Gene Variant That Increases Ovarian Cancer Risk Discovered

By searching millions of DNA variations in the genomes of thousands of women with and without ovarian cancer, scientists have discovered a previously undetected region of DNA which when altered, can increase a woman's risk of developing ovarian cancer by 40 per cent. The hope is that this will one day lead to a reliable screening test for a disease that currently has a high mortality rate because it is difficult to detect early.

The study was conducted by an international research team that included UK scientists from University College London (UCL), the Cancer Research UK Genetic Epidemiology Unit, and the University of Cambridge, and is published in the 2 August online issue of Nature Genetics.

Ovarian cancer is the fifth most common cancer in women in the UK, where around 6,800 new cases are diagnosed every year, which is a rate of about 130 women a week finding out they have the disease.

However, ovarian cancer is the most common cause of cancer death in women in the UK, where it kills around 4,300 women every year.

The human genome, the DNA-coded blueprint of how to make a human being, has more than 10 million genetic variants, of which just a small number will increase a woman's chance of getting ovarian cancer.

Scientists already know that variants in the BRCA1 and BRCA2 breast cancer genes significantly increase a woman's chances of getting ovarian cancer, but these are rare and account for less than 5 per cent of ovarian cancers.

Senior author Dr Simon Gayther of UCL said this study identified a significant new variant and there is real hope that as more are found:

"We can start to identify the women at greatest risk and this could help doctors to diagnose the disease earlier when treatment has a better chance of being successful."

Gayther and his gynaecological cancer research team's work is supported by funds from Cancer Research UK and The Eve Appeal charity.

For the study the scientists analysed 2.5 million variations in DNA base pairs from the genomes of 1,810 women with, and 2,535 women without ovarian cancer in the UK.

DNA base pairs are like letters of the words that spell out the genetic code. Strips of DNA base pairs (the "words" if you like) are called single nucleotide polymorphisms (SNPs). Small alterations in the coding of particular SNPs, akin to "spelling errors" in words, link to ovarian cancer risk.

After eight years of searching, Gayther and colleagues found an SNP on chromosome 9 that was uniquely linked to ovarian cancer. Each of us has 23 pairs of chromosomes, each "copy" in the pair comes from one biological parent.

In collaboration with the international Ovarian Cancer Association Consortium (OCAC) they confirmed the finding in another group of 7,000 women with ovarian cancer and 10,000 women without the disease. The samples came from women all over the world.

The scientists estimated that:
Women carrying that particular version of the SNP on both copies of chromosome 9 have a 40 per cent higher lifetime risk of developing ovarian cancer than women who do not carry it on either copy of chromosome 9.

The risk for women carrying both copies is 14 in 1,000 compared to 10 in 1,000.

About 15 per cent of women in the UK have both copies of the variant.

Women with only one copy of the variant have a 20 per cent higher lifetime risk of developing ovarian cancer than women who have none.

The risk for women carrying only one copy is 12 in 1,000 compared to 10 in 1,000.

About 40 per cent of women in the UK have one copy.
David Lammy, the Member of Parliament for Tottenham and Minister for Higher Education and Intellectual Property, had particular reason to be interested in this research because it included a DNA sample from his mother, Rose Lammy, who died of ovarian cancer last year. She carried both copies of the DNA variant that Gayther and colleagues identified.

Lammy said the study brings us a step closer toward earlier diagnosis of ovarian cancer, when treatment is more likely to succeed. He told the media:

"I am pleased that Mum's sample was included in this study."

"We now know the fact that she had this altered DNA meant that her lifetime risk had risen from 10 in 1,000 to 14 in 1,000, an increase of 40 per cent compared to those women who don't carry this DNA variation," he added.

"A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2."
Honglin Song, Susan J Ramus, Jonathan Tyrer, Kelly L Bolton, Aleksandra Gentry-Maharaj et al.
Nature Genetics, Published online: 2 August 2009.
DOI:10.1038/ng.424

Source: UCL News.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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