Medically reviewed by Alexander Gusev, PhD
A team of Dana-Farber scientists and their associates has identified 34 genes associated with an increased risk of developing earliest-stage ovarian cancer. The findings, published in the journal Nature Genetics, will both help identify women who have the highest risk of developing ovarian cancer and pave the way for identifying new therapies that can target these genes.
Currently, there is no effective screening test for ovarian cancer and the disease is notorious for being detected in later stages when survival rates are poor. However, if ovarian cancer is caught early, survival rates increase dramatically, underscoring the need to identify those who may be at risk for developing the disease.
The study, led by Dana-Farber’s Alexander Gusev, PhD, Simon Gayther, PhD, of Cedars-Sinai Medical Center in Los Angeles, and Bogdan Pasaniuc, PhD, of the University of California at Los Angeles, drew on genetic data gathered over more than a decade by the Ovarian Cancer Association Consortium. The researchers compared the genetic profiles of about 25,000 women with ovarian cancer and 45,000 women without the disease and found more than 30 regions of the genome associated with ovarian cancer.
The next task was to pick out the specific genes within those regions that are responsible for the increase in ovarian cancer risk.
“The main challenge has to do with the number of genes that are in one region of the genome,” explains Pasaniuc. “Whenever you inherit a piece of DNA from your parents, you don’t inherit just every base pair of the genome, you inherit big chunks. That means that if you inherit a gene mutation in a given region, you inherit the entire region, which can carry 10 to 20 genes at a time. This makes it very hard to pinpoint specific genes from specific regions.”
Detective work
The team compared the large-scale genetic data from the Ovarian Cancer Association Consortium with data on mutations that disrupt the genes in ovarian and other tissues. By putting these two pieces of information together, the researchers were able to identify 34 genes associated with an increased risk of developing ovarian cancer.
The study discovered that in women at greatest risk of ovarian cancer because of their genetic blueprint, “there is an interplay between their genetics and the specific genes that drive the very earliest stages of cancer development,” said Gayther. Ultimately, the findings may provide a basis for stratifying women based on their likelihood of developing the disease.
“One novelty of this work is that we looked at risk variants that operate through alternative splicing rather than just the total abundance of a gene, which led us to genes we would not have otherwise identified,” Gusev observes. “Beyond a better understanding, mechanisms that operate through splicing open up new drug-target opportunities.”
I had Genenectic blood work about 3 years ago. Was not classified as having the gene but was not %100.
My mom died of ovarian cancer at 52. I did brca1 and 2 and it’s negative. Will I be helpful in any clinical trial?
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I am very impressed with your latest research. I was diagnosed with stage 3 Ovarian Cancer in 2019. I am 72 years old. I am extremely thankful for all the research you are working on and all of your accomplishments.
Thank you for this!
I was diagnosed July 2018. In continued treatment at DF Londonderry. I feel great…. on Taxol and Avastin. We need earlier detection and better training for primary doctors. Mine was missed by two doctors.
I am absolutely thrilled to read this article about Ovarian CA I had my first back in 2004 and my second one in 2008 only to find out that my mother at 90 years of age tested to have the same BRCA 2 mutation. I was one of the people tested in the consortium
i’m glad that all of us could contribute to the advances in over here and cancer it’s tough going but Living is wonderful . Since 2001 I’ve had ovarian twice breast wants thyroid once and since 2010 been a multiple myeloma patient. so the more we do to help advances and studies the more people will live thank you ever so much
ELAINE. HORN RUBIN 2019
If 34 genes were identified to increase ovarian cancer risk, why isn’t it suggested for patients, especially high risk patients, to get genetic testing when they are young? That way, wouldn’t it make sense to catch it early and give the patient the choice to follow a preventative path if they so choose? I have been told that genetic testing is expensive. I believe it is more expensive to have a patient go through numerous surgeries, chemotherapy, medicines etc.
I have had ovarian cancer due to various mutations. I have the PALB2 gene. My daughter was gene tested and she also has this gene. Now I have three granddaughters and I am trying desperately for them NOT to go through the hell that ovarian cancer can cause. I ask all researchers, doctors & medical workers to please advocate for gene testing. Thank you for your time and energy in fighting this monster. We really appreciate all your hard work!❣️