New findings could be life-changing for genetic syndrome sufferers

QIMR Berghofer

28 February 2024

An international research team led by QIMR Berghofer and Peter MacCallum Cancer Centre has discovered that people with the hereditary cancer disorder, Li Fraumeni Syndrome, are at greater risk of a much broader spectrum of cancers than previously thought.

Li Fraumeni Syndrome is a rare but devastating condition, which occurs when people have a fault in a gene called TP53. This fault (a pathogenic variant) puts them at extremely high risk of developing multiple cancers during their lifetime.

The new research shows that this risk extends to cancers not traditionally associated with the syndrome, including leukaemia, colorectal, lung and gastric cancers, with higher risks in females compared to males.

QIMR Berghofer researcher and lead author Dr Cristina Fortuno said the findings, which provide accurate estimates of risk by cancer type, age and sex, could help improve early cancer diagnosis and treatment for people with the syndrome.

Lead author Dr Cristina Fortuno and Co-Author Professor Amanda Spurdle

“The study calculated specific cancer risks by age and sex for each cancer and all cancers combined. Importantly, it identified increased lifetime risks for additional cancers outside the core Li Fraumeni Syndrome cancers,” said Dr Fortuno.

“This information is crucial for improving screening and clinical management strategies for carriers of the TP53 gene fault and will help clinicians to detect and manage cancer at an earlier stage.”

Co-author Professor Amanda Spurdle, Group Leader of QIMR Berghofer’s Molecular Cancer Epidemiology Laboratory, said the research substantiates the use of broad surveillance strategies including dedicated brain and whole-body Magnetic Resonance Imaging, but emphasises the need to extend screening methods.

“The findings highlight the critical role of dedicated breast screening for women from a young age. They also raise the question of whether more consideration should be given to offering other targeted risk management approaches such as colonoscopy, prostate cancer screening and risk reducing surgery to prevent ovarian cancer, as standard care for people with Li Fraumeni Syndrome,” said Professor Spurdle.

Lead collaborator from the Peter MacCallum Cancer Centre, clinical geneticist Professor Paul James, highlighted the importance of the findings for families.

“Routine screening and check-ups are essential for people with Li Fraumeni Syndrome, but the ability to calculate which cancers may affect people at various ages could be life-changing. We hope this new knowledge will help enhance the existing management guidelines for people with these gene faults and will encourage more research into this syndrome,” said Professor James.

The study has been published in the online journal JCO Precision Oncology. It assessed data from 146 TP53-positive families in Australia, Spain, and the USA (comprising 4,028 individuals).

It is estimated that one in 10,000 people have Li Fraumeni Syndrome. The “core” cancers most commonly linked to the condition include breast cancer, osteosarcoma (bone cancer), and cancer of the soft tissue and brain.

Dr Fortuno said the research would not have been possible without the support of many families with Li Fraumeni Syndrome, as well as Familial Cancer Clinics and Cancer Foundations and Institutes in Australia, the USA and Spain. The study involved collaboration with analyst Dr Bing-Jian Feng from the Huntsman Cancer Institute, University of Utah.

Funding supporters of this research include the NHMRC (National Health and Medical Research Council), and the National Breast Cancer Foundation, Australia.

The research is available at JCO Precision Oncology with DOI: 10.1200/PO.23.00453.

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