Major screening programs for prostate cancer could be introduced in the wake of a huge international effort by more than 1,000 scientists to unravel the genetic causes of prostate, breast and ovarian cancer.
The study, the largest ever to look for faulty DNA that drives the cancers, revealed scores of genetic markers that can identify people most likely to develop the diseases at some point in their lives.
Doctors said a simple GBP5 spit-test based on the markers could provide patients with a personalized “risk profile” for the diseases and pave the way for individually tailored screening, with those most at risk having more regular health checks.
The findings have major implications for the treatment of prostate cancer: A test based on genetic markers for the disease could identify men whose lifetime risk was a staggering 50 percent, nearly five times the average.
Ros Eeles, professor of cancer genetics at the Institute of Cancer Research in London, described the results as “the single biggest leap forward” in understanding the genetics of the disease.
A screening service could be offered in the UK within five years and would transform medical treatment for the most common cancer among British men. More than 40,000 men a year are diagnosed with prostate cancer in Britain, and nearly 11,000 die from the disease.
Men who are diagnosed with prostate cancer have far greater survival rates when the disease is picked up early. A man diagnosed with early stage prostate cancer has a 95 percent chance of surviving for five years, but the figure falls to 60 percent when the disease is spotted later.
Britain has never introduced a national screening program for prostate cancer because existing tests are not precise enough.
For every life saved by a screening program based on the common PSA blood test, 12 to 48 men would be treated unnecessarily for disease that would never cause problems in their lifetime.
“Genetic profiling will be able to refine the risks in the population so that we can target screening to those at higher risk,” Eeles said.
“We hope that within five years we will be able to use this type of technology in the NHS [National Health Service] to target screening to those who are most likely to benefit,” he said.
Genetic markers are like spelling mistakes in a person’s DNA that raise the risk of disease. To find markers for prostate cancer, scientists compared the genetic make-up of 25,000 prostate cancer patients with a similar number of healthy men. They found 23 new faults in DNA that increase the risk of developing prostate cancer. Importantly, 16 of these drive the most aggressive and life-threatening forms of the disease.
GENETIC FAULTS
While most men carry a small number of the genetic markers for prostate cancer, the 1 percent with the most genetic faults face nearly a five-fold increased risk of the disease. These men have a one in two chance of developing the disease.
Alan Ashworth, the chief executive of the Institute of Cancer Research, said the research “changes the game” for applying genetics to the management of prostate cancer.
“Screening for different levels of risk now becomes a real possibility,” he said.
A similar investigation into breast cancer found 49 new genetic faults that appear to drive the disease. Women who inherit most of these have a 30 percent chance of developing the disease, more than three times the national average. Several of the faults were only predictive of the most aggressive, and dangerous, form of the cancer, called estrogen receptor negative breast cancer.
Women who carry mutations in genes called BRCA are already known to have a substantially higher risk of breast cancer, at around 65 percent. However, the latest study shows that women who have a BRCA mutation and carry many of the newly discovered gene defects are 80 percent more likely to develop the disease.
In the third part of the project, which involved 130 institutions from around the world, scientists compared the genetic makeup of ovarian cancer patients with healthy women. The study found eight new gene regions that raise the risk of the disease, bringing the known total to 12. Together, these had a marginal effect on cancer risk, raising the lifetime chance of disease from 1.8 percent to about 4 percent.
RISK PROFILES
Eeles said a simple test at a GP surgery could be read by a computer to give each patient a personalized risk profile for the disease. Once the tests are available, doctors could improve their accuracy by adding lifestyle factors into the risk assessment.
For example, the risk of breast cancer is raised by alcohol and a high fat diet, but lowered by childbearing and breastfeeding.
Trials are now under way to work out the best way to use the tests, and how any screening programs might work, or be modified where screening already exists.
In the case of prostate cancer, it is not clear at what age men should be tested to determine their risk of the disease. Since prostate cancer usually only develops after the age of 40, a test much earlier might cause unnecessary and prolonged anxiety. It is not clear either whether men who are found to be at high risk should have blood tests or MRI scans, and when doctors should take biopsies.
Tests for breast cancer risk pose similar problems, though screening procedures, such as mammograms, and interventions, from early use of preventative drugs, to a precautionary operation to remove the breasts, are more established.
The work, led by the Institute of Cancer Research and Cambridge University, was funded by Cancer Research UK and the Wellcome Trust charity, and published as a series of papers in Nature Genetics and several other science journals.
While the studies transform what is known about the genetics underpinning the three cancers, in each case, they account for only 40 percent of the gene faults that must be involved. To discover the rest, which could be many thousands, scientists will need even larger studies, and would involve sequencing a person’s entire genetic makeup.
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