Neurofibromatosis Type 1 as a model population for pediatric brain cancer prevention and control research

A major barrier to progress in pediatric brain cancer prevention and treatment is the lack of understanding of factors that influence its development and prognosis. This limitation is especially relevant to pediatric brain tumors, where few environmental or genetic risk factors have been identified. Studies conducted in individuals with cancer syndromes may increase our understanding of pediatric brain tumor causes and poor outcomes. In this study, we will employ an inherited tumor predisposition syndrome (neurofibromatosis type 1; NF1) to study risk factors for pediatric brain cancer. NF1 represents an ideal high-risk study population with 15-20% of affected individuals developing low-grade pediatric brain tumors, the second most common cancer type in children without NF1. Similar to the general population of children with pediatric brain tumors, the underlying reasons for brain tumor development in children with NF1 are unknown. The essential first step in identifying factors that predict pediatric brain tumor development and poor outcomes is to establish a large international dataset of individuals with NF1. To achieve this goal, we propose three aims: (1) to implement several different recruitment strategies to recruit individuals with NF1 to an internet-based registry, (2) to confirm NF1 diagnoses in registry participants, and (3) to use registry data to identify risk factors for pediatric brain tumors for further study. This study will provide the foundation for research studies that will advance our understanding of the causes of brain cancer in children.

Progress Reports and Updates

Project Update

"About 1 in 7 children with NF1 will develop a brain tumor due to a genetic mutation in their NF1 gene that they carry in every cell of their body. Despite the extremely high risk for pediatric brain tumors, it is completely unknown why only some children develop brain tumors. ALSF is helping us to figure this out by supporting research that we hope will lead to new breakthroughs in understanding differences between individuals with NF1 who develop brain tumors and those who do not.” -Kimberly Johnson Ph.D.

We spoke with June 2014 Featured Researcher Kimberly Johnson, Ph.D. about her research developments on her funded 2012 Epidemology Grant:

In simple terms, how would you describe this project?
This project represents one of the first steps to conducting large scale studies of pediatric brain tumor etiology in NF1. There are no population registries that would provide a contact list for assembling individuals with NF1 for participation in research. Our project evaluated a number of different methods, including social media advertising and working with advocacy groups, for recruiting individuals with NF1 from across the world to an online patient registry. We found that online recruiting through Facebook and Google were highly effective means of rapidly assembling individuals with NF1 for research studies.

What does this mean for children with cancer and their families?
Children with the cancer syndrome Neurofibromatosis Type 1 (NF1) have an extremely high risk of brain tumors, with between 1 in 5-10 children with NF1 developing an optic glioma (a type of brain tumor) before the age of 10 years. Currently clinicians have no way of predicting who will develop a brain tumor in children with NF1. This can be extremely worrying to families. We are trying to determine factors that distinguish children who develop brain tumors in NF1 from those who do not develop brain tumors. If some of these factors are modifiable, we may be able to reduce the number of children with NF1 who develop brain tumors. In addition to potentially having a direct impact on the clinical care of children and families dealing with NF1, our work may also have implications for understanding risk factors for pediatric brain tumors in the general population. The extreme sensitivity of children with NF1 to the development of brain tumors may help us better distinguish signals from noise that can be difficult to tease out in studies of children who are not strongly genetically predisposed to brain tumor development.

Your project involves social media and online advertising, things we don’t usually associate with cancer research. What caused you to pursue this project?
It is estimated that over two billion people across the world use the internet. The globalization of communication has provided cancer researchers with new opportunities to access populations of individuals for research participation that have historically been hard to reach. We saw this as an extraordinary opportunity to assemble individuals with NF1 for large studies of pediatric brain tumors and other health outcomes that impact this population. In addition to being able to conduct larger studies than previously possible, the online format of the registry allows individuals to participate in research who have not previously had access to research studies.

Has this research been published?
To date, we have published two papers about the registry and we currently have a couple of major research projects involving pediatric brain tumor risk factors underway. These projects have been made possible because of the work described in these publications.

Johnson KJ, Mueller NL, Williams K, Gutmann DH. Evaluation of participant recruitment methods to a rare disease online registry. 2014 Apr 3 Am J Med Genet A PMID: 24700441
Johnson KJ, Hussain I, Williams K, Santens R, Mueller N, Gutmann DH. Development of an International Internet-Based Neurofibromatosis Type 1 Patient Registry. Contemp Clin Trials. 2012 Dec 14. PMID: 23246715

What did this grant from ALSF allow you to do that you wouldn’t have been able to do otherwise?
We wouldn’t have been able to assemble such a large number of individuals with a pediatric brain tumor syndrome (>500 children with NF1) for research that aims to identify pediatric brain tumor causes in such a short amount of time without the support of ALSF. We are excited about the pediatric brain tumor research that has now been made possible through the generosity of the ALSF community.

What attracted you to this field/topic initially?
I have had a long standing interest in cancer (especially brain tumors) and human genetics. I have always been passionate about conducting research that makes a difference to families, especially families with children affected with serious diseases. As a parent, I can only imagine how much courage and strength it takes to help your child through a serious life-threatening disease. Childhood cancer also affected my family when my niece who is now 15 was diagnosed with retinoblastoma at the age of 2 years. This experience bolstered my commitment to spending my career conducting this type of research. My heart goes out daily to families affected by childhood cancer.

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