Gene may worsen cancer outcome by speeding metabolism of drugs
Some patients with breast cancer, lung cancer and leukaemia seem to fare poorly after treatment because of the effects of a particular gene, a new study finds.
The gene, called CYP3A7, is normally only active in infancy, but in some people it continues to be switched on into adulthood, and over-activates their metabolism.
Adults with active copies of the gene produce enzymes that break down hormones and about half of all clinically used drugs – potentially reducing the effectiveness of some cancer treatments.
Scientists at The Institute of Cancer Research, London, found that 7-8 per cent of around 2,500 cancer patients analysed had a cluster of single-letter variations in their DNA code causing CYP3A7 to be active in adults.
If the results are confirmed in other studies, they could help to suggest ways of better optimising cancer treatments for patients with this version of the CYP3A7 gene.
The study, published today (Thursday) in the journal Cancer Research, was funded by organisations including Breast Cancer Now, Bloodwise and Cancer Research UK.
The researchers set out to determine whether the cluster of genetic variants – which had previously been associated both with levels of the female sex hormone oestrogen and with risk of developing breast cancer – was also associated with an increased risk of poor cancer outcomes.
They carried out a series of analyses on samples from 1,008 women with breast cancer treated at The Royal Marsden NHS Foundation Trust, 347 patients with lung cancer and 1,128 with chronic lymphoid leukaemia.
The scientists found that 7-8 per cent of patients in each group – breast cancer, lung cancer and leukaemia – carried a specific single-letter genetic 'tag' in their cells which suggested they had the version of the CYP3A7 gene that was still active in adulthood.
They found that in all three groups of cancer patients, the tag was associated with a poor prognosis, possibly because of an effect on the way these patients break down therapeutic cancer drugs.
Among the breast cancer patients, the tag was associated with a 74 per cent increased risk of dying from breast cancer. Among the lung cancer patients, it was associated with a 43 per cent increased risk of death from any cause, and among the patients with leukaemia, it was associated with a 62 per cent increased risk of disease progression.
The study suggests that in the future, modifying standard types or doses of chemotherapy might improve outcomes in carriers of the activating genetic variant for CYP3A7, which is called CYP3A7*1C¬.
Study co-leader Dr Olivia Fletcher, Group Leader in the Breast Cancer Now Research Centre at The Institute of Cancer Research, London, said:
"Our study shows that some patients with breast cancer, lung cancer and leukaemia carry a genetic variant which increases their capacity for breaking down hormones – and potentially drugs. We showed that patients with the variant tend to have worse outcomes than those without, and one possibility is that they are eliminating chemotherapy drugs from the body too efficiently.
"We will need further studies to determine whether the genetic variant is exercising its effect by interfering with treatment, and if so, exactly how it is affecting treatment. Our research won't have an immediate impact on clinical practice, but in the longer term, doctors might be able to take into account the presence of this – and other – genetic variants in planning treatment, in order to make sure that all patients have the treatment that is best for them."
Professor Paul Workman, Chief Executive of The Institute of Cancer Research, London, said:
"Initially, research into cancer genetics was largely concerned with establishing the effects on the risk of developing cancer, but there is now increasingly also a focus on finding out how a patient's genetic background can affect response to treatment.
"This intriguing study suggests that genetic effects on a person's metabolism, and how they process drugs, could have an impact on their outcome after being diagnosed with cancer. In the future, it is likely that genetic testing will form a much more fundamental part of treatment planning for cancer, so that genetic variants like this can be taken into account in choosing the most effective therapy."
Dr Richard Berks, Senior Research Communications Officer at Breast Cancer Now, said:
"It's crucial that people with breast and other cancers receive the most appropriate treatment, tailored to their specific needs.
"This work could help identify cases where certain drugs will not be effective for individual patients, saving that person needless treatment with one drug and opening the door for an alternative that may be more beneficial to them.
"Research into how to use existing drugs more wisely will be critical as we move towards a world of truly personalised medicine, and one in which people no longer lose their lives to breast cancer."
For more information please contact the ICR press office on 020 7153 5380 / [email protected] For enquiries out of office hours, please call 07595 963613.
Notes to editors
Breast Cancer Now thanks Marks & Spencer for their generous contribution towards the work of Dr Olivia Fletcher through their support of the Generations Study.
The Institute of Cancer Research, London, is one of the world's most influential cancer research institutes.
Scientists and clinicians at The Institute of Cancer Research (ICR) are working every day to make a real impact on cancer patients' lives. Through its unique partnership with The Royal Marsden Hospital and 'bench-to-bedside' approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalised cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR's mission is to make the discoveries that defeat cancer. For more information visit http://www.icr.ac.uk
About Breast Cancer Now:
- Breast Cancer Now is the UK's largest breast cancer charity.
- Breast Cancer Now's ambition is that by 2050 everyone who develops breast cancer will live. The charity is determined to stop women dying from the disease, working in a new, collaborative way and bringing together all those affected by the disease to fund research, share knowledge and find answers.
- Breast Cancer Now's world-class research is focused entirely on breast cancer. The charity supports nearly 450 of the world's brightest researchers at more than 20 locations across the UK and Ireland. Together, they're working to discover how to prevent breast cancer, how to detect it earlier and how to treat it effectively at every stage so we can stop the disease taking lives.
- Breast cancer is still the most common cancer in the UK. Nearly 700,000 people living in the UK have experienced a diagnosis and one in eight women will face it in their lifetime. This year alone, more than 50,000 women will be told they have the disease.
- The UK still has one of the lowest breast cancer survival rates in Western Europe and this year alone nearly 12,000 women will lose their lives. It's time to act.
- Breast Cancer Now launched in June 2015, created by the merger of leading research charities Breast Cancer Campaign and Breakthrough Breast Cancer.
- The research centre known previously as the Breakthrough Toby Robins Breast Cancer Research Centre is now known as the Breast Cancer Now Toby Robins Research Centre. The Breast Cancer Now Toby Robins Research Centre, housed in the Mary-Jean Mitchell Green Building, is based at the Institute of Cancer Research in London.
- For more information on Breast Cancer Now's work, visit breastcancernow.org or follow us on Twitter or on Facebook.