Neuroblastoma Epidemiology in North America

NENA (Neuroblastoma Epidemiology in North America)

 
Andy Olshan
Message From the Principal Investigator of the NENA Study
Now that our primary study enrollment has been completed for the NENA Study, I want to take this opportunity to express my heartfelt appreciation for all of you who spent time answering questions, obtaining samples, and talking with our staff.  We are very excited to reach this point in the study.  We are now moving on to process the samples and questionnaire data.  This phase of the study make take a little while so we can be sure we have the highest quality data and analysis.  We are looking forward to seeing what exciting results may help us better understand the causes of neuroblastoma and how it might be prevented in the future.  We will use this website to keep you posted.  Again, my thanks for all you have done.
Andrew F. Olshan , PhD
 
Neuroblastoma (NB) is a tumor of the peripheral nervous system. It is the most common malignancy of infancy. Neruoblastoma is typically diagnosed in very young children, which suggests that events occurring during the prenatal period may play an important role in the development of this disease. Several epidemiologic studies have reported that maternal vitamin intake during pregnancy reduces the risk of neuroblastoma. It is also thought that genetics may increase or decrease the risk of this disease.
 
NENA (Neuroblastoma Epidemiology in North America) is one of the largest epidemiologic research studies to date that examines the relationship of neuroblastoma to exposures during pregnancy and genetic susceptibilities. Over a five-year period, NENA seeks to enroll approximately 600 children (living and deceased) who were diagnosed with neuroblastoma before 6 years of age. In addition, NENA is enrolling the biological mothers and biological fathers of these children. In this way, biological triads can be studied which allows NENA to explore the genetics of the disease. Children with neuroblastoma, along with their biological parents, are recruited from the US, Puerto Rico and Canada to participate in this research.
 
NENA is approved by the Children’s Oncology Group (COG)-Protocol #AEP107N1. Cases for NENA are identified via the Childhood Cancer Research Network (CCRN), a North American childhood cancer registry system that is directed by COG. Eligibility for NENA requires that a family has both registered with COG and consented to being contacted for non-therapeutic studies.
 
Families participate in the NENA Study from their own homes. All study materials and Specimen collection kits are mailed to participants’ home addresses, completed by participants at home, and returned in prepaid mailers back to the study site.
 
Biological mothers and fathers each use a spit-tube kit to collect their own saliva. Parents or guardians who consent to their child’s participation obtain a saliva sample from their child using a special sponge kit designed for use with young children. These samples are then analyzed at the lab for genetic susceptibilities to neuroblastoma. For deceased children enrolled in the study, a tissue specimen is available for genetic analysis from the COG Neuroblastoma Biology Protocol DNA Bank-Protocol ANBLOOB1. Parents of deceased children are asked to sign a parental consent form, which allows NENA to obtain this sample.
 
Participating mothers in the research study are also provided with a paper/pen questionnaire to complete. This questionnaire asks them about exposures that may have occurred during their pregnancy with their child with neuroblastoma. Mothers are asked questions about their health, their pregnancy and medical history, any family cancer history, their intake of certain foods, drinks, and vitamins, and the child’s early feeding habits.
 
Unlike a clinical trial or hospital-based study, participating children or adults are not asked to take drugs or medicine of any kind, and the child’s neuroblastoma will not be treated. Joining this study is voluntary and separate from the child’s treatment, and families do not have to be involved with this non-therapeutic research in order for their child to receive medical treatment. Individuals may refuse to join, or may withdraw consent to be in the study, for any reason and at any time, without penalty.
 
Information resulting from NENA will contribute to scientific knowledge about neuroblastoma and, hopefully help children and families in the future who are dealing with the disease.
 
 
NENA General Study Brochure PDF for NENA
 
 
Principal Investigator
Andrew F. Olshan, PhD
University of North Carolina
Gillings School of Global Public Health
Department of Epidemiology
2101B McGavran-Greenberg Hall
Chapel Hill, NC 27599-7435
Sponsors
National Institutes of Health
National Cancer Institute

If you have questions or would like more information about the NENA study, please contact:

Kathryn Carrier, MPH
Project Director
Phone: 919-966-3000
Email: kathryn_carrier@unc.edu

or

Elyssa Trani, MS
Research Assistant
Phone: 919-966-1635
Email: elyssa_trani@unc.edu

Toll-Free Number:
1-877-658-1623

Email: nena_study@unc.edu

Address:
University of North Carolina Dept of Epidemiology
137 East Franklin Street
Suite 32, CB 8050
Chapel Hill, NC 27599-8050

Staff & Investigators Login

 
ELIGIBILITY REQUIREMENTS

Thank you for your interest in the NENA Study. In order for our research to be effective, certain eligibility requirements must be met before we can enroll individuals or families into our study.

If you have received mailings and/or phone calls directly from the NENA Study inviting you to participate, you are most likely eligible. Please respond to the study by email/phone or by returning the Interest Form in your mailing.

If you have not been contacted by the study, the following 6 conditions MUST be met in order to be eligible for participation:

  1. Your child was diagnosed with neuroblastoma, ganglioneuroma, gangliocytoma or ganglioneuroblastoma.
  2. Your child’s diagnosis was made at a Children’s Oncology Group (COG)-affiliated hospital in the US, Puerto Rico or Canada. Click here to view COG hospitals by state or country.
  3. Your child’s diagnosis was made on or after December 24, 2007.
  4. At the time of diagnosis, your child was under 6 years of age.
  5. You (the parent/guardian) understand/speak either English or Spanish.
  6. You (the parent/guardian) are 18 years of age or older.

In addition, eligibility also requires that:

  • Your child was registered with the Childhood Cancer Research Network (CCRN) through the Children’s Oncology Group (COG) AND, during that registration process, you or another parent/guardian consented to be contacted for non-therapeutic studies. NENA is not allowed to include families who did not provide this permission.
  • The biological mother be available and willing to participate either with her child who is living or on behalf of her child who is deceased. Due to the fact that NENA focuses on exposures during pregnancy, as well as genetic factors that may be related to the development of the disease, biologically linked pairs of mothers and children are essential for this research study. Biological fathers are also encouraged to participate, however, their availability and willingness to be part of the study is not an eligibility requirement.

If you have reviewed the information above and believe you are eligible to participate in the NENA Study, please contact us via email or phone. We are happy to answer any questions you have about study participation.

See the NENA Frequently Asked Questions tab on this page.

 

 

What is the NENA Study?

Why is this research being done?

Who is paying for this research?

What is the difference between this study and a clinical trial?

What is a gene? What is DNA? Why are they important to research?

I received information in the mail from the NENA Study. How did you get my name and contact information?

My child was not diagnosed with neuroblastoma. Why am I receiving this information and am I still eligible to participate in the NENA Study?

Are we required to participate in this research study?

What does participation involve? How long will it take?

Will the saliva collection collection cause any pain or discomfort for parents or children?

Will participating in NENA cost me anything?

Will I have to travel anywhere or will anyone come to my home?

What will we get for participating?

What will happen to the information and saliva that participants provide?

Since DNA is being analyzed, what security measures will be taken in order to protect the identities of participants?

How can participants request that a saliva sample be destroyed?

How will participants’ privacy be protected?

Will I receive results from this study if I participate?

What if my child has passed away?

I am not a biological parent. Can I still participate?

I do not live with my child’s other biological parent. Can the other parent still participate?

I am not in contact with my child’s other biological parent. Can the other parent still participate?

What if I know now that I definitely DO want to participate?

I may beinterested in participating, but this is a bad time for me and/or my family. What should I do?

What if I am having trouble making a decision about participating?

What if I know now that I definitely DO NOT want to participate?

I did not receive any information in the mail or any phone calls from the NENA Study. However, I found this information on your website and am interested in participating. How can I take part in the NENA Study?

What is the NENA Study?

The Neuroblastoma Epidemiology in North America (NENA) Study, led by Dr. Andrew F. Olshan and funded by the National Cancer Institute at the National Institutes of Health, is a research study which investigates different factors that may play a role in the development of neuroblastoma in young children. Approximately 600 biological mothers and 500 biological fathers of children with neuroblastoma will participate in this research study over a period of 5 years.

If you received a letter from our study office, it is due to the fact that your child is registered with the If you received a letter from our study office, it is due to the fact that your child is registered with the Childhood Cancer Research Network (CCRN) through the Children’s Oncology Group (COG). During that registration process, you or another guardian indicated willingness to be contacted for non-therapeutic studies. NENA is a non-therapeutic study approved by COG, who provided us with your contact information because your child was diagnosed with neuroblastoma. Therefore, you and your child may be eligible to participate in NENA. If your child is now deceased, NENA can still benefit from your participation.
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Why is this research being done?

The goal of this research is to understand how genes might affect young children’s chances of developing neuroblastoma. To do this, we would like to compare the genes of children with neuroblastoma to the genes of their parents. Mothers in the study also provide information about their health, diet, and family history of cancer, as well as which vitamins and medications they may have taken during pregnancy. Our researchers can then analyze all of this information in various ways to learn about different factors in the development of neuroblastoma.
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Who is paying for this research?

This research is funded by the National Cancer Institute at the National Institutes of Health. The principal investigator at the University of North Carolina at Chapel Hill is Dr. Andrew F. Olshan.
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What is the difference between this study and a clinical trial?

Unlike a clinical trial, we will not ask participating children or adults to take drugs or medicine of any kind, and we will not treat children’s neuroblastoma. Joining this study is voluntary and separate from a child’s treatment. Families do not have to be involved with research in order for their children to receive medical treatment. A family’s decision about participating in NENA will not change the relationship with the child’s doctor(s), the treatment they recommend, or the medical care the child receives. Families may refuse to join or may withdraw consent to be in the study, for any reason and at any time, without penalty.
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What is a gene? What is DNA? Why are they important to research?

A gene is the basic unit of heredity in a living organism. All living things depend on genes. Genes hold the information to build and maintain cells and to pass genetic traits on to children.

DNA is the genetic material in a person’s cells that makes each individual unique. There are thousands of genes made up of DNA in each cell. For our study, we ask participants to provide saliva samples that our lab can extract DNA from. By studying the DNA, scientists can discover the genes that might be involved in the development of neuroblastoma.

Just as each person has a unique fingerprint, we each have a unique set of genes that may be studied by examining a DNA sample. All human beings are 99.9% identical in their genetic makeup. Differences in the remaining 0.1% hold important clues about the causes of diseases. By studying samples of these genes in a large group of study participants, researchers can help society by identifying who might be at increased genetic risk for certain diseases. This can lead to better screening and treatment options in the future.
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I received information in the mail from the NENA Study. How did you get my name and contact information?

NENA is a non-therapeutic study that is approved by the Children’s Oncology Group (COG). You are being asked to be in the study because your child is registered with the Childhood Cancer Research Network (CCRN) through the Children’s Oncology Group (COG). During that registration process, you or another guardian indicated willingness to be contacted for non-therapeutic studies. COG provided us with your contact information because your child was diagnosed with neuroblastoma. Therefore, you and your child may be eligible for participation in our study.
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My child was not diagnosed with neuroblastoma. Why am I receiving this information and am I still eligible to participate in the NENA Study?

In order to learn more about neuroblastoma, the NENA study also includes families of children diagnosed with ganglioneuroma, gangliocytoma and ganglioneuroblastoma. These conditions fall along the benign end of the neuroblastoma disease spectrum. There may be similarities to the way all of these diseases develop in terms of risk factors. For this reason, families and children diagnosed with these conditions have a unique opportunity to help advance scientific knowledge about these diseases, and to help other families, by participating in the NENA Study.
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Are we required to participate in this research study?

No, joining the study is voluntary and separate from your child’s treatment. You do not have to be involved with research in order for you or your child to receive medical treatment. You may refuse to join, or you may withdraw your consent to be in the study, for any reason and at any time, without penalty.
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What does participation involve? How long will it take?

Adults will be asked to review and sign a consent form that gives our research study permission to analyze the information provided on the Mother’s Questionnaire (biological mothers only) as well the saliva sample you send to our lab. Adults will also be asked to review and sign a parental consent form that gives our study permission to analyze the child’s saliva or tissue sample in our lab. If you have any concerns about providing consent for yourself or your child, please contact the NENA study office as soon as possible. Trained study staff can answer your questions about NENA and explain the consent forms in more detail.

BIOLOGICAL MOTHERS will be asked to complete a paper/pen Mother’s Questionnaire that asks about their health, pregnancy and medical history, family health history, their intake of certain foods, drinks, and vitamins as well as their child’s early feeding habits. Biological mothers will also be asked to collect their own saliva sample to send to our study lab. Both of these activities can be completed at home. The questionnaire will take approximately one hour to complete, and collecting their own saliva sample will take approximately 20 minutes. Therefore, biological mothers should expect to devote a total of 60 to 90 minutes for participation in the study.

BIOLOGICAL FATHERS will be asked to collect their own saliva sample to send to our study lab. These kits are the same type as the mother’s kits, so biological fathers should expect to devote about 20 minutes for their own participation in the study.

If your CHILD is living, you will be asked to collect a saliva sample from him or her using a kit with small, soft sponges that are designed especially for use with young children. While this procedure should take about 15 minutes, this time may be more or less depending on your child’s age and mood.

If your CHILD is deceased, you will be asked to sign and return a parental consent form. This form allows NENA to obtain and analyze part of a tissue sample if your family previously agreed to have your child’s tissue sample collected and stored by COG.
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Will the saliva collection collection cause any pain or discomfort for parents or children?

There is a slight chance that the collection process may slightly irritate the mouth and/or inner cheek of parents and children who provide saliva samples. However, the child collection kit was specifically designed for use with very young children, so we expect the risk of discomfort to be quite minimal and usually the result of not being accustomed to having the inside of the cheek swabbed with a sponge. If adults or children experience any discomfort, it should stop as soon as the collection process ends. Other parents and young children have used these kits as part of our study and found them to be quite tolerable. Please see the ORAgene-500 Adult Tube Collection Kit Instructions and FAQs which explains the collection process for adults and the ORAgene-250 Child Collection Kit Instructions and FAQswhich explains the collection process for children and provides some helpful tips on timing the collection process.
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Will participating in NENA cost me anything?

No. There is no financial cost for children or biological parents to be in this research study.
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Will I have to travel anywhere or will anyone come to my home?

No. All steps of NENA participation can be done by you in your own home and via mail. In addition, study staff at the University of North Carolina-Chapel Hill will be available by phone and email to assist you.
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What will we get for participating?

Biological mothers who complete and return the questionnaire will receive $40. Biological mothers and fathers who collect and return their own saliva samples will receive $10 each. You will also receive one payment of $10 for collecting and returning your child’s saliva sample. If your child is deceased, you will receive $10 if you sign and return the parental consent form. The maximum a family can receive is $70.
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What will happen to the information and saliva that participants provide?

Once individuals and/or families agree to participate in NENA, each family member will be assigned a unique six-digit NENA Study ID number. This number will not be generated from a name, a date of birth, an address, or any other identifying information. When we receive a completed Mother’s Questionnaire, it is scanned by a machine, and the data obtained are deidentified and only retain the unique NENA Study ID number. Data from all of the mothers in the NENA Study are entered into a confidential database that can only be accessed by study staff. At the end of the study, the questionnaire data will be analyzed to determine whether factors related to general health, pregnancy and medical history, family cancer history, intake of certain foods, drinks, and vitamins, and a child’s early feeding habits might influence the development of neuroblastoma in children.

All saliva and tissue samples will be identified only by a unique NENA Study ID number as well. These samples will be processed in our lab where DNA will be extracted. Our research team will then compare the genes of children with neuroblastoma to the genes of their biological parents in order to better understand how heredity might affect the development of this disease.
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Since DNA is being analyzed, what security measures will be taken in order to protect the identities of participants?

Once they are sent for analysis, saliva and tissue samples will not contain any identifying information, such as a name, a date of birth, or an address. Samples will only contain a label on which the participant’s unique NENA Study ID number appears. Upon arrival at the lab, saliva kits will be provided with another layer of IDs that is separate from the unique NENA Study ID number. Therefore, no lab personnel will be able to link saliva and tissue samples with any identifiable information. Although some samples may eventually be looked at by another lab, that lab would only receive deidentified samples, and no linkages to identifiable data will be possible. The specimens will be kept in our NENA lab indefinitely unless the participant requests that it be destroyed.
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How can participants request that a saliva sample be destroyed?

Participants can request that their saliva sample be destroyed at any time until 2014 by contacting Dr. Andrew Olshan, the Principal Investigator of the NENA Study. After 2014, we will remove the participant’s name from our files, and we will not be able to identify the participant’s saliva sample. The saliva samples provided for this study will be stored long-term unless a participant requests that it be destroyed before then.
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How will participants’ privacy be protected?

Contact information for eligible families that is received by NENA from the CCRN is maintained on a secure network in password-protected files with extremely limited access. Our approved staff use this information in order to send materials about the NENA Study to eligible families. Only approved study programmers, the Project Director and research assistants will be given the passwords and training to link study IDs with identifiable information. In addition, all study personnel with access to linking information have completed human subjects training at the University of North Carolina and were required to sign an additional NENA study confidentiality agreement form.

The NENA research team takes every measure possible to ensure privacy for families while they participate in our study. Participants are identified by a unique ID only, which appear as a nonsensical group of numbers to anyone except approved NENA staff. Questionnaires, saliva samples, and consent forms are labeled with this identification system which prevents data and/or specimens from being linked to any individual or family. Phone conversations made to participants are conducted in private offices with closed doors, and mailings that participants receive do not identify the focus of the study. NENA is in full compliance with the University of North Carolina-Chapel Hill Institutional Review Board which protects the rights of participants in research studies. If participants have questions or concerns about their rights as a research subject, or if they would like to obtain information or offer input, they may contact the Institutional Review Board at 919-966-3113 or by sending an email to IRB_subjects@unc.edu. Further information about participant privacy is included in the NENA Study consent forms which all potential participants receive and review before agreeing to be part of the study. Participants in NENA will not be identified in any report or publication about this research study.
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Will I receive results from this study if I participate?

WE WILL NOT PROVIDE INDIVIDUAL RESULTS FROM THE MOTHER’S QUESTIONNAIRE OR FROM LABORATORY ANALYSIS INVOLVING THE BIOLOGICAL MOTHER’S SALIVA SPECIMEN, THE BIOLOGICAL FATHER’S SALIVA SPECIMEN, OR THE CHILD’S SALIVA OR BANKED TISSUE SPECIMEN. Our research is not designed to assess each person’s results or to inform each family about hereditary risks. This means that we cannot tell participants what their lab results are, and we cannot advise families about their risk of passing genetic susceptibilities for neuroblastoma on to future children. We will also not disclose any genetic information regarding either maternity or paternity of the child. In other words, if our lab results show that a participating parent is not the biological parent of a child enrolled in the study, we will not notify the family about these results. After the study has been completed, we expect to compile study-wide findings and will share those with participants when they are available.
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What if my child has passed away?

If your child is deceased, you may still participate on his or her behalf by providing parental consent for our study to access banked tissue that has already been collected and stored through COG. Our study can learn more about neuroblastoma by analyzing this tissue at our lab.
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I am not a biological parent. Can I still participate?

Due to the fact that this study will be examining genetic relationships and events occurring during pregnancy, adults who provide saliva samples and mothers who complete the questionnaire must be the biological parents of the child with neuroblastoma. However, if you are the guardian of a child diagnosed with neuroblastoma, and neither biological parent has custody, we may contact you about providing parental consent for your child.
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I do not live with my child’s other biological parent. Can the other parent still participate?

Yes. Because this study explores the role genetics play in the development of neuroblastoma, it is very helpful for us to include both biological parents, regardless of where they live. If you are willing to provide contact information for your child’s other biological parent, our study will invite him/her to participate. You do not need to have any contact with your child’s other parent if you do not wish to. NE NA staff can explain the study and provide materials separately to biological parents as needed. In addition, we encourage you to participate even if your child’s other biological parent does not wish to be involved in the study.
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I am not in contact with my child’s other biological parent. Can the other parent still participate?

Yes. Both biological parents are encouraged to participate in the research study. If you have contact information for the other biological parent and are willing to provide it to our study team, we will invite him/her to participate. You do not need to have any contact with your child’s other parent about NENA. Our staff can explain the study to him/her and provide materials as needed. In addition, we encourage you to participate even if your child’s other biological parent does not wish to be involved in the study.
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What if I know now that I definitely DO want to participate?

We are very appreciative of your interest in our study. If you know now that you DO want to participate, please fill out and return the Interest Form that you received. Returning this form does NOT mean you are enrolled in the study. If you have not received an Interest Form, please contact the study office so that we can further assist you.

Once we receive your completed Interest Form, we will correspond with you further based on the information you provide. If you have indicated that you would like to participate in NENA, we will send you a package containing consent forms as well as the appropriate study materials. Once the package arrives, please read the consent forms carefully and call our study office if you have any questions about them. We are here to help you understand all aspects of the study before deciding whether or not to participate.
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I may be interested in participating, but this is a bad time for me and/or my family. What should I do?

We understand that our mailing may have arrived at a difficult time for you and your family, either due to your child’s treatment, family needs, or other challenging situations. If you think you might be interested in our study at a later date, but are not ready to decide at this time, please indicate this on the Interest Form that you received. You may then use the prepaid manila envelope that you received to return the Interest Form to the University of North Carolina. Our research team will respect your need for more time and then re-contact you after the date that you specify on the Interest Form. If you have not received an Interest Form, please contact the study office so that we can further assist you.
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What if I am having trouble making a decision about participating?

We want you to have all of the information you need in order to make an informed decision about participation. If you are not sure right now, please indicate this on the Interest Form that you received. You may then use the prepaid manila envelope that you received to return the Interest Form to the University of North Carolina. Someone from our study team will contact you to answer any questions you have and to discuss the study in more detail. If you have not received an Interest Form, please contact the study office so that we can further assist you.
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What if I know now that I definitely DO NOT want to participate?

Please fill out the small blue sheet that you received in your mailing and use the prepaid manila envelope you received to return it to the University of North Carolina. We respect your right to decline participation for any reason, and we will not contact you again about the NENA Study. If you have not received an Interest Form, please contact the study office so that we can further assist you. You may also call the study office and indicate that you do not want to be contacted about NENA.
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I did not receive any information in the mail or any phone calls from the NENA Study. However, I found this information on your website and am interested in participating. How can I take part in the NENA Study?

If you have not been contacted by our study, either through mail or telephone, you are most likely not eligible to participate. In order to be eligible for participation in NENA, families must have a child who was diagnosed with neuroblastoma at a COG affiliated hospital on or after December 24, 2007. In addition, the child MUST have been diagnosed before the age of 6, and he/she must be enrolled in the Childhood Cancer Research Network (CCRN). During enrollment in the CCRN, parents/guardians must also consent to being contacted for other studies. If you think you meet these criteria and have not been approached by NENA, please email or call our study office for assistance. If you have not been enrolled in the CCRN but would like to be, please contact your treating institution to inquire about enrollment.
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Scientific publications, relevant presentations, and new articles related to the NENA Study – link.

 

What is Epidemiology?

Epidemiology is the science of understanding why some people get certain diseases and others don’t. Epidemiology concentrates on populations, whereas clinical medicine concentrates on the individual. It is believed that diseases are not randomly distributed throughout the population, but rather that different groups of people have a higher risk of illness based on their environment, health habits, and genetics.

Epidemiologists are often referred to as medical detectives since they work together with doctors, laboratory scientists, and others to try to piece together clues that are not always apparent, but which may point to the causes of a disease.

What is Cancer Epidemiology?

Cancer epidemiology focuses on the causes of cancer in the population. Since cancer is believed to occur over many months or even years, understanding its causes can be complex. Often times, the cancer epidemiologist uses what is called a ‘case-control’ approach to study the disease. In this case, people with and without a particular cancer are identified. Interviews are usually conducted and typically focus on individual health histories and habits. Sometimes medical records are also studied to investigate areas of interest that people often have difficulty remembering. The groups with and without cancer are then compared and researchers look for patterns or trends. However, research conducted by the NENA Study includes cases only. There are no participants acting as controls for this research.

Helpful Links

National Cancer Institute of the United States
National Institutes of Health – Epidemiology Branch
National Cancer Institute – Division of Cancer Epidemiology and Genetics
CureSearch
Canadian Cancer Society / National Cancer Institute of Canada
Blood and Marrow Transplant (BMT) Information Network
National Children’s Cancer Society