High risk of ovarian cancer gene found In landmark study

Women with a defective copy of a DNA repair gene called RAD51D have a 1 in 11 risk of developing ovarian cancer compared to 1 in 70 among the general population, according to a landmark Cancer Research UK-funded study led by Professor Nazneen Rahman at the Institute of cancer research (ICR) published in the 7 online August issue of nature genetics. There is hope that personalized treatment will be available earlier than usual, because a class of drugs already developed showed promise in targeting affected cells.

Rahman, who is Professor of human genetics and Chair of Cancer Genetics section on ICR is told the press the study represents an important step forward in our understanding of how faulty genes contribute to the development of some cases of ovarian cancer, and there is "real hope on the horizon that drugs are specifically focused on the gene will be available".

RAD51D repairs damaged DNA. When the gene is defective, an important repair process fails, leaving damaged DNA in cells, they build that increases the risk of cancer will be.

Rahman and colleagues for their study examined DNA, of women in 911 families with ovarian and breast cancer and compared with the DNA from a control group of 1.060 people among the general population (the controls).

They eight RAD51D inactivating mutations in unrelated women with cancer, compared with only one found in the controls.

The Association was primarily with ovarian cancer, with three mutations found in 59 of the families with three or more persons with ovarian cancer.

The researchers found also shortage of RAD51D cells are sensitive to treatment with a relatively new class of cancer drug known as a PARP inhibitor, "suggest a potential therapeutic approach for cancers occur in RAD51D mutation carriers", they write.

PARP inhibitors are a group of drugs that inhibit the action of the enzyme Poly ADP ribose polymerase (PARP), a protein that plays a role in many cell processes relating to DNA repair and programmed cell death.

PARP inhibitors are already promising results will not appear in clinical trials for the treatment of breast cancer and cancer of the ovaries with mutations in the BRCA1 and BRCA2 genes, which are also involved in the repair of damaged DNA.

Ovarian cancer is the fifth most common cancer in women. In the United Kingdom are annually about 6,500 women diagnosed with the disease. However, often develops without any clear symptoms, so unfortunately, that many women find that they only have it once it has spread to other parts of the body, by which time the chances of survival are much worse.

The researchers estimate that the mutations of the RAD51D they discovered in barely 1% of women with ovarian cancer, affect approximately 50 persons in the United Kingdom each year.

Rahman said:

"Women with an error in RAD51D gen have a one in 11 chance of developing ovarian cancer. At this level of risk, women may want to consider their ovaries removed after children, to prevent ovarian cancer. "

Professor Nic Jones, chief scientists at Cancer Research UK, said that it was "incredibly exciting to discover this gen high risk for ovarian cancer".

"It is further evidence that a range of different high risk genes cause the development of breast and ovarian cancer and we hope that there are more waiting to be discovered in various forms of cancer," said Jones, adding that they believe that "the results of this research will help inform personal treatment approaches and give doctors better informed about the risks of cancer patients to tell".

Harpal Kumar, chief executive of Cancer Research UK said:

"All of our research is generously funded by the public. This support has enabled us to invest in the identification of DNA modifications that a picture of which parts of a person's gene sequence are linked to cancer. This life-changing discovery illustrates the importance of this research and the importance of ongoing public support. "

Last year, Cancer Research UK more than 12 million pounds of public funds donated on addressing of ovarian cancer. The charity is the largest single funder of research into the disease in the United Kingdom.

Written by Catharine Paddock, PhD
Copyright: Medical News today
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Article reference:
"Germline mutations in RAD51D grant sensitivity for ovarian cancer."
Chey Loveday, Clare Turnbull, Emma Ramsay, Deborah Hughes, Elise Ruark, Jessica R Frankum, and others.
Nature Genetics, published online August 07 2011; DOI: 10.1038/ng. 893
Link to article.

Additional resources: Cancer Research UK, the Institute of cancer research.