'Everyone acknowledges we've shown the proof of concept': The fight for a population-based DNA screening program

Around one in 50 patients might unwittingly have a genetic time bomb — a gene variant that places them at substantially increased risk of early-onset cancer or heart disease.

Most will not know until they are diagnosed with late-stage disease.

The solution? Population-level DNA screening, says Associate Professor Jane Tiller, an associate professor in genomics and policy at Melbourne’s Monash University.

As co-lead of the DNA Screen study, she has helped build a case for preventive genetic screening of Australian adults.

In the pilot study, 10,263 adults aged 18-40 were tested for variants in single genes considered ready for population screening.

They included the BRCA1, BRCA2 and PALB2 genes linked to hereditary breast and ovarian cancer; the MLH1, MSH2 and MSH6 genes linked to Lynch syndrome — which predisposes to bowel, endometrial and other cancers — and familial hypercholesterolaemia-linked genes (LDLR, PCSK9 and APOB).

Some 202 participants were found to be at high risk because of one of these genetic variants.

“That’s 2% of the population for just three conditions,” says Professor Tiller.

“More than half of them have no family history.”

But three-quarters of these high-risk participants were ineligible for government-funded genetic testing under current criteria, which require a diagnosis or a very strong family history.

In the wider community, it is estimated that 90% of individuals at risk for the three conditions remain undetected.

“These conditions are not only high risk; they’re high risk for young people,” says Professor Tiller.

“People in their 30s and 40s are getting cancer before they’re in screening programs for breast or bowel.”

Several participants had previously sought genetic testing based on family history but were refused because their family history failed to reach the threshold.

Among them was a young woman whose mother died of breast cancer, despite being diagnosed at stage 2, when she was 12 years old.

“This young woman spent her 20s trying to get screening, trying to get testing, but was told she wasn’t eligible.

“She came through our study, and when she was 29, we found she had a BRCA2 variant.”

This meant she was eligible for yearly MRIs from 30.

“She turned 30 at the end of last year. She had her first MRI, rang me and said, ‘I’ve got breast cancer.’”

Within a few months, she underwent a double mastectomy.

“We hope she’ll be okay. If she hadn’t come through our program, she wouldn’t have found the cancer at this stage.

“In all likelihood, she might not have found it until it was stage 4.

“It shows the power of our program.”

The Federal Government has not committed the funding needed for DNA Screen to screen a further 100,000 young adults and start the “bridge” between research and rollout of a national DNA screening program, potentially as early as 2030.

With around $50 million, this would identify around 2000 high-risk individuals.

Modelling — detailed in DNA Screen’s pre-budget submission — suggests this testing would be cost-effective at around $300-$400 per test and that population-based DNA screening for the three conditions would result in a $3 billion net productivity gain.

Australia, once a world leader in this area, is now falling behind similar countries — the UK and Canada — that are rolling out larger-scale pilot programs, Professor Tiller warns.

“When we did this pilot study, we were the first in the world.

“But we are quickly falling behind.

“We have this problem in Australia, which is that the research funding to translation pipeline doesn’t exist.

“Everyone acknowledges that the study’s been highly successful, and that we’ve shown proof of concept and that it’s ready to move into the next phase — and there is no pathway to implementation.”

Professor Tiller continues: “These are genes we’ve known about for decades.

“The question isn’t ‘Does population screening work?’ The question is how we implement this into the healthcare system and what are the downstream needs.

“Those include genetic services and interventions.

“If you have Lynch syndrome and you’ve got a high risk of bowel cancer, you’ll need a yearly colonoscopy because you are more likely to develop cancerous polyps at an earlier age.”

Professor Tiller says the public wants DNA screening.

In 2022, when the pilot was flagged in a media story, 10,000 people signed up overnight.

In total, more than 30,000 people wanted to join the study.

But funding to expand the program is just one part of the puzzle.

Cascade testing — ensuring family members of a known case are made aware of their potential genetic risk — also needs to be bolstered, according to Professor Tiller.

“We estimate about three high-risk relatives per proband. So, if we find 6000 more people, it ends up being 8000 high-risk people.

“That’s a huge number.

“Cascade testing is the lowest hanging fruit of preventive genomics.

“Once we find the first person, the proband, all these high-risk people are easy to find.”

During the DNA Screen pilot, it fell to genetic services to provide high-risk participants with a letter outlining the findings that they could provide to relatives, or to encourage them to share the information with family.

But it is a drain on genetic services, which are already struggling with long waiting lists.

“In the next iteration, we would really like to have a cascade testing arm where we contact relatives to let them know about the opportunity to have a test,” Professor Tiller says.

The importance of efficient cascade testing was highlighted in the UK when Adam Ankers, the teenage son of anaesthetist Dr Alastair Ankers, collapsed on a football pitch in January 2024.

Bystanders did not recognise the significance of agonal breathing and failed to deploy the automated external defibrillator, despite it being brought onto the field.

He died four days later with hypoxic brain injury.

An autopsy revealed arrhythmogenic right ventricular cardiomyopathy. It subsequently emerged that it came from his paternal side.

The case was doubly tragic because cascade testing failures meant his family were unaware that a familial genetic risk had been identified.

Adam’s paternal grandmother’s cousin had been diagnosed with arrhythmogenic right ventricular cardiomyopathy in 2018.

This cousin told Adam’s grandmother, but not until four years later.

His grandmother duly alerted Royal Papworth Hospital in England when she was admitted for an ablation. She was referred back to the hospital for screening.

However, an undisclosed error meant an appointment was never made.

Understandably, Dr Ankers is lobbying for an overhaul of the cascade testing system.

Dr Ankers, who has since been found to carry the same gene variant as his son, told The BMJ that the current system relied too heavily on the ability and willingness of someone who has been diagnosed with an inherited condition to contact relatives.

“It is just insane. We are relying on people who may not have had contact with relatives to hand over letters [from clinics],” he said in May.

The subsequent inquest report highlighted that cascade communication reached only about half the families who needed to be made aware.

While Adam’s condition is not linked to the genes tested for in Professor Tiller’s study, she hopes the report has a ripple effect here in Australia.

“The recommendations that have been made around cascade testing haven’t been made anywhere else. Certainly, in Australia, it hasn’t had that kind of attention or been a priority.

“I think it would be beneficial to have that kind of public health mandate that tells genetic, clinical and primary care services this isn’t just something you do if people feel like it.

“I think what’s come out of the UK is great — it will be interesting to see how it changes practice.

“I often hear from genetic counsellors that people say they are not ready to tell their family because they think Mum might worry or Uncle Bertie won’t want to know.”

Another issue is that doctors feel they are powerless to alert relatives of a patient who has been diagnosed with a high-risk genetic variant.

For example, a patient with a BRCA1 or BRCA2 variant could ask a GP to write to her sister on her behalf because they are estranged, or say she does not want her family to know out of fear they will not cope, or even out of spite.

Professor Tiller says this reluctance to intervene often stems from the misconception that privacy laws require doctors to have the permission of both the patient and recipient to share genetic results.

“We end up with these situations where someone who doesn’t know this information dies whose life could have been saved.

“That’s not how the Privacy Act is supposed to work.

“Clinicians aren’t lawyers. They go off what they think they know or what they’ve heard from someone else. They are very cautious about ever doing anything that could look like a breach of privacy.

“What we’ve found is that, of course, people would want to know. They’d be angry if they weren’t told they were at high risk because doctors were worried about privacy.

“A small number say they wouldn’t want to be contacted, but of course, they are always free not to have testing.”

Professor Tiller, a lawyer, successfully sought clarification from the Office of the Australian Information Commissioner to confirm her understanding that federal privacy laws allow clinicians to contact family members to prevent a serious threat to their life or health — even without the patient’s permission.

The commissioner agreed with her interpretation.

“They updated their online guide to privacy to confirm that the intention of the act is to facilitate this.”

Professor Tiller is now seeking clarification around state and territory privacy laws.

“We have a health system that’s very focused on individual rights. We don’t always focus on what’s best for the population.

“Genetic information is not just personal for the individual. It is highly relevant to their relatives and we should be thinking more broadly about the benefit of genetic information, rather than saying, ‘It’s up to you, the patients, to decide if your family can know.’”

In the future, Professor Tiller would like to see GPs take a greater role in adult genetic screening.

“We need to move this kind of screening into preventive care. We need to start bringing primary care into this.

“At the moment, if you have genetic testing for familial hypercholesterolaemia, that is meant to be done through a GP.

“But GPs aren’t doing it because they’re not well educated on those risks, what to look for and why people should be tested for this kind of thing.

“With things like BRCA1/BRCA2, there is still a need for specialists, but we need to educate GPs and also start involving them in the care.”

What do patients want?

Most people would welcome a letter from a GP or other clinician alerting them that they are at risk of a health condition that could be prevented or detected and treated early, according to a study co-authored by Associate Professor Jane Tiller.

In a survey of 1030 people, published in the European Journal of Human Genetics, 85% said they would want to be contacted.

As for how they wanted the information presented, the majority preferred a letter with more specific information about the variant and the associated health conditions.

Only about 20% preferred a letter with less specific information and the option to find out more.

As for how they wanted to be contacted, 45% would prefer a letter direct from a clinician, with 23% wanting both a letter from a clinician and contact from their affected relative.

A letter by post was the most preferred form of contact (40%) followed by email (23%) and a phone call (21%).

As for privacy, nearly all (95%) said they would have no or little concerns if they were sent a letter by a health professional outlining their possible genetic risk.

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