Learning she had advanced bowel cancer at the age of 36 understandably came as a devastating shock to Carla Mitchell – not least because the disease is normally associated with those in their 60s and above.
What the marketing representative from Kent did not know at the time was that she was born with Lynch syndrome – an under-recognised genetic condition that affects up to 200,000 Britons, that significantly raises their risk of numerous cancers early in life.
Those with Lynch syndrome have mutations in one of four genes – MLH1, MSH2, MSH6 and PMS2 – that normally help repair DNA errors in cells. The mutations instead mean cells are more likely to develop into cancer.
As a result, they have a more than a 70 per cent greater risk of cancers affecting the bowel, womb, ovaries, stomach, gallbladder, prostate and urinary tract, according to Cancer Research UK.
Lynch can run in families – so first-degree relatives (parents, siblings, children) of someone with Lynch have a 50 per cent risk of having the genes themselves. Yet if the condition is identified early in life – via genetic screening – carriers can be given advice to help reduce their risk.
For example, taking a daily low-dose aspirin could cut their risk of bowel cancer by 40 per cent, by lowering inflammation that causes healthy bowel cells to turn cancerous.
Yet NHS figures show 95 per cent of Lynch carriers are oblivious to their genetic risk of cancer – and just 5 per cent have been identified.
This is despite the fact that gene-screening tools for Lynch are available in the UK – and that it’s official NHS policy to screen all bowel cancer patients for the condition (yet recent studies show this has been done only patchily).
Now there is more impetus to find people with the syndrome, after the NHS launched a national bowel screening programme earlier this year.
Carla’s crushing diagnosis came out of the blue in 2021.
‘Looking back there were red flags – I was unusually tired but it was at the end of lockdown so I attributed that to being less physically active and my hectic work schedule.
‘But it wasn’t a sort of tiredness I’d experienced before – I felt heavy and my legs would ache. If I tried to run upstairs my heart would race.’
A blood test by her GP revealed her iron levels were low – she was told she was ‘dangerously anaemic and must go to hospital’.
‘It threw me into panic. I’d never been in hospital before’, she said. She was given iron infusions and underwent further tests.
Carla Mitchell was diagnosed with bowel cancer aged 36 in 2021
Days later, on Christmas Eve 2020, her GP called to say they had found blood in her stools and she urgently needed a colonoscopy (an examination of the bowel with a camera).
Within weeks, Carla was diagnosed with stage 3 bowel cancer that had spread to her lymph nodes. She had surgery to remove the tumour, followed by three months of chemotherapy. When her treatment ended in August 2021, a scan found no evidence of cancer.
Only then did anyone mention the possibility of genetic testing for Lynch syndrome.
‘Six months later I had a letter from the genetics team at Guy’s Hospital to say I did have a form of Lynch [a mutation in the PMS2 gene],’ recalls Carla.
‘I did not take the news well – it was tougher than getting my cancer diagnosis. Lynch means that there is always a cloud over my head.’
The National Institute for Health and Care Excellence recommended in 2017 that everyone diagnosed with bowel cancer be tested for the syndrome.
But a report in February by NHS England’s National Disease Registration Service, published in the European Journal of Human Genetics, warned that these guidelines were not being implemented, and as a result doctors were failing to spot up to 700 people a year with Lynch.
Experts believe that women with endometrial (or womb) cancer, another disease linked to the genes, should also be screeened.
‘For many women with Lynch, endometrial cancer is the first cancer they develop,’ Clare Turnbull, a professor of translational cancer genetics at the Institute of Cancer Research in London, told the Mail.
But a study she co-authored, published in October in the BMJ Journal of Medical Genetics, found that only one in eight Lynch syndrome patients was diagnosed through screening of endometrial cancer cases in England in 2019.
Lynch syndrome significantly raises the risk of numerous cancers early in life
Professor Turnbull argues that if Lynch patients are told of their genetic danger, they could benefit from strategies to significantly cut their risk of lethal cancers.
Some experts advise women with Lynch to have their ovaries, fallopian tubes and womb removed once they have finished childbearing – to protect against endometrial cancer, for instance.
Professor Turnbull says greater efforts are also needed to trace the relatives of those affected, as they may well have the condition but be unaware.
Meanwhile, NICE recommends that people with Lynch should also undergo colonoscopy every two years to check for any signs of bowel cancer.
But it’s fraught with difficulty, says Professor Turnbull.
‘Quite a lot of these cancers aren’t easy to spot – they don’t stand out from colon tissue as polyps, for example, as normal bowel cancers do – a lot of them are flat and they hide,’ she says.
But Naser Turabi, director of evidence and implementation at Cancer Research UK, insists screening is ‘extremely effective’ at catching early-stage cancer.
However he concedes that the colonoscopies for those with Lynch need to be more thorough than normal as doctors are ‘looking for something that is often not causing symptoms’.
In February, NHS England announced a world-first: routine bowel cancer screening every two years for those already known to have Lynch syndrome, identified either through families or because they have already had cancer.
The problem is this covers only the 10,000 people in England already on the NHS Lynch syndrome register – not the 190,000 or so as yet undiagnosed.
But NHS England says that this coverage will improve as genetic screening spreads. For example, it says, 94 per cent of people diagnosed with bowel or endometrial cancer in 2021 to last year were tested for Lynch syndrome – up from just 47 per cent in 2019.
But questions remain over how effectively the two-yearly screening is implemented, says Mr Turabi.
‘There is a lot of pressure on genomic services,’ he says. ‘And Lynch tests are not as urgent as, for example, gene testing for lung cancer, where they’d help doctors to determine what specific treatment a patient should get for their particular form of the disease.’
Meanwhile, the need to identify more people with Lynch is becoming increasingly vital as scientists at Oxford University are working on a vaccine that may prevent them getting cancer.
One of the researchers, Dr David Church, a clinical scientist fellow and a medical doctor specialising in oncology, said the vaccine will help patients’ immune systems spot cells that turn cancerous due to Lynch syndrome DNA faults.
‘As the cells proliferate they switch off the protein mechanisms by which the immune system recognises them, effectively cloaking themselves.’
The hope is a jab will ‘turbo-charge’ patients’ immune defences so they can kill rogue cells before they go undercover.
Another line of attack is via the English National Lynch Syndrome Registry, a new database of Lynch patients – it will match the DNA data of patients with their cancer diagnosis, treatment and outcomes, in the hope that this will help clinicians to develop the most effective treatment and prevention strategies.
Meanwhile, Carla’s mother is undergoing the gene-testing process – as Carla, who doesn’t know her father, explains: ‘we don’t know of any cancer in the family, though you can have the mutation and never develop cancer’.
She and her husband Simon would like to have children, and are weighing up their options – especially as she has been advised to undergo a hysterectomy at 45 to prevent endometrial cancer
‘If we do have a child naturally then they have a 50/50 chance of having Lynch,’ she says.
‘With IVF we could have embryos screened to remove any with the Lynch mutation. But IVF can take years.’
But Carla remains resolutely positive.
‘I am confident that there is a future for people with Lynch,’ she says.
‘Even if my child had it, I’m confident that modern medicine will ensure that they have a healthy future.’
