Day 22 A Month of Teal: Gene Mutations and Ovarian Cancer

Most ovarian cancers are sporadic. They are caused by somatic mutations.

But about 20 to 25 percent of women diagnosed with ovarian cancer have a hereditary tendency to develop the disease. This tendency is called Hereditary Breast and Ovarian Cancer Syndrome (HBOC). HBOC may be diagnosed if your family history shows multiple members of the same side of your family being diagnosed with breast and/or ovarian cancer.
Cancer.net lists these situations as indicative of HBOC

• 1 or more women are diagnosed at age 45 or younger
  
• 1 or more women are diagnosed with breast cancer before age 50 with additional family history of cancer, such as prostate cancer, melanoma, and pancreatic cancer
  
• There are breast and/or ovarian cancers in multiple generations on the same side of the family, such as having both a grandmother and an aunt on the father’s side both diagnosed with these cancers
  
• A woman is diagnosed with a second breast cancer in the same or the other breast or has both breast and ovarian cancers
  
• A male relative is diagnosed with breast cancer
  
• There is a history of breast cancer, ovarian cancer and/or pancreatic cancer on the same side of the family
  
• There is a history of breast and/or ovarian, pancreatic, or male breast cancer in a family of Ashkenazi Jewish ancestry
  

What germline mutations are linked to Hereditary Ovarian Cancer?
"Between 65 and 85 percent of germline mutations are in the BRCA1 or BRCA2 gene. The lifetime risk of ovarian cancer in women with a BRCA1 gene mutation is 40 to 60 percent, and the lifetime risk in women with a BRCA2 gene mutation is 20 to 35 percent."

"A significantly increased risk of ovarian cancer is also a feature of certain rare genetic syndromes, including a disorder called Lynch syndrome. Lynch syndrome is most often associated with mutations in the MLH1 or MSH2 gene and accounts for between 10 and 15 percent of hereditary ovarian cancers."

Are there other mutations linked to  ovarian cancer? 
Yes, other mutations  include:

• AKT1
• BARD1
• BRCA1
• BRCA2
• BRIP1
• CDH1
• CHEK2
• CTNNB1
• MLH1
• MRE11
• MSH2
• MSH6
• NBN
• OPCML
• PALB2
• PIK3CA
• PMS2
• PRKN
• RAD50
• RAD51C
• RAD51D
• STK11
• TP53 Li-Fraumeni Syndrome (LFS)

Source:NIH  https://ghr.nlm.nih.gov/condition/ovarian-cancer#genes  

It is recommended by the Society of Gynecologic Oncology that all women diagnosed with ovarian cancer have genetic testing. (https://www.sgo.org/wp-content/uploads/2012/09/PB-182.pdf)
The SGO also has available a Genetics Toolkit 2016  online.

Additional information on HBOC may be found on the FORCE website http://www.facingourrisk.org/index.php 

My next post for Ovarian Cancer Awareness Month will be on Monday Sept 25th. 

Dee
Every Day is a Blessing! 

What Are the Risk Factors For Ovarian Cancer

--> Before I list the risk factors for ovarian cancer it is important to know that having a risk factor does not mean you will get the disease. But there are some factors that have been found to increase the likelihood that a women will develop the epithelial ovarian cancer ( the most common type). 

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The average woman’s risk for ovarian cancer in her lifetime is 

1 in 75.

Risk Factors:

Age: The average age of women diagnosed with ovarian cancer is 63 years.

Obesity: Studies have shown a relationship between obesity and ovarian cancer (BMI  of 30)

Reproductive History: Never being pregnant

Estrogen Therapy: Studies show that taking estrogen 5-10 years have an increased risk

Male Hormones: Studies show that women who take male hormones are at a higher risk for Ovarian cancer.

Personal History: Women who have had breast , uterine, colon or rectal cancer have an increase risk for ovarian cancer.

Family History:A family history of breast, ovarian, colorectal cancer ( BRCA1and BRCA2 gene mutations, Lynch syndrome, hereditary nonpolyposis colorectal cancer)  

PTEN Syndrome: Women with the inherited mutation of the PTEN gene have an increased risk of ovarian cancer. Also known as Cowden disease .

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Fertility Drugs: Some studies showed that the use of fertility drug Clomid , increased a woman’s risk for ovarian cancer.

Talc: Women who use talcum powder in the genital area have an increase risk. Please note that since the 70’s talc powder products must be asbestos-free. 

For more information please check this NCI source : http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-risk-factors

Dee
Every Day is a Blessing ! 

Research News: Gene mutations, stem cells

Same Mutations in 12 Different Cancers

An article titled

Mutational landscape and significance across 12 major cancer types

appeared in the journal Nature. Researchers at the Washington University in St Louis analyzed data from the The Cancer Genome Project. They  looked at over 3200 tumors in 12 different cancers. They were looking at mutations and insertions/deletions in "breast adenocarcinoma (BRCA), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), uterine corpus endometrial carcinoma (UCEC), glioblastoma multiforme (GBM), head and neck squamous cell carcinoma (HNSC), colon and rectal carcinoma (COAD, READ), bladder urothelial carcinoma (BLCA), kidney renal clear cell carcinoma (KIRC), ovarian serous carcinoma (OV) and acute myeloid leukaemia (LAML; conventionally called AML)  "

In those cancers they noted 127 significantly mutated genes(SMGs) . They found that that TP53 mutation played a roll in serous ovarian cancer , breast and head and neck cancers and feel that a common treatments strategies could be used for these cancers.

Source: Nature
WSJ article  

Ovarian Cancer Stem Cells in Mice

The Cornell Daily Sun recently published the article


Cornell Researchers Find Possible Origin of Ovarian Cancer


about the research of Dr. Alexander Nikitin, professor of pathology. In his research, Dr Nikitin found stem cells in the hilum of mice. "Many other cancers, such as stomach and cervical cancer, are known to originate in junctions between the layers of tissue that cover the organ, according to Nikitin" The hilum is an area found between the epithelial cells on the surface of the ovary and the mesothelium cells found inside layers of the ovary. He took these stem cells along with differentiated ovarian cells and inactivated the tumor suppressor genes. He then injected the cells into  health mice.  The stem cells grew aggressive tumors while the ovarian cells grew tumors infrequently. Dr Nikitin is now looking for stem cells in the same region of the ovaries in humans.

Source: The Cornell Daily Sun 

Dee
Every Day is a Blessing!

OC awareness month #18 - Lynch Syndrome

While at the ASCO meeting in June I spent some time talking to the Myriad representatives. Myriad is the company that does the genetic testing for gene mutations, deletions and additions. I asked if the test used today is any different from the one they used to test my blood  6 years ago. There response was that they would test for LYNCH SYNDROME.

I knew Lynch syndrome associated with colorectal cancer but I wasn't sure how strong a connection there was between Lynch Syndrome and  ovarian cancer.

"Lynch Syndrome is also known as hereditary non-polyposis colorectal cancer (HNPCC), is a type of inherited cancer of the digestive tract. Lynch syndrome increases a woman's risk of ovarian and uterine cancer. It is caused by mutations in several different genes. Lynch syndrome also increases the risk of colorectal cancer, as well as cancers of thestomach, small intestine, liver, bile duct, urinary tract, the brain and central nervous system, and possibly breast cancer. http://www.cancer.net/all-about-cancer/genetics/genetics-ovarian-cancer
"
Mutations in the MLH1 or MSH2, MSH6 or PMS2 or EPCAM genes  are associated with Lynch Syndrome. Families with Lynch syndrome have two or more members who have colorectal, endometrial , ovarian or other cancer.

For more information about the test for Lynch Syndrome see this page.

Here is some interesting research on the Lynch Syndrome Ovarian Cancer link.

* Ovarian cancer linked to Lynch syndrome typically presents as early-onset, non-serous epithelial tumors.

*Routine Lynch Syndrome Screening Varies at U.S. Cancer Centers

* The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer.



Dee
Every Day is a Blessing!