Research study gives insight into genetic causes of cancer

A new research study across Sydney Children’s Hospitals Network is helping clinicians to understand the role of inherited genes play in the development of childhood cancer.

The PREDICT study is being run across the Kids Cancer Centre (KCC) at Sydney Children’s Hospital, Randwick and the Cancer Centre for Children (CCFC) at The Children’s Hospital at Westmead and is using genome sequencing to identify and better understand the genetic variants that can cause inherited cancers.

The program looks at the genes of patients and their parents to screen for variations that identify a predisposition for cancer to develop. If identified, doctors can then screen siblings for these same mutations, allowing for potential early diagnosis and early treatment. 

Professor Tracey O’Brien, Director of KCC, is Co- Principal Investigator of the PREDICT study with Dr Luciano Dalla-Pozza, Head of the CCFC. Professor O’Brien said the study could ultimately help improve outcomes for children and give greater understanding to childhood cancer.

“In some cases, cancer can be caused by abnormal genes being passed along from generation to generation. Family history of cancer is a useful indicator but is not as sophisticated or reliable as looking at the genetic code,” Professor O’Brien said.

“This study builds on the research we have done in the Zero Childhood Cancer Program which showed that 16 per cent of children with the most aggressive forms of cancer also had an inherited cancer predisposition.”

“What the PREDICT study hopes to determine is the proportion of all childhood cancers, not just the aggressive ones, where inherited genetic mutations play a role,” Professor O’Brien said.

Findings of the study may help change treatment protocols and surveillance follow-up for children diagnosed with cancer who are also shown to have a genetic predisposition. This will mean an increased chance of identifying secondary cancers early, which could leave to improved outcomes for these patients.

“The more we know about these genetic factors, the more hope we have that one day we can identify cancer causing genes in some children and ultimately screen and pick up cancers before they cause harm to growing bodies and need aggressive treatments,” Professor O’Brien said.

Life changing benefits for families

Debbie’s son, Yianni, was diagnosed with an aggressive and rare kidney cancer, in 2010 when he was four years old.

During his diagnosis, Yianni underwent genetic testing which revealed that his cancer was caused by a germline mutation in the DICER1 gene. This mutation causes an increased risk of developing tumours, particularly on the lungs, kidneys, ovaries and thyroid gland in the lower neck. 

The discovery led to additional family screening and enabled doctors to pick up the same tumour in Yianni’s twin sister, Patricia, before she began showing symptoms.

This early diagnosis meant that Patricia was able to have her tumour removed through surgery and avoided needing any chemotherapy.

“It is only because of the genetic testing that we were able to find out that Patricia and I also carried the same genetic mutations to the DICER1 gene,” Debbie said.

“We were so lucky because for Patricia it meant that we found her kidney tumour in time. Had we not known, the tumour could have spread further and made her much sicker. She may not have been doing as well as she is today.”

Regular surveillance can mean early detection and better outcomes

Regular surveillance has continued to prove to be incredibly valuable as Patricia has grown up, helping to identify an ovarian tumour in 2019. Thankfully, this was also able to be treated before it had the chance to spread and cause her further health issues. 

Yianni and Patricia are now both doing well and enjoying their teenage years. They will continue to have routine surveillance and check-ups every six months, as will their mum, but the future is bright. 

Dr Bhavna Padhye, who is an Oncologist in CCFC and the clinical lead for the PREDICT study at Westmead, said Yianni and Patricia’s story highlights how beneficial the PREDICT study will be for newly diagnosed patients. 

“Yianni and Patricia were treated before the PRECICT study began but their journey shows us the difference we can make once a genetic mutation has been identified.”

“We have now been able to detect two tumours in Patricia very early on in their development and spare her the rigorous effects of chemotherapy and radiation. This is an incredible outcome,” Dr Padhye said.

“We used to think getting cancer was just bad luck and there was little that could have been done to prevent it so it is really exciting to be able to commence a study where we can use genome sequencing to potentially change treatments and outcomes for some of our families.”

“An early diagnosis means we can give these kids the best chance at a normal childhood. It also fills us with a great deal of hope about what we will be able to achieve in the future,” Dr Padhye said.

The PREDICT Study will be run over the next two - three years and will be offered to all newly diagnosed patients. It is hoped after the completion of the study, genetic sequencing will become part of routine clinical care for all patients.

The PREDICT Study is a collaboration between Sydney Children’s Hospital, Randwick, The Children’s Hospital at Westmead, Luminesce Alliance, Children’s Cancer Institute, Prince of Wales Hospital and Westmead Hospital.