“A new disease”: Young women disproportionately affected by adverse cancer gene mutation

Australia has highest rates of early-onset bowel cancer in the world, and new research confirms an aggressive variant is disproportionately affecting young women.

New Australian findings from the COALA study reveal that a specific genetic mutation, known as BRAFV600E, has a disproportionate prevalence in young female patients with metastatic bowel (colorectal) cancer (mCRC).

Leading medical oncologist and Bowel Cancer Australia spokesperson, Dr Prasad Cooray, says that the findings suggest “this is actually a new type of a disease”.

The COALA study, which examined around 3,000 cases of bowel cancer diagnosed between 2009 and 2025, found one in four mCRC patients under 40 years of age had this BRAF-mutation. Alarmingly, the study showed the mutation is far more common in young women than men – at a ratio of almost two to one.

Dr Cooray explains this mutation makes the cancer “biologically aggressive” as it becomes harder to treat and is often resistant to chemotherapy and other options. It is also complicated by the fact bowel cancer in younger patients is often only diagnosed at Stage 4, so has already spread to multiple organs, leading to significantly shorter overall survival.

“This disease affects far too many young women, and it is especially a problem as women tend to get pregnant between 25 and 40 years of age,” observes Dr Cooray. “So, as a result, we have this large number of women getting bowel cancer during pregnancy or soon after.”

Metastatic bowel cancer, an advanced stage of colon or rectal cancer where the cancer has spread (metastasised) from its original site to other organs (most commonly the liver, lungs or lymph nodes) is now the deadliest cancer among Australians aged 25 to 54.

Led by Dr Nadia Hitchen, Medical Oncology Fellow at Peter MacCallum Cancer Centre, the COALA study authors noted this was the first study to emphasise the disproportionate impact of adverse mutations on very young patients.

Such research “highlights that this early-onset bowel cancer is actually a very different type of a disease to normal bowel cancer,” says Dr Cooray.

“As an oncology community, we are still trying to fit it into the late-onset bowel cancer paradigm, when we need to see this as a new type of disease,” he says. “Patients have a different mutation profile; they have a much higher BRAF prevalence. Females are affected much more than males.

“The traditional risk factors for bowel cancer – being overweight, excessive alcohol use, sedentary lifestyle, lack of exercise, high intake of processed meat – don’t apply to these patients. These are really fit, working people. Some are even athletes, so we need to apply a new framework of looking at it and treating it as a new disease.”

While Stage 4 bowel cancer is typically considered incurable, Dr Cooray’s own team has shown outcomes can be dramatically improved with intensive, multi-disciplinary treatment.

“The standard cure rate for Stage 4 bowel cancer is about 13 per cent,” he explains. “But with young patients, if we optimally use surgery, chemotherapy, radiation – using existing treatments in a smarter, more coordinated way – we can cure up to 60 per cent. That’s an extraordinary difference.”

Despite these breakthroughs, Australia lacks a comprehensive national registry to track early-onset bowel cancer. The current datasets capture only a fraction of the estimated 1,500-1,800 cases diagnosed each year.

Dr Cooray argues that real-time data collection is essential to guide treatment and policy. “It’s like driving with a 10-year-old map,” he says. “We need the updated version now.”

Although the cause of this disease remains unknown, and reform is required, the good news is that lives can be saved today. “But to do so, we must change our mindset, collect better data, and recognise this as the distinct disease that it is,” he says. “A disease that demands a new paradigm.”