The research, led by scientists at the University of Cambridge and The Institute of Cancer Research, London, funded by Cancer Research UK and the Wellcome Trust, could lead to new treatments, targeted screening and a greater understanding of how these diseases develop.
The scientists were looking for genetic variations – called single nucleotide polymorphisms (SNPs) – linked to an increased risk of developing cancer.
By studying the DNA make-up of over 100,000 people with cancer and 100,000 people from the general population, they found alterations that were more common in people with prostate, breast or ovarian cancers.
Each alteration raises the risk of cancer by a small amount, but the one per cent of people who have lots of these alterations could see their risk of developing prostate cancer increase to nearly 50 per cent and breast cancer to around 30 per cent.
Study author Professor Doug Easton, from the Centre for Cancer Genetic Epidemiology at the Department of Public Health and Primary Care and the Department of Oncology at the University of Cambridge, said: “We’re on the verge of being able to use our knowledge of these genetic variations to develop tests that could complement breast cancer screening and take us a step closer to having an effective prostate cancer screening programme.
“By looking for people who carry most of these variations we will be able to identify those who are at the greatest risk of getting these cancers and then targeting screening tests to these individuals.”
Many of the SNPs found in the studies were near to areas of the genome that control how certain genes behave. Alterations to these control areas can lead to the ‘brakes’ that stop cells growing out of control being lifted; help cancers spread throughout the body; or help cells grow rapidly out of control. Understanding how these genes are involved in cancer could provide new understanding of how cancers develop and how to treat them.
Professor Paul Pharoah from the Centre for Cancer Genetic Epidemiology at the Department of Public Health and Primary Care, the Cambridge Institute of Public Health (CIPH) and the Department of Oncology at the University of Cambridge, said: "The identification of genetic variants that are associated with cancer risks will give us important insights into the basic biology of cancer that may lead to the development of new therapies or better ways to target existing therapies."
In prostate cancer, 23 of these genetic variations were found, taking the total to 78. Importantly 16 are associated with the more aggressive and life-threatening forms of the disease.
For breast cancer the researchers found 49 SNPs, more than doubling the number previously identified. Some of these were found in regions that have been linked to other cancers, suggesting they are disrupting the same underlying mechanisms that can cause the disease.
And, in ovarian cancer, 11 new regions were found.
As well as looking for the variations that raise the risk of these cancers, the researchers also looked for the SNPs that may influence how different breast cancers behave and regions that influence the cancer risk of people with faults in the BRCA genes.
Carriers of BRCA gene faults are known to be at a greater risk of developing breast and ovarian cancers, but it’s not clear which women will go onto develop cancer. The researchers found that the five per cent of women who have a BRCA1 fault and carry most of the genetic variants linked to BRCA1 have over an 80 per cent chance of developing breast cancer by the age of 80. Women with few of these variants and a BRCA1 fault have a 50 per cent risk of developing the disease.
For women with faults in their BRCA genes this research will mean that soon genetic counsellors may be able to more accurately predict how likely it is that they will develop breast or ovarian cancer.
Dr Kerstin Meyer, Senior Research Associate at the Cancer Research UK Cambridge Institute and affiliated with the Department of Oncology at the University of Cambridge, said: "Current research is identifying many variants in the genome that are associated with breast cancer. My work at the CRUK Cambridge Institute studies the mechanisms underlying these associations. We examine how variants function to regulate specific target genes and what these target genes are. Although some well-known cancer genes have been identified as targets, for example the cell cycle regulator CCND1, we have found that its dysregulation leading to breast cancer risk confounds expectations. Through a better understanding of the biology of cancer risk we hope to find interventions and therapies."
Antonis Antoniou, Cancer Research UK Senior Cancer Research Fellow from the Department of Public Health and Primary Care at the University of Cambridge, said: “Women with BRCA 1 or 2 faults are more likely to get breast or ovarian cancer but have to live with the uncertainty of whether they will actually develop the disease.
“Our research puts us on the verge of being able to give women a much more accurate picture of how likely they are to develop breast or ovarian cancer and would help to guide them about the most appropriate type and timing of prevention or monitoring options for them. We need to now see how it could work in the clinic.”
In a series of accompanying papers the researchers looked for the changes that affect how different types of breast cancer behave. They found a series of SNPs that are only associated with a more aggressive form of breast cancer – called oestrogen receptor negative – suggesting it develops in a unique way, which could open the door to new treatments.
Dr Alison Dunning from the Department of Oncology at the University of Cambridge said: “Once the SNPs were discovered, we next needed to begin working out their mode of action, how some of these genetic changes cause cancer.
“When we examined the numerous genetic changes in the TERT gene, for example, we discovered very little evidence that they cause cancer by altering the length of chromosome end-caps, telomeres – countering previously held beliefs about using telomere length to predict cancer risk.
“These type of genetic discoveries that we made during this study gives us a new, exciting understandings of cancer biology and will hopefully lead to new drug targets.”
Over 80 regions of the genome that can increase an individual’s risk of breast, prostate and ovarian cancers have been found in the largest ever study of its kind.
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