The American Cancer Society lists the most common cancers in children:
What are the most common types of childhood cancers?
The types of cancers that occur most often in children are different from those seen in adults. The most common cancers of children are:
Other types of cancers are rare in children, but they do happen sometimes. In very rare cases, children may even develop cancers that are much more common in adults…. http://www.cancer.org/cancer/cancerinchildren/detailedguide/cancer-in-children-types-of-childhood-cancers
Increasingly, scientists are discovering many diseases occur because of a genetic predisposition.
Genetics Home Reference answers: What does it mean to have a genetic predisposition to a disease?
A genetic predisposition (sometimes also called genetic susceptibility) is an increased likelihood of developing a particular disease based on a person’s genetic makeup. A genetic predisposition results from specific genetic variations that are often inherited from a parent. These genetic changes contribute to the development of a disease but do not directly cause it. Some people with a predisposing genetic variation will never get the disease while others will, even within the same family.
Genetic variations can have large or small effects on the likelihood of developing a particular disease. For example, certain mutations in the BRCA1 or BRCA2 genes greatly increase a person’s risk of developing breast cancer and ovarian cancer. Variations in other genes, such as BARD1 and BRIP1, also increase breast cancer risk, but the contribution of these genetic changes to a person’s overall risk appears to be much smaller….
In people with a genetic predisposition, the risk of disease can depend on multiple factors in addition to an identified genetic change. These include other genetic factors (sometimes called modifiers) as well as lifestyle and environmental factors. Diseases that are caused by a combination of factors are described as multifactorial. Although a person’s genetic makeup cannot be altered, some lifestyle and environmental modifications (such as having more frequent disease screenings and maintaining a healthy weight) may be able to reduce disease risk in people with a genetic predisposition. http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/predisposition
St. Jude Children’s Research Hospital reported that many pediatric cancers are the result of a genetic predisposition.
Science Daily reported in More than 8 percent of children with cancer have genetic predisposition:
The most detailed analysis yet of the role germline mutations in genes associated with cancer predisposition play in the development of childhood cancer suggests that comprehensive genomic screening may be warranted on all pediatric cancer patients, not just those with a family history of cancer. The study from the St. Jude Children’s Research Hospital — Washington University Pediatric Cancer Genome Project appears in the November 19 edition of the New England Journal of Medicine.
Ultimately, researchers anticipate that systematic monitoring of patients and family members who have germline mutations in cancer predisposition genes will allow the detection of cancers at their earliest and most curable stage, thereby improving the outcomes for these children and family members.
Researchers conducted next-generation DNA sequencing of both the tumor and normal tissues from 1,120 pediatric cancer patients and found that 8.5 percent of patients had pathogenic or likely pathogenic mutations of genes within their normal tissue that increase their risk of developing cancer. Prior to this study, the presence of such germline mutations in pediatric cancer patients was thought to be extremely rare and restricted to children in families with strong histories of cancer. This study revealed that more than half of the children with germline mutations lacked any family history of cancer.
“This paper marks an important turning point in our understanding of pediatric cancer risk and will likely change how patients are evaluated,” said corresponding author James R. Downing, M.D., St. Jude president and chief executive officer. “For many pediatric cancer patients, comprehensive next-generation DNA sequencing of both their tumor and normal tissue may provide valuable information that will not only influence their clinical management but also lead to genetic counseling and testing of their parents and siblings who may be at risk and would benefit from ongoing surveillance….” http://www.sciencedaily.com/releases/2015/11/151118181247.htm
Citation:
More than 8 percent of children with cancer have genetic predisposition, new study suggests
Date:
November 18, 2015
Source:
St. Jude Children’s Research Hospital
Summary:
The most detailed analysis yet of the role germline mutations in genes associated with cancer predisposition play in the development of childhood cancer suggests that comprehensive genomic screening may be warranted on all pediatric cancer patients, not just those with a family history of cancer.
Journal Reference:
-
Zhang et al. Germline Mutations in Predisposition Genes in Pediatric Cancer. New England Journal of Medicine., Nov. 18, 2015 DOI: 10.1056/NEJMoa1508054
Here is the press release from St. Jude:
New study suggests more than 8 percent of children with cancer have genetic predisposition
St. Jude Children’s Research Hospital-Washington University Pediatric Cancer Genome Project completes the most comprehensive analysis yet of the role genes associated with cancer predisposition play in childhood cancer
Memphis, Tennessee, November 18, 2015
A landmark study uncovers important findings about genetic cancer risk and kids. Learn how St. Jude is using this information to help kids and their families.The most detailed analysis yet of the role germline mutations in genes associated with cancer predisposition play in the development of childhood cancer suggests that comprehensive genomic screening may be warranted on all pediatric cancer patients, not just those with a family history of cancer. The study from the St. Jude Children’s Research Hospital – Washington University Pediatric Cancer Genome Project appears in the November 19 edition of the New England Journal of Medicine.
Ultimately, researchers anticipate that systematic monitoring of patients and family members who have germline mutations in cancer predisposition genes will allow the detection of cancers at their earliest and most curable stage, thereby improving the outcomes for these children and family members.
Researchers conducted next-generation DNA sequencing of both the tumor and normal tissues from 1,120 pediatric cancer patients and found that 8.5 percent of patients had pathogenic or likely pathogenic mutations of genes within their normal tissue that increase their risk of developing cancer. Prior to this study, the presence of such germline mutations in pediatric cancer patients was thought to be extremely rare and restricted to children in families with strong histories of cancer. This study revealed that more than half of the children with germline mutations lacked any family history of cancer.
“This paper marks an important turning point in our understanding of pediatric cancer risk and will likely change how patients are evaluated,” said corresponding author James R. Downing, M.D., St. Jude president and chief executive officer. “For many pediatric cancer patients, comprehensive next-generation DNA sequencing of both their tumor and normal tissue may provide valuable information that will not only influence their clinical management but also lead to genetic counseling and testing of their parents and siblings who may be at risk and would benefit from ongoing surveillance.”
“The frequency of 8.5 percent represents our current estimate of the number of pediatric patients with a hereditary cancer predisposition,” Downing added. “This number will likely increase as we learn more about mutations in this class of genes in young cancer patients.” To accomplish the latter, St. Jude has initiated a new clinical research study, Genomes for Kids (G4K), which incorporates an unparalleled level of next-generation sequencing into the medical workup of every eligible pediatric cancer patient who enters the hospital for treatment.
Any child found to have a germline mutation in a cancer predisposition gene will be referred to the new St. Jude Hereditary Cancer Predisposition Clinic, which evaluates and cares for children who are at increased genetic risk for cancer. The clinic is staffed by a team of doctors, nurses and genetic counselors who work with families to determine if a child’s cancer might be inherited. The staff then collaborates with other St. Jude doctors and researchers to find new and better ways to help families with an elevated cancer risk. This new clinic is one of only a few programs in the world focused on evaluating and managing children and families with known or suspected cancer predisposition.
St. Jude patient Gunner and Kim Nichols, M.D., director of the St. Jude Hereditary Cancer Predisposition Clinic
“Our study in The New England Journal of Medicine lays the groundwork to understand the spectrum of cancers and age-specific cancer risks associated with germline mutations in predisposition genes and how best to monitor at-risk patients and families,” said co-author Kim Nichols, M.D., a member of the St. Jude Department of Oncology and director of the St. Jude Hereditary Cancer Predisposition Clinic.
Co-author Richard K. Wilson, Ph.D., director of the McDonnell Genome Institute at Washington University School of Medicine in St. Louis, added: “We’ve suspected for some time that many pediatric cancers could be traced to an inherited genetic predisposition. Now, using genome sequencing, we can see the contribution of germline mutations to pediatric cancer risk. Our results explain why children, who have not lived long enough to accumulate a critical number of cancer-causing mutations can still develop cancer.”
About the Study and Genetic Sequencing
The human genome is encoded in the DNA that carries the instructions required to assemble and sustain life. Whole-genome sequencing involves determining the exact order of the 3 billion nucleotides that make up human DNA. Whole-exome sequencing involves sequencing the 1 to 2 percent of the human genome that carries the approximately 20,000 human genes.
This study involved sequencing the whole genome, whole exome or both of patients enrolled in the Pediatric Cancer Genome Project to check for germline mutations in 565 genes associated with cancer. In-depth data analysis was done on 60 of these genes that are associated with autosomal dominant hereditary cancer predisposition syndromes. Mutations in these genes are known to increase cancer risk when one of the two copies of the gene is altered.
In this study, 95 patients, or 8.5 percent, had germline mutations in 21 of the 60 genes. Investigators checked whole-exome sequencing data of a comparison group without cancer and found that only 1.1 percent of 966 adults enrolled in the 1000 Genomes Project, an international collaboration to map human genetic variation, had alterations in the same genes.
The genes selected for detailed analysis were chosen based on a review of available cancer and genetic databases, the medical literature and other information. “Finding genomic variants is relatively easy compared to assessing their cancer-causing potential,” said co-first author Jinghui Zhang, Ph.D., chair of the St. Jude Department of Computational Biology. “The system we developed to create the database for this study provides a template for assessing the pathogenic significance of alterations going forward.”
In this study, the frequency of germline mutations in cancer predisposition genes varied by the type of cancer the child had. The highest frequency, 16.7 percent, was found in children with non-central nervous system (CNS) solid tumors, followed by CNS tumors, 9 percent, and leukemia, 4.4 percent.
The most commonly mutated genes in the affected patients were TP53, APC, BRCA2, NF1, PMS2 and RB1. Many of these genes have been previously associated with rare families with multiple children who develop cancer. An unexpected finding was the identification of mutations in the breast and ovarian cancer genes BRCA1 and BRCA2 in a number of the pediatric cancer patients. These genes are not currently included in pediatric cancer genetic screening. The prevalence of mutations in these genes in this pediatric cancer cohort suggests that the role of these genes in pediatric cancer needs to be further studied. “Another surprising finding to emerge from this study was the prevalence of germline mutations in six patients with Ewing sarcoma, a cancer of the bone and soft tissue that was not previously thought to be part of any cancer predisposition syndrome,” Nichols said.
Read the full text of the article:
Germline mutations in predisposition genes in pediatric cancer.
N Engl J Med, Nov 18, 2015. Epub ahead of print. doi:10.1056//NEJMoa1508054
View Media ToolkitThe other co-first authors are Gang Wu, Ph.D., of St. Jude, and Michael Walsh, M.D., formerly of St. Jude and now of Memorial Sloan Kettering Cancer Center, New York. The other authors are Michael Edmonson, Tanja Gruber, John Easton, Dale Hedges, Xiaotu Ma, Xin Zhou, Donald Yergeau, Mark Wilkinson, Bhavin Vadodaria, Xiang Chen, Rose McGee, Stacy Hines-Dowell, Regina Nuccio, Emily Quinn, Sheila Shurtleff, Michael Rusch, Aman Patel, Jared Becksfort, Shuoguo Wang, Amar Gajjar, David Ellison, Alberto Pappo and Ching-Hon Pui, all of St. Jude; Meaghann Weaver, formerly of St. Jude; and Li Ding and Elaine Mardis, both of the McDonnell Genome Institute, Washington University, St. Louis.
The research was funded in part by the Pediatric Cancer Genome Project, including Kay Jewelers, a lead sponsor; a grant (CA021765) from the National Cancer Institute at the National Institutes of Health; and ALSAC.
https://www.stjude.org/media-resources/news-releases/2015-medicine-science-news/new-study-suggests-more-than-8-percent-of-children-with-cancer-have-genetic-predisposition.html
Many couples may want to seek genetic counseling before attempting parenthood.
The Centers for Disease Control and Prevention have excellent information about genetic counseling:
In genetic counseling, specially-trained professionals help people learn about genetic conditions, find out their chances of being affected by or having a child or other family member with a genetic condition, and make informed decisions about testing and treatment.
Reasons for Genetic Counseling
There are many reasons that people go for genetic counseling, such as:
- A family history of a genetic condition
- To learn about genetic screening for diseases that are more common in certain ethnic groups (e.g., sickle cell disease in African Americans and Tay-Sachs disease in Ashkenazi Jews)
- To discuss abnormal results from tests during pregnancy (such as a blood test, ultrasound, chorionic villus sampling (CVS), or amniocentesis)
- To learn about the higher chance for certain types of genetic conditions (such as Down syndrome) in the baby if mother-to-be is 35 years of age or more, or is concerned at any age about her chances of having a child with a genetic condition
- To learn about the effects of being exposed to x-rays, chemicals, illness, or prescribed or illicit drugs while pregnant
- A woman has had several miscarriages or infant deaths
- Trouble getting pregnant (infertility)
- A genetic condition or birth defect occurred in a previous pregnancy
- A child has birth defects, disabilities, or conditions found by newborn screening
- To find out if there is a genetic cause for developmental delays or health problems
- Steps to get ready for a healthy pregnancy and baby (such as screening for genetic conditions)
About Genetics Professionals
Clinical geneticists and genetic counselors often work together as part of a health care team. They diagnose and care for people with genetic conditions and give information and support to people with genetic conditions and their families…. http://www.cdc.gov/ncbddd/genetics/genetic_counseling.html
It is important that competent medical professionals are consulted to not only diagnose, but to interpret and explain any genetic probability.
Resources:
Childhood Cancers http://www.cancer.gov/types/childhood-cancers
Cancer in Children http://www.cancer.org/cancer/cancerinchildren/
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