Understanding Genetic Predisposition to Cancer

Understanding Genetic Predisposition to Cancer 1024 683 Susan Colasce, MD and Elizabeth Varga

When should families who have children with cancer be concerned about inherited cancer predisposition?

One of the most common questions parents ask when their child is diagnosed with cancer is, “Does this put my other children at higher risk for developing cancer as well?” Most of the time, the answer to this question is “no.” However, 5-15 percent of childhood cancers are associated with a genetic predisposition to cancer.

Families typically seek testing for genetic predisposition to cancer for one of two reasons: For families already coping with the difficulties of a new cancer diagnosis in their child, the idea that their other children could be at risk of having cancer is a terrifying one. Other families may have had multiple adults with cancer and are wondering if it is just bad luck or if cancer really does “run in the family.”

While the majority of cancers are not a sign of a possible genetic predisposition to cancer, there are some diagnoses and patterns worthy of further investigation. Oncologists and genetic counselors can take a pedigree (family tree) to identify the particular types of cancer that have been diagnosed in one family and the age of development of cancers and, from there, determine if further genetic testing is needed.

For childhood cancers, in the absence of a strong family history of cancer, genetic testing only needs to be done if the child has had more than one type of cancer, or has had a cancer known to be related to genetic variants.

One cancer predisposition syndrome of note is Li-Fraumeni syndrome (LFS), named after two physicians who first described the disorder. LFS is a rare cancer predisposition syndrome with fewer than 1000 families described worldwide. LFS is caused by a change in the gene called TP53. This gene provides the instructions for making the p53 protein, which normally acts to regulate cell division. Because of the important role of p53 in the body, it is often called the “guardian of the genome”.

People with LFS are more likely to develop particular types of cancer, including sarcoma of the soft-tissue or bone. Other associated cancers include breast cancer, leukemia, and cancer of the colon, stomach, pancreas, adrenal cortex and brain. More than half of all cancers in the context of LFS occur before the age of 35. For this reason, special screening and monitoring is recommended for those with LFS to help identify cancer at an early stage.

While genetic testing for LFS is fairly straightforward, in many cases, the specific gene or condition to test for might not be as obvious. It is important for experts in cancer genetics to take a thorough medical and family history and determine if multiple genes should be tested at once. This is done frequently for patients with concerning personal and family histories using a gene panel, in which multiple genes can be tested using one blood or saliva sample.

Prior to genetic testing, thorough counseling should be provided to discuss advantages, disadvantages and limitations of testing, as well as to explore the emotional implications for the family. If testing is pursued, results from genetic testing are usually available in about four to six weeks.

Once the results are in, a physician and/or a licensed genetic counselor will go over the results with the family. They will discuss screening and management options, including testing for other family members. Management guidelines will vary depending on individual genetics, age and cancer history. Because of these complexities, specialists in cancer and genetics are the best resources for developing a personalized management plan.

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About the author

Susan Colace, MD, is the Co-Director of the Program for Personalized Medicine and Pharmacogenomics in Pediatric Hematology/Oncology/Blood and Marrow Transplant at Nationwide Children's Hospital and an Assistant Professor at The Ohio State University College of Medicine. Dr. Colace received her medical degree from Wake Forest University School of Medicine and completed her residency at Children's Hospital of Alabama. Dr. Colace completed her fellowship training at Monroe Carrell Jr. Children's Hospital and Vanderbilt University Medical Center.

She is board-certified in general pediatrics, pediatric hematology/oncology and clinical pharmacology. Her research interests include pharmacogenomics, cancer genetics, and chemotherapy toxicities. Clinically, she sees primarily oncology patients with a focus on leukemia and cancer predisposition syndromes.

Elizabeth Varga, MS, CGC, is the director of Clinical Genomics Research and Development in the Steve and Cindy Rasmussen Institute for Genomic Medicine at Nationwide Children’s Hospital and is a licensed genetic counselor and adjunct assistant professor of Pediatrics at The Ohio State University. She oversees development and implementation of genomic research protocols into various services lines across Nationwide Children’s and manages the Clinical Genomics research team comprised of genetic counselors, research coordinators and data/regulatory staff.

Elizabeth has almost 20 years of clinical experience as a genetic counselor, with specific expertise related to the genomics of pediatric hematologic, oncologic and immunologic disorders. She has served on the Board of Directors for the National Society of Genetic Counselors and was a founding Board member of the National Blood Clot Alliance.