A new research programme will lay the foundations for routine testing for inherited cancer genes in patients with the disease.
Changes in certain genes, known as cancer predisposition genes, greatly increase the chances of a person developing cancer. Knowing whether a patient carries such a gene can affect decisions as to how treat them.
There are almost 100 known cancer predisposition genes, but at present testing for them in the UK is done on an ad hoc basis, with patients referred to a genetics service if they are suspected of having an ‘inherited’ cancer.
Under the new Mainstreaming Cancer Genetics programme, initially involving patients with breast or ovarian cancer patients at the Royal Marsden in London, screening for cancer predisposition genes will be done routinely.
The genetic testing will be managed by the patient’s cancer doctor, rather than by referring them to a genetics clinic. It will be rolled out to patients with other cancer types over the next few years.
The ultimate aim is to develop a ‘toolkit’ to share with other parts of the NHS, allowing them to set up similar services for patients.
The programme is being led by a team at The Institute of Cancer Research, in partnership with The Royal Marsden, Illumina Inc, and the Wellcome Trust Centre for Human Genetics, which provided £2.7m of funding.
Professor Nazneen Rahman, head of genetics at the Institute of Cancer Research (ICR), said it was “very important” for doctors to know if a inherited change in a patient’s genetic blueprint had caused their cancer.
Testing allows for more personalised treatment, since a patient with a cancer predisposition gene may face a higher risk of developing a subsequent second cancer.
Knowing they have the gene gives them the option of having more comprehensive surgery, taking different medicines, or receiving extra monitoring.
The screening programme could also provide useful information about the cancer risks of a patient’s relatives.
“Sometimes a relative is found to also have an increased risk of cancer and screening or preventative measures can be employed,” Dr Rahman added.
“Just as frequently, testing provides the reassuring news that a relative is not at increased risk of cancer and does not need interventions.”
The new programme will use a new test, developed in conjunction with Illumina Inc, that takes advantage of new sequencing methods.
The TruSight Cancer panel can analyse 97 cancer predisposition genes within a few weeks for the cost of a few hundred pounds and will be ready for use in the clinic in 2014.
Professor Peter Johnson, Cancer Research UK‘s chief clinician, said researchers now have a wealth of information about the inherited gene faults that increase a person’s cancer risk, and this knowledge can help tailor treatments for patients whose cancers are linked to these mutations.
“This exciting new initiative will help embed genetic testing into routine NHS cancer care, and hopefully allow more cancer patients to benefit from such testing – and more personalised care – in the future,” he added.
Patients will be tested for inherited faults in their body’s DNA that might be linked to their cancer, rather than faults in the tumour itself.
That will complement initiatives such as Cancer Research UK’s own stratified medicine programme, which aims to analyse the faulty genes driving a patient’s tumour, paving the way for doctors to tailor treatments to their type of cancer.
“Together, these programmes will help revolutionise the way cancer is managed in the NHS, and bring forward the day when all cancers are cured,” Professor Johnson added.
A new £100m project will map the DNA of up to 100,000 patients with cancer and other rare diseases.
The genetic data will help researchers to develop new drugs and tests that could help save thousands of lives.
Britain should “push the boundaries” and become the first country to introduce genetic sequencing to its mainstream health service, according to the prime minister David Cameron.
He said: “Britain has often led the world in scientific breakthroughs and medical innovations, from the first CT scan and test-tube baby through to decoding DNA. By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care.We are turning an important scientific breakthrough into a potentially life-saving reality for NHS patients across the country.”
He added: “If we get this right, we could transform how we diagnose and treat our most complex diseases not only here but across the world, while enabling our best scientists to discover the next wonder drug or breakthrough technology.”
Dr Harpal Kumar, Cancer Research UK’s chief executive, welcomed the plans: “This work will uncover a wealth of new information which doctors and scientists will use to learn more about the biology of the disease and to develop new ways to prevent, diagnose and effectively treat cancer.
“We’re very excited about personalised medicine – some targeted treatments, such as imatinib, a drug for chronic myeloid leukaemia are already helping to treat patients more effectively – and we’re working hard, with many others – to develop new treatments, and to ensure the NHS can effectively deliver a more personalised cancer treatment service.”
He added: “We hope that this vital investment, together with other measures, such as continued support to diagnose cancers earlier, when treatment is more likely to be successful, will be an important step towards saving more lives from cancer, sooner.
“But, it will be some time before everyone with the disease will be able to have treatment based on the genetic make-up of their cancer.”
The NHS already analyses single genes in cancer tests to determine the chances of particular patients having side-effects from treatment.
Professor Dame Sally Davies, the government’s chief medical officer, explained: “At the moment, these tests focus on diseases caused by changes in a single gene.
“This funding opens up the possibility of being able to look at the three billion DNA pieces in each of us so we can get a greater understanding of the complex relationship between our genes and lifestyle.”
The £100m earmarked from the project, which stems from existing NHS budgets, will be spent on training genetic scientists, mapping patients’s DNA, and creating systems for handling the information.
The Human Genome Project, which made an initial ‘rough draft’ of the human genetic sequence in 2011, cost approximately £500m.
But technological advances have cut costs dramatically, meaning the procedure can now be performed for under £1,000 per person, and officials believe the new £100m DNA mapping investment could reduce prices further still.
All patients will be asked for permission before their DNA is sequenced, with all subsequent data anonymised before it is stored.
Alongside the DNA mapping announcement, the government also allocated £100m of new science funding in the Autumn Statement to the life sciences sector.
The money will help build research capabilities for synthetic biology, facilities for manufacturing cell and biological medicines such as antibodies and vaccines.
Science minister David Willetts said: “Life sciences is one of the most truly international sectors – so if we are to continue to be a world player and compete in the global race we must do everything we can to support it.
“In the past year, our initiatives have attracted more than £1 billion of private sector investment to the UK. We can see clear evidence the UK is succeeding in creating the right environment to attract global investment to our shores and continue to be world leader in life sciences.”
Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests
Introduction The Bowel Cancer Screening Programme in England began operating in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. The programme aims to reduce mortality from colorectal cancer by 16% in those invited for screening.
Methods All subjects eligible for screening in the National Health Service in England are included on one database, which is populated from National Health Service registration data covering about 98% of the population of England. This analysis is only of subjects invited to participate in the first (prevalent) round of screening.
Results By October 2008 almost 2.1 million had been invited to participate, with tests being returned by 49.6% of men and 54.4% of women invited. Uptake ranged between 55–60% across the four provincial hubs which administer the programme but was lower in the London hub (40%). Of the 1.08 million returning tests 2.5% of men and 1.5% of women had an abnormal test. 17 518 (10 608 M, 6910 F) underwent investigation, with 98% having a colonoscopy as their first investigation. Cancer (n=1772) and higher risk adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of women investigated, respectively. 71% of cancers were ‘early’ (10% polyp cancer, 32% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with only 14% being right-sided compared with expected figures of 67% and 24% for left and right side from UK cancer registration.
Conclusion In this first round of screening in England uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials. Although there was the expected improvement in cancer stage at diagnosis, the proportion with left-sided cancers was higher than expected.
Significance of this study
What is already known about this subject?
Randomised trials of colorectal (bowel) cancer screening have indicated that a biennial guaiac-based faecal occult blood test has the potential to reduce colorectal cancer mortality by about 25% in those accepting screening and by 16% in those offered screening.
In the UK trials and pilot studies uptake was between 50% and 60%.
Factors such as age, ethnic background, deprivation and gender are known to influence uptake.
What are the new findings?
Overall uptake in this first round of screening was 55–60% in the provinces in keeping with previous studies but was much lower in the London area at only 40%.
Uptake of the offer of colonoscopy in those with an abnormal test was high but only 83% of those with abnormal tests underwent colonoscopy.
Early cancer (Dukes A or B) was found in 70% of those with cancer.
The proportion of screen-detected cancers that were found in the right colon was lower than expected.
How might these impact on clinical practice in the foreseeable future?
If these early results are maintained the Bowel Cancer Screening Programme will achieve the intended 16% reduction in overall bowel cancer mortality.
Different screening strategies may be required to effectively screen for right-sided bowel cancer.
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