objective was to evaluate associations between peri-gestational characteristics and PBTs in this population. Methods We conducted a cross-sectional study, ascertaining questionnaire and medical record data for 606 individuals <18 years old who enrolled in the NF1 Patient Registry Initiative (NPRI) from 6/9/2011-6/29/2015. One hundred eighty-four individuals had reported PBT diagnoses, including 65 who were identified with OPG diagnoses. Cox proportional hazards regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between PBT and OPG diagnoses and peri-gestational characteristics (prematurity, birth weight, parental age, plurality, family history of NF1, assisted reproductive technology, maternal vitamin supplementation, and parental smoking). Results We observed no significant associations between any of the assessed characteristics and PBTs overall or OPGs with the exception of birth weight. After controlling for potential confounding variables, we observed a significant positive association between birth weight quartile and OPGs with a HR of 3.32 (95% CI 1.39–7.94) for the fourth (≥3915.5 g) compared to the first (≤3020 g) quartile (p for trend = 0.001). Conclusions Consistent with results for PBTs in the general population, these results suggest that higher birth weights increase OPG risk in individuals with NF1.

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Section: Introductionmentioning

confidence: 99%

Peri-gestational risk factors for pediatric brain tumors in Neurofibromatosis Type 1

Johnson

Zoellner

Gutmann

2016

Cancer Epidemiology

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“…Of note, our previous studies suggest that NF1 [23] and PBT diagnoses are reported with good accuracy for NPRI participants [13]. For allergic condition diagnoses, participant/parent legal guardian reported data could result in misclassification of subjects with respect to allergic condition diagnoses if conditions are not actually present in the participant or they are present and not reported.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to informing the underlying biology of PBTs, identification of factors that modulate risk is a critical component of developing PBT risk prediction models for this population and for developing prevention strategies. To date, some studies have indicated that individuals with African ancestry are at lower risk of PBT development than those with European ancestry [8–13] and two small studies have suggested that children harboring NF1 gene mutations closer to its 5′ end are more likely to develop OPGs [14, 15]. …”

Section: Introductionmentioning

confidence: 99%

Associations between allergic conditions and pediatric brain tumors in Neurofibromatosis type 1

et al. 2015

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Background Individuals with Neurofibromatosis type 1 (NF1) are at increased risk for pediatric brain tumors (PBTs), especially optic gliomas; however, factors influencing their development are largely unknown. Extensive research suggests that allergic conditions protect against brain tumors, particularly gliomas in individuals without NF1. In this large cross-sectional study, we employed two different data sources to evaluate evidence for the hypothesis that allergic conditions (allergies, asthma, and eczema) may protect against PBT development in individuals with NF1. Methods We used self- and parent/legal guardian reported questionnaire data from participants in the NF1 Patient Registry Initiative (NPRI, n=1660) born from 1933–2014 to ascertain allergic condition and PBT diagnosis histories. Medical records (MRs) of 629 NF1 patients at a large medical center born from 1930–2012 were also reviewed for PBT and allergic condition diagnoses to evaluate additional evidence for our hypothesis. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between allergic condition diagnoses and PBTs. Results Both data sources provided limited to no support for a protective effect of allergies or eczema on PBT development. Non-significant inverse associations between asthma and PBTs were observed (NPRI: OR=0.80, 95% CI 0.55–1.17; MR: OR=0.71, 95% CI 0.40–1.28) with stronger associations for optic gliomas specifically. Additionally, a significant inverse association was observed in an NPRI subgroup analysis where the reported asthma diagnosis age was younger than the reported PBT diagnosis age (OR=0.57; 95% CI 0.36–0.89). Conclusion Our study supports the hypothesis that asthma protects against PBT development in NF1.

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“…While there is evidence for differences in racial and ethnic group risks for brain tumors [63], the most compelling data to support the existence of modifier loci derives from Nf1 genetically-engineered mouse models [64]. In these studies, NPcis mice, which carry mutations in the Nf1 and Trp53 genes on the same chromosome, develop HGG.…”

Section: Genomic/genetic Levelmentioning

confidence: 99%

Contextual signaling in cancer

Smithson

Anastasaki

Chen

et al. 2016

Seminars in Cell & Developmental Biology

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The formation and maintenance of an organism is highly dependent on the orderly control of cell growth, differentiation, death, and migration. These processes are tightly regulated by signaling cascades in which a limited number of molecules dictate these cellular events. While these signaling pathways are highly conserved across species and cell types, the functional outcomes that result from their engagement are specified by the context in which they are activated. Using the Neurofibromatosis type-1 (NF1) cancer predisposition syndrome as an illustrative platform, we discuss how NF1/RAS signaling can create functional diversity at multiple levels (molecular, cellular, tissue, and genetic/genomic). As such, the ability of related molecules (e.g., K-RAS, H-RAS) to activate distinct effectors, as well as cell type- and tissue-specific differences in molecular composition and effector engagement, generate numerous unique functional effects. These variations, coupled with a multitude of extracellular cues and genomic/genetic changes that each modify the innate signaling properties of the cell, enable precise control of cellular physiology in both health and disease. Understanding these contextual influences is important when trying to dissect the underlying pathogenic mechanisms of cancer relevant to molecularly-targeted therapeutics.

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Racial/Ethnic Differences in Pediatric Brain Tumor Diagnoses in Patients with Neurofibromatosis Type 1

Cited by 26 publications

References 34 publications

Peri-gestational risk factors for pediatric brain tumors in Neurofibromatosis Type 1

Peri-gestational risk factors for pediatric brain tumors in Neurofibromatosis Type 1

Associations between allergic conditions and pediatric brain tumors in Neurofibromatosis type 1

Contextual signaling in cancer

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