A large genetic study has identified 12 new variants commonly associated with the risk of epithelial ovarian cancer.
Early detection of ovarian cancer is crucial in improving the patients' survival rate. If the cancer is diagnosed in the early stages - that is, before it has spread beyond the ovaries - the survival rate is estimated at 92 percent. However, according to the American Cancer Society, only 15 percent of ovarian cancers are diagnosed this early.
New research by an international team of scientists from the United Kingdom, the U.S., and Australia identifies 12 genetic variations that raise the likelihood of epithelial ovarian cancer.
Epithelial ovarian cancer (EOC) is the most common type of ovarian cancer. It forms in the epithelium (the tissue) that covers the ovaries.
The results of the new genomic study were published in the journal Nature Genetics.
Genes account for a third of EOC risk
The new study was conducted as part of the OncoArray Consortium - a large genomic study looking at almost 450,000 samples in an attempt to identify the genetic background for most common cancers.
The OncoArray Consortium used a novel genotyping technique that allowed the researchers to identify nearly 500,000 single nucleotide polymorphisms (SNPs), which are the most common type of variation found in the human genome.
The inherited genetic architecture accounts for a significant portion of a woman's risk of developing EOC, the authors explain.
"We know that a woman's genetic makeup accounts for about one third of her risk of developing ovarian cancer. This is the inherited component of disease risk. We are less certain of environmental factors that increase our risk, but we do know that several factors reduce the risk of ovarian cancer, including taking the oral contraceptive pill, having your tubes tied, and having children."
Prof. Paul Pharoah, co-lead author
Mutations in the BRCA1 and BRCA2 genes make up 40 percent of this risk.
These faulty genes are quite rare - occurring in approximately 1 in 300 people - and correlate with a high incidence of ovarian and breast cancer.
Study finds 12 new variants and confirms another 18
Using data from the OncoArray Consortium, the new study examined the DNA of more than 25,000 people diagnosed with EOC, as well as genetic data from a control group of nearly 41,000 healthy individuals.
Additionally, the researchers investigated more than 31,000 people who had the BRCA1 and BRCA2 genetic mutations, almost 4,000 of whom had EOC.
The researchers located 12 new genetic variants associated with EOC risk. Additionally, the new study confirmed 18 previously identified variants that had been linked to the risk of developing EOC.
Overall, 6.5 percent of the inherited genetic risk of developing EOC is now known.
The first author of the study, Dr. Catherine Phelan from the Moffitt Cancer Center in Tampa, FL, explains what this percentage means:
"Ovarian cancer is clearly a very complex disease - even the 30 risk variants that we now know increase risk of developing the disease account for just a small fraction of the inherited component. We believe that there will likely be many more genetic variants involved, each with extremely small effects. Most of these are likely to be common, but some will be rare."
The authors also note that some women will have multiple risk-associated gene variants, but even combined, these still do not account for more than a 2.8 percent chance of developing ovarian cancer in their lifetimes.
To put this number into perspective, patients who are offered the option to have their ovaries surgically removed as a preventive measure most often have a lifetime risk of at least 10 percent.
However, the researchers also note that a combination of these genetic variants and being a carrier of the faulty BRCA1 and BRCA2 genes might sometimes be enough to call for preventive surgery.
"In some ways, the hard work starts now. We really have little idea of the functional effect these variants have at the molecular or cellular level and so there are few clues as to how they might affect risk. If we can understand how they work, we will be in a better position to treat - and possibly prevent - ovarian cancer."
Dr. Simon Gayther, study co-author