Genetic mutation linked to men’s cancer

VICTORIAN researchers have uncovered a new key reason why men are more likely than women to get — and die from — cancer.

Scientists from the Peter MacCallum Cancer Centre have found a common gene mutation on the X chromosome, involved in more than half of all human cancers, occurs more often and has greater potency in males.

The researchers say their finding paves the way for consideration of a patient’s gender to play a larger role in deciding the best treatment course and assessment of cancer risk, as well as in developing new treatments.

One in two Australian men and one in three women will be diagnosed with cancer, with the death rate up to 60 per cent higher in some cancers for men.

But even when matched for known cancer risk factors, such as weight, smoking status and age, this higher risk for males remains and is largely poorly understood.

Peter Mac’s tumour suppression laboratory used a new data analysis technique to compare the incidence of the 12 most common non-reproductive cancers in the US — including liver, head, lung, melanoma and oesophageal — with the rates of the TP53 gene mutation.

This gene is the body’s major anti-cancer protein, with its main job to trigger the programmed death of damaged cells to save tissues and organs.

“In its normal function, it’s highly protective of cancer,” said co-lead author Dr Sue

Haupt. “If it becomes mutated, it doesn’t just lose its capacity to fight against cancer, it becomes a tumour driver.

“We consider it a Jekyll and Hyde circumstance.”

Their analysis, driven by PhD student Franco Caramia, found that in some cancers men were up to five times more likely to have that gene mutation than women.

They also found a group of genes on the X chromosome that could affect the activity of this anti-cancer protein, even if the cancer didn’t have a genetic mutation.

And while females were less likely to carry a mutated TP53, they were also found to process a “genetic shield” giving them extra protection from having this tumour-driving defect.

“We think this is a fundamental finding that could drive a rethink of personalised medicine,” Dr Haupt said.

“We’ve now linked with clinicians, starting with lung cancer, to find genetic signatures that would help us predict treatment responses — or a sparing of treatment — for different groups.”