Li-Fraumeni syndrome linked to more cancers than we thought

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

Li-Fraumeni syndrome is a rare but devastating condition that occurs when people have a fault in the gene TP53; this fault (a pathogenic variant) is known to put them at extremely high risk of developing multiple cancers during their lifetime, including breast cancer, osteosarcoma (bone cancer) and cancer of the soft tissue and brain. The new research, published in the journal JCO Precision Oncology, shows that this risk actually extends to cancers not traditionally associated with the syndrome — including leukaemia, colorectal, lung and gastric cancers, with higher risks in females compared to males.

The study is based on data from 146 TP53-positive families in Australia, Spain and the USA, comprising 4028 individuals. 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.

“The study calculated specific cancer risks by age and sex for each cancer and all cancers combined,” said Fortuno, who is based at QIMR Berghofer. “Importantly, it identified increased lifetime risks for additional cancers outside the core Li-Fraumeni syndrome cancers.

“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,” Spurdle said. “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.”

Clinical geneticist Professor Paul James, lead collaborator from the Peter MacCallum Cancer Centre, 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,” he said. “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.”

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