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deCODE Genetics, in Collaboration with Academic Colleagues and Illumina, Discovers Mutations Conferring High Risk of Ovarian Cancer


News provided by

DeCODE Genetics Inc

Oct 02, 2011, 01:05 ET

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REYKJAVIK, Iceland, October 2, 2011 /PRNewswire/ --

Scientists at deCODE Genetics and academic collaborators from Iceland, The Netherlands, Spain and Finland today report the discovery of variants in the human genome that associate with  increased risk of invasive ovarian cancer, one of the deadliest forms of cancer in women.  The study was done in collaboration with Illumina, Inc., and is published today in the online edition of Nature Genetics.

Using Illumina sequencing technology, deCODE scientists determined the sequences of the entire genomes of 457 Icelanders, and identified 16 million single nucleotide polymorphisms (SNPs). Through a combination of SNP genotyping and computational techniques utilizing the extensive Icelandic genealogy, they were able to propagate those 16 million variants into over 40,000 Icelanders, including over 600 patients with ovarian cancer.

The researchers observed a rare sequence variant in a gene named BRIP1 that confers more than eightfold increase in the risk of ovarian cancer in the Icelandic population.  BRIP1 plays an important role in maintaining the stability of the genome and interacting directly with the DNA repair protein encoded by the known breast cancer gene BRCA1.  Interestingly, the mutation also associates with increased risk of being diagnosed with cancer in general, and individuals carrying the variant live 3.6 years fewer on average.

The researchers also searched for mutations in the BRIP1 gene in ovarian cancer patients in other populations.  A rare variant in BRIP1 was found in a Spanish cohort of 144 patients and 896 controls; this mutation confers a significantly increased risk of not only ovarian cancer, but also breast cancer.  Finally, examination of  tumors from ovarian cancer patients that carry the mutation showed a loss of the healthy copy of the gene, further supporting the role of BRIP1 as a classical tumor suppressor.

"This study underscores the important contribution that the Icelandic population can make to the discovery of low frequency sequence variants with large effect.  The potential to do this has been clear since the critical role played by Iceland in the discovery of the BRCA2 gene.  Until now, however, the combination of sequencing technology and analytical techniques were insufficient to unleash the flood of discoveries that we and our collaborators are now making," said Kari Stefansson, deCODE's CEO and senior author of the study.  

"Our objective is to translate our discoveries most rapidly into benefit for patients.  So, we are committed to working with our collaborators, as we did in this case, to identify the spectrum of mutations occuring in other populations.  This allows us to use the Icelandic resource as a unique discovery cohort, and then quickly elucidate the broader utility," Dr. Stefansson added.

Ovarian cancer causes more deaths than any other gynecologic malignancy in developed countries.  Five-year relative survival rate is less than 45%, with the stage at diagnosis being the major prognostic factor.  Importantly, only 19% of ovarian cancer cases are diagnosed while the cancer is still localized and chances of cure are over 90%.  Hence, the discovery of genetic variants that increase the risk of ovarian cancer may enable the development of diagnostic tests to identify women at high risk for the disease.  Women at high risk can then be be offered frequent screening for early detection and treatment or preventive intervention.  

About deCODE

Headquartered in Reykjavik, Iceland, deCODE genetics is a global leader in analyzing and understanding the human genome. Using its unique expertise and population resources, deCODE has discovered genetic risk factors for dozens of common diseases ranging from cardiovascular disease to cancer.

In order to most rapidly realize the value of genetics for human health, deCODE is currently partnering with life sciences companies to accelerate their target discovery, validation, and prioritization efforts, yielding improved patient stratification for clinical trials and essential companion diagnostics. In addition, through its CLIA- and CAP-certified laboratory, deCODE offers DNA-based tests for gauging risk and empowering prevention of common diseases.  deCODE also licenses its tests, intellectual property, and analytical tools to partner organizations.  deCODE's corporate information can be found at http://www.decode.com with information about our genetic testing services at http://www.decodehealth.com and http://www.decodeme.com

Contact:
Gisli Arnason          
+354-570-1825
[email protected]

SOURCE DeCODE Genetics Inc

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