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First step to kidney cancer may occur in childhood, study finds

Scientists unravel the evolutionary roots of one of the UK’s fastest growing cancers.

Seeds of kidney cancer may be planted in childhood or adolescence, decades before the disease is diagnosed, scientists have learned.

The common fault, caused by the botched repair of broken chromosomes, remains hidden and harmless in the majority of the population.

But in an “unlucky” few – a mere 1% or 2% – it combines with other genetic errors to set the cancer time bomb ticking.

A single damaged cell may be all it takes to trigger aggressive and terminal kidney cancer almost a lifetime after the first step towards the disease is taken.

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Dr Peter Campbell, from the Wellcome Sanger Institute in Hinxton, Cambridgeshire, said: “We can now say what the initiating genetic changes are in kidney cancer, and when they happen. What is remarkable is that the hallmark genomic event that characterises kidney cancer takes place on average 40 – 50 years before the cancer is diagnosed.

“These first seeds are sown in childhood or adolescence. Knowing the sequence of events and their timings opens opportunities for intervention.”

Each year around 12,600 people in the UK are diagnosed with kidney cancer and 4,400 die from the disease.

It is one of the fastest growing cancers in terms of incidence, with rates increasing by 50% in the past decade.

Risk factors for kidney cancer include obesity, smoking, high blood pressure and a family history of the disease.

The TRACERx Renal study conducted by scientists from the Francis Crick Institute, University College London, the Royal Marsden NHS Foundation Trust, and Guy’s and St Thomas’ NHS Foundation Trust, looked at the fundamental pathways taken by kidney cancer.

Analysis of 1,000 tumour samples from 100 patients revealed three distinct cancer types that follow different evolutionary routes.

One is slow growing and relatively harmless, another highly aggressive involving rapid explosions of genetic damage, while the third falls between the two extremes.

Ultimately it is hoped the research will lead to a blood test that can flag up an individual’s cancer type and likely fate, opening the door to personalised treatments.

Those patients with the least aggressive cancers could be spared surgery, while those with “born to be bad” tumours would need much more radical therapy.

The work, funded by Cancer Research UK, is reported in three papers in the journal Cell.

Speaking at the Francis Crick Institute in London, Dr Campbell explained the first event that, for some, leads to kidney cancer.

He said: “A couple of chromosomes will shatter and get stitched back together in a different order from when they started.

“What we find is that the chromosomes of these cells when the event happened were pretty virginal. They were pristine untouched chromosomes.

“Through various mathematical approaches we can estimate what the age of the person was when that event  happened. We find that that first event in kidney cancer happens typically in childhood or adolescence, many decades before the cancer is diagnosed.”

He added: “Probably there are a few hundred cells that have that first genetic change; probably all of us are carrying round those few hundred cells in our kidneys once we leave school. And for most of us nothing further will happen to those cells.

“For an unlucky 1 or 2% among us there will be further genetic damage in one of those cells. That next step probably also takes 10 or 20 years to occur on average, and at that stage then the cell has the machinery to expand.

“As it begins to expand it has all the different options it can take to become a fully invasive and terminal cancer.”

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