The Li-Fraumeni Syndrome Association (LFSA), dedicated to furthering research and worldwide awareness of the inherited cancer predisposition disorder, celebrates new findings published in the renowned JAMA Oncology journal with implications to better predict cancer risk. First presented at LFSA’s 5th International Symposium last year, the concept of analyzing tumor patterns and genetic testing criteria can accelerate future research toward the development of more tailored approaches for cancer surveillance.
Li-Fraumeni syndrome (LFS) is an inherited cancer predisposition disorder often associated with early-onset cancers affecting families, with particularly unique risks for children and women:
- Females with LFS have approximately 90% risk of developing cancer in their lifetime due to their markedly increased risk of breast cancer
- Approximately 40% of children with LFS will develop at least one cancer by the age of 18
- Those with LFS have an approximately 50% chance of developing cancer by age 40, and up to 90% by age 60
- Each child born to a parent with LFS has a 50% chance of inheriting the mutation
First recognized in 1969 by Dr. Frederick Li and Dr. Joseph Fraumeni through their study of childhood cancer and cancer-prone families, LFS was later found to be caused by inherited defects of the TP53 gene, which serves as a tumor suppressor and is among the most widely studied human genes. LFS research contributes strongly to cancer research as most cancers in the general population involve TP53 gene malfunctions.
“These new findings lead the way for LFS patients and providers to make more informed decisions about surveillance and treatment based on our personal risk factors, with potential to improve prognosis,” said Jenn Perry, LFSA co-founder and president.
The findings published in JAMA Oncology resulted from a collaboration of an international team of researchers supported by LFSA and initiated by Professor Christian Peter Kratz, Hannover Medical School in Hannover, Germany.
“With the increasing use of TP53 sequencing over the last three decades, it became clear that the disease spectrum is broader than originally described. The new classification is an important step toward defining the factors that predict the unique cancer risk in individuals with LFS,” said Kratz.
Using the International Agency for Research on Cancer database, the research team analyzed data from 3,034 patients with a hereditary TP53 variant and identified differences between variants in patients with severe disease compared to those with milder courses.
“This new classification recognizes that LFS represents a spectrum of clinical presentations rather than a ‘one-size-fits-all’ syndrome. We anticipate that, armed with this knowledge, the LFS research community will be able to work toward refining predictions of individual cancer risk and tumor surveillance protocols will be modified to the unique genetic and clinical features of the patient,” said David Malkin, Hospital for Sick Children (SickKids) in Toronto, Canada, and senior author.
Malkin and Kratz were joined by senior author Professor Pierre Hainaut, from the Institute for Advanced Biosciences in Grenoble, France, and researchers from Brazil, England and the United States on the project. It was first discussed in October 2020 at the most recent LFSA sponsored international symposium, where providers, researchers, medical students and people with LFS from around the world have a unique opportunity to collaborate.
The paper honors the memory of Professor Thierry Frébourg, a major contributor to cancer genetic research and LFS Association France chapter chair, who passed away unexpectedly earlier this year.
