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Gene linked to oestrogen levels and breast cancer risk in younger women




Thursday 5 April 2012


Scientists have found the first direct link between breast cancer risk and genetically-determined levels of the hormone oestrogen in younger women, according to a paper published online this week in the Journal of the National Cancer Institute.



The important study led by scientists at the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research (ICR) and the London School of Hygiene and Tropical Medicine (LSHTM) found an alteration in a gene that is involved in the breakdown of oestrogen and is also associated with a modest reduction in breast cancer risk in pre-menopausal women.



Senior author Dr Olivia Fletcher from the ICR’s Breakthrough Breast Cancer Research Centre said: “This is the first time anyone has found a DNA change that is directly associated both with hormone levels and breast cancer risk in younger women. Scientists have suspected this link exists, but no one has been able to prove it until now. This represents an important step forward in our understanding of the link between hormones and breast cancer. Ultimately, it may have implications for the way we monitor and treat breast cancer.”


Although this DNA change is only one part of a very complex picture of the relationship between hormones and breast cancer, variants such as this could potentially form part of a genetic test that could help predict young women’s risk of breast cancer.


Sex hormones such as oestrogen are known to be important in breast cancer development. Previous studies have found that postmenopausal women with higher levels of particular hormones are at greater risk of breast cancer, however the direct evidence in premenopausal women has so far been inconsistent.



The ICR scientists and colleagues in the UK and Ireland set out to find genetic variants involved in the synthesis or breakdown of sex hormones. They first measured markers of hormone levels in the urine and blood of more than 700 healthy premenopausal women, using a process that was specially designed to account for variation in levels during the menstrual cycle. They then examined the women’s DNA, focusing on 42 genes that are known to be involved in the synthesis or breakdown of sex hormones.

When they compared women’s hormone levels with each of the variants that they tested, they identified one genetic variant that was more common in women who had lower urinary levels of a particular oestrogen breakdown product called oestrone glucuronide. The variant was a single letter change in the DNA at position 7q22.1, not far from the CYP3A gene cluster. It was associated with a 22 per cent reduction in urinary oestrone glucuronide levels.


The team then tested this variant in a further 10,551 breast cancer patients and 17,535 healthy controls, and found the DNA change was more common in healthy women. The variant was associated with a modest – nine per cent – reduction in breast cancer risk in women diagnosed at or before age 50, but not in older women.



One of the family of CYP3A genes, CYP3A4, is responsible for breaking down around half of all clinically used drugs, including some of those used in the treatment of breast cancer, so the team believe their finding may also have wider implications. It is possible that the gene variant may influence the way women respond to drugs.



“As we move towards a future of personalised medicine, we hope to test people’s genes to not only decide which drugs to give them, but also to tailor the most effective doses for the individual. This research has revealed that this set of genes warrants further investigation for the effect they may have on the way the body processes drugs,” Dr Fletcher said.


The study was a collaboration between scientists at the ICR’s Breakthrough Breast Cancer Research Centre and the Division of Genetics and Epidemiology; The Royal Marsden Hospital NHS Foundation Trust; the LSHTM; the Wellcome Trust Centre for Human Genetics; the Biomedical Research Centre at Guy’s & St Thomas’ NHS Foundation Trust and King’s College London; and The University of Edinburgh in the UK along with University Hospital Galway in Ireland.



The study was funded by Breakthrough Breast Cancer, Breast Cancer Campaign, Cancer Research UK and the Department of Health.




Media Contact: ICR Science Communications Manager Jane Bunce on 0207 153 5106 or after hours 077217 47900



Notes to editors


Impact of CYP3A variation on estrone levels and breast cancer risk has published online in Journal of the National Cancer Institute.



Breast Cancer

  • Breast cancer is the most commonly diagnosed cancer in the UK – nearly 48,000 women and around 300 men are diagnosed every year
  • One in eight women in the UK will develop breast cancer at some point in their lifetime
  • More women than ever in the UK are surviving breast cancer thanks to better awareness, better treatments and better screening



Breakthrough Breast Cancer

Breakthrough Breast Cancer funds ground-breaking research, campaigns for better services and treatments and raises awareness of breast cancer.  Through this work the charity believes passionately that breast cancer can be beaten and the fear of the disease removed for good. Find more information at



Cancer Research UK

  • Cancer Research UK is the world’s leading cancer charity dedicated to saving lives through research
  • The charity’s groundbreaking work into the prevention, diagnosis and treatment of cancer has helped save millions of lives.  This work is funded entirely by the public.
  • Cancer Research UK has been at the heart of the progress that has already seen survival rates in the UK double in the last forty years.
  • Cancer Research UK supports research into all aspects of cancer through the work of over 4,000 scientists, doctors and nurses.
  • Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.


For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 3469 6699 or visit


Breast Cancer Campaign


  • Breast Cancer Campaign aims to beat breast cancer by funding innovative world-class research to understand how breast cancer develops, leading to improved diagnosis, treatment, prevention and cure
  • The charity currently funds 86 projects worth over £14.9 million in 37 locations across the UK and Ireland


The Institute of Cancer Research
(ICR) is one of the world’s most influential cancer research institutes.

Scientists and clinicians at the 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



London School of Hygiene & Tropical Medicine

The London School of Hygiene & Tropical Medicine is a world-leading centre for research and postgraduate education in public and global health, with 4000 students and more than 1300 staff working in over 100 countries. The School is one of the highest-rated research institutions in the UK, and was recently cited as one of the world’s top universities for collaborative research.  The School's mission is to improve health and health equity in the UK and worldwide; working in partnership to achieve excellence in public and global health research, education and translation of knowledge into policy and practice.

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