Showing posts with label genetics. Show all posts
Showing posts with label genetics. Show all posts

Tuesday, September 5, 2017

Day 5: A Month of Teal - Ovarian Cancer Risk Factors

1 in 75 women develop ovarian cancer 

Risk factors for epithelial ovarian cancer ( the most common type) include: 
  • Increased Age 
  • Genetics :  BRCA 1 or 2 Mutation, Lynch Syndrome, Peutz-Jeghers syndrome, Nevoid basal cell carcinoma syndrome, Li-Fraumeni and Ataxia-Telangiectasia (http://www.cancer.net/cancer-types/ovarian-fallopian-tube-and-peritoneal-cancer/risk-factors-and-prevention )
  • A family history of epithelial ovarian cancer, fallopian tube cancer, peritoneal cancer, premenopausal breast cancer and/or male breast cancer
  • Endometriosis
  • Being of Ashkenazi Jewish heritage
  • Being post menopausal
  • Infertility, never having children
  • Obesity
  • Using menopausal hormone therapy
For more information please see:
https://ocrfa.org/patients/about-ovarian-cancer/risk-factors/ 
http://www.cancer.net/cancer-types/ovarian-fallopian-tube-and-peritoneal-cancer/risk-factors-and-prevention


Dee
Every Day is a Blessing! 



Monday, January 11, 2016

More than just BRCA1 & 2

Most women diagnosed with ovarian cancer have heard of the link between germline mutations in the BRCA 1 & 2 genes and ovarian cancer. The Society of Gynecologic Oncology recommends that all women diagnosed with ovarian cancer have genetic testing for those mutations. Studies have also found that Lynch Syndrome ( formerly known as “hereditary nonpolyposis colorectal cancer” (HNPCC) ) places a women at increased risk for ovarian cancer. I wrote about these germline mutations in a blog post in September 2015.

On December 30, 2015 JAMA Oncology journal published the article

Inherited Mutations in Women With Ovarian Carcinoma


This study of 1915 women looked at the importance and prevelance of other germline ( passed from parent to child) mutations associated with ovarian cancer.

They found that 18% of the women studied carried
"pathogenic germline mutations in genes associated with OC risk. PALB2 and BARD1 are suspected OC genes and together with established OC genes (BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, and MSH6)"

So we now have 11 genes suspected of causing hereditary ovarian cancer. (Since the article is behind a paywall I could not access the complete study.) A commentary on that research can be found here. The commentary raises the issue that the mutations to BRIP1, RAD51C, RAD51D  and BARD1 have not been well characterized and have uncertain clinical use at this time when compared to BRCA 1 & 2. 

The commentary states that investigators should look at "different paradigms for identifying key new factors and mechanisms underlying OC risk" I look forward to those studies.

Dee
Every Day is a Blessing! 
 


Additional Sources:
Ovarian Cancer Risk and Prevention
http://www.cancer.net/cancer-types/ovarian-cancer/risk-factors-and-prevention
Lynch Syndrome
http://www.cancer.net/cancer-types/lynch-syndrome
Hereditary Breast and Ovarian Cancer
http://www.cancer.net/cancer-types/hereditary-breast-and-ovarian-cancer

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. (http://www.cancer.net/cancer-types/lynch-syndrome)

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. (https://www.sgo.org/clinical-practice/guidelines/genetic-testing-for-ovarian-cancer/ ) 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. ( http://www.asco.org/press-center/asco-releases-updated-policy-statement-genetic-and-genomic-testing-cancer ) 

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. 


Dee
Every Day is a Blessing! 

Additional Sources:

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

Wednesday, May 21, 2014

2014 Annual Retreat on Cancer Research In NJ: Public Forum Personalized Cancer Therapy

For the past few years, I have attended Public Forums that are part of the Annual Retreat on Cancer Research in NJ. Today's forum on Personalized Cancer Therapy held a special interest for me.

I have always wondered how my cancer was different from other women who were diagnosed with Stage 3 serous papillary epithelial ovarian cancer (high grade). Why did my tumors respond so well to chemotherapy treatments? Why was I able to go into remission for a second time for a longer period of time than my first remission?  Well, there are researchers in NJ who are asking the same questions. They are looking beyond the organ and histology but looking at the genetics of tumors. 

You may recall that last year I was asked to participate in a clincial trial in which tumor tissue from my initial diagnosis and my recurrence well as my blood would undergo genetic sequencing.  I learned a bit more about that process today at the public forum. 

Dr. Shrindar Ganesan, Rutgers Cancer Institute of NJ ( RCINJ),  and the lead investigator of the trial I participated, in welcomed everyone to the forum. He explained that genome sequencing is generating a large amount of information and what must now be done is to transfer that into useful knowledge for patients. He also said that each patient has a unique response to treatment be it chemotherapy, immunotherapy or targeted therapy. He then went on to introduce each of the other speakers. 

Dr. Kim Hirshfield ( RCINJ ) began "Next-Generation Sequencing for Every Generation:Everything you Need to Know but Didn't Know to Ask"  by telling us that "one size fits all" in cancer treatment does not work due to differences in individuals and tumors. She went on to explain about chromosomes, genes and how proteins are involved in the growth, proliferation , death and movement of cells. She described oncogenes and tumor suppressor genes and how they can cause cancer. There are also different type of mutations: germline mutations which are mutations you are born with and  somatic mutations those which are acquired later in life. 

Dr Hirshfield then went on to describe the Precision Medicine Initiative in which researchers are trying to understand the biology and mutations of tumor cells in order to offer patients the best treatment. Tumor samples are evaluated for 236 genes. The data from the evaluation is presented to a Molecular Tumor Board which helps determine the treatment. So far 100 patients have taken part in the Initiative. Twenty percent have been prescribed treatment based on their evaluation, another 20 percent have treatment plants but have not yet been prescribed the treatment due to the fact that they are stable or are in remission at this time. For the remainder of the patients some are no longer participating in the study for various reasons and for some there are no current drugs or trial drugs available for their specific mutations. In the 100 patient tumor samples tested there was an average of 3.6 mutations. 

Hetal Vig, a genetic counselor at RCINJ, presented "Capturing the Spectrum of Hereditary Cancers:A Moving Target in the Setting of Targeted Therapy.  She spoke about family pedigrees and germline mutations. Women with BRCA1 mutation have a 60% risk of developing ovarian cancer while those with the BRCA2 mutation have a 25% risk of developing ovarian cancer. She then went on to mention Li-Fraumeni Syndrome ( I had not heard about this syndrome before and will have to look into it further.) This syndrome is linked to the p53 mutation. Hetal also said that all cancers are genetic but not all cancer is hereditary.  

Although the last speaker, Dr Janice Mehnert (RCINJ), spoke mainly about melanoma I found her presentation very exciting because of the progress that has made in less than 10 years in Melanoma treatments. In 2006 there was no good treatment for melanoma. Then they found that they could target the BRAF and MEK genes with some success (Vemurafenib). There has also been success with immunotherapy by targeting the PD1 and PDL1 genes. It may be possible to use targeted therapy and immunotherapy together but clinical trials are needed since more targets may translate into the treatment being more toxic to the patient.  Dr Mehnert then said that "Your tumor is your life" and the focus should be on the understanding each patients tumor. 

During the question and answer period I learned that:
The more suppressed the immune system the more cancer.
When using immunotherapy there may be an increase in tumor size due to inflammation but if the therapy is effective subsequent shrinkage will  occur. 
The researchers agreed that more advocates are needed to raise awareness of the importance of participation in clinical trials.  

I am so pleased to see such important research being done right here in NJ. I also urge my readers to consider participation in a clinical trial. It is through clinical trials that the knowledge we need to better understand how to target our individual cancers can be found. 

Dee
Ever Day is a Blessing!