Thursday, September 24, 2015

An Introduction to Genetics and Ovarian Cancer

When I was diagnosed with ovarian cancer I decided to learn as much as I could about the disease. While I was in treatment I was offered genetic testing for BRCA1 and 2 which I accepted. Our knowledge about the genetics of ovarian cancer has grown tremendously over the past ten years.

Let's start with this basic video from the NCI on genetics and cancer. 

Now let's talk about ovarian cancer in particular. 

About 15% of the ovarian cancers diagnosed are due to germline (inherited and passed on to offspring)  mutations in the BRCA1 and BRCA2 genes. Having these mutations increases the risk of ovarian cancer by 15-50%. “Nearly one-third of women with hereditary ovarian carcinoma have no close relatives with cancer, and 35% of women with hereditary ovarian carcinoma are older than 60 years at diagnosis”( NCI) .  The remaining ovarian cancers are due to what we call sporadic or somatic mutations. 

Following the BRCA mutations the next inherited syndrome that leads to ovarian cancer is Lynch Syndrome.  Mutations in the MLH1, MSH2, MSH6, PMS2 and EPCAM genes are linked to Lynch Syndrome.  Women who have Lynch syndrome have an estimated 9-12 % lifetime risk for developing ovarian cancer. (

In June 2011, the The Cancer Genome Atlas (TCGA) Research Network issued the results of whole-exome sequencing of ovarian cancer tumors. They examinesd the protein-coding regions of the genome, of 316 ovarian cancer tumors. 

The study found :

21 percent of the tumors studied showed mutations in BRCA1 and BRCA2 

six other statistically recurrently mutated genes: RB1, NF1, FAT3, CSMD3, GABRA6 and CDK12. CDK12 is involved in RNA splicing regulation 

96% of ovarian cancers had a T53 mutation. T53 controls a tumor suppressor protein that stops cancer from forming

108 genes were associated with poor survival

85 genes were associated with better survival

68 genes that could be targeted by existing Food and Drug Administration-approved or experimental therapeutic compounds 

Four related subtypes of ovarian cancer based on the patterns of DNA methylation—a chemical reaction in which a small molecule called a methyl group is added to DNA, changing the activity of individual genes. 

The SGO released a Clinical Practice statement in 2014 stating that all women diagnosed with ovarian, tubal and primary peritoneal cancer regardless of age or family history should receive counseling and offered a genetic test. ( ) Knowing a women has a BRCA mutation may allow her to receive PARP inhibitor treatment . Olaparib was recently approved by the FDA to treat women with recurrent ovarian cancer. 

In August  ASCO issued an updated policy statement on genetic and genomic testing. (

The more researchers understand the genetics of ovarian cancer the better they can  develop drugs to treat specific mutations and the more personalized women's treatment can become. 

Every Day is a Blessing! 

Additional Sources:

Lynch Syndrome and Ovarian Cancer
I Have Lynch Syndrome
 Ovarian Cancer : The Choice to Be BRCA Tested

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