Certain genetic mutations (or changes) in DNA can lead to uncontrolled cell growth, which we know to be cancer. If these mutations are found in germ cells of either parent (i.e., sperm or egg cell), there is a chance that the child may carry the same mutation that puts them at a higher-than-normal risk for developing that cancer. 

Hereditary cancer syndromes refer to inheritable genetic mutations that are passed down across generations and put one at a higher risk for developing certain cancers. There are two types of hereditary cancer syndromes and genetic mutations that can significantly impact one’s risk for developing gynecologic cancers– BRCA Mutation(s) and Lynch Syndrome. 

What is BRCA? 

BRCA stands for BReast CAncer gene. BRCA1 and BRCA2 are two genes involved in repairing damaged DNA. When these genes are mutated, damaged and potentially cancer-causing mutations can go undetected. 

As indicated by its name, BRCA is infamously known for causing an aggressive form of (triple-negative) breast cancer to run in families. However, many people don’t know that BRCA mutations can also increase family members’ risk of developing other cancers such as prostate and ovarian cancer.  

According to the National Institute of Health, approximately 1.2% of the genetic population will develop ovarian cancer. On the other hand, those with a harmful BRCA1 mutation are at a 39-44% risk of developing ovarian cancer, particularly the most lethal type– High-Grade Serous Ovarian Cancer (HGSOC). The risk is 11-17% for those with a harmful BRCA2 mutation. Thus, having a family history of BRCA-associated breast cancer can also put you at a higher-than-normal risk for developing ovarian cancer. 

What is Lynch Syndrome? 

Lynch Syndrome is another inheritable cancer syndrome that accounts for faulty DNA repair mechanisms. Lynch Syndrome is also called “Hereditary Non-Polyposis Colorectal Cancer” (HNPCC) as it has been associated with a genetic predisposition for early onset colon and rectum (prior to the age of 50).  

With regards to gynecologic cancers, Lynch Syndrome has also been found to put individuals at a higher risk for endometrial (uterine) and ovarian cancer. A study by the University of Texas has found that those with Lynch Syndrome are at a 40-60% risk of developing endometrial cancer and 12% risk for ovarian cancer. 

Other Inheritable Cancer Genetic Mutations

Aside from BRCA mutations and Lynch Syndrome, there are several other inheritable genetic mutations that can put you at risk for certain gynecologic cancers. For instance, BRIP1 is associated with an increased risk for ovarian and breast cancer. As for RAD51C and RAD51D, mutations in these genes are associated with a genetic predisposition for endometrial, intestinal, ovarian cancer, and cancers of the urinary tract. 

Genetic Testing for Early Detection and Intervention

Genetic testing and counseling can help people estimate their genetic risk for developing certain cancers within their lifetime. It also provides you with information on how genetic conditions may affect you or your family. Genetic testing is often recommended for those who have had certain cancers (i.e., breast, ovarian, endometrial, colorectal, etc.) or exhibit a pattern of cancers within their family tree.  

Genetic testing may not only benefit you, but also your immediate and extended family members. The earlier you identify genetic predispositions, the timelier you and your healthcare provider can monitor your health. Early knowledge may also allow you to make timely decisions such as considering risk-reducing procedures or fertility preservation. 

Genetics is a powerful prognostic tool in the gynecologic cancer space. Although not everyone who has a family history or genetic mutation is guaranteed to develop cancer, knowing your risk gives you the time and opportunity to think carefully about your health and future. Making the appropriate lifestyle changes and medical decisions may help mitigate your genetic risk for developing cancer. In the end, genetic testing seeks to put the power back in your hands so that you and your family can take the reigns over your health. 

Our Work with Hereditary Cancer Syndromes

Several researchers at the Gynecologic Cancer Initiative (GCI) recognize the potential for genetic testing to save lives and are actively working to create better care for those with hereditary cancer syndromes. Some of the researchers doing work in this area include:  

Dr. Lesa Dawson

Dr. Lesa Dawson is a gynecologic oncologist and adjunct professor at the University of British Columbia. Her research focuses on gynecologic cancer prevention and survivorship for families with Lynch Syndrome, BRCA mutations, and other genetic predispositions. Dr. Dawson’s past work has included the establishment of the Inherited Gynecologic Cancer Screening & Prevention Clinic in St. Johns, NL in 2002 and a recent partnership with Prementum Health to develop a cancer risk assessment and prevention service.  

Last year, Dr. Lesa Dawson worked with the Gynecologic Cancer Initiative and UBC Department of Obstetrics and Gynecology to open the Gynecologic Oncology & Survivorship Clinic at Vancouver General Hospital. The clinic was launched in partnership with BC Cancer’s Hereditary Cancer Program to serve women with hereditary gynecologic cancer mutations or family history concerns. Their services include post-surgical menopause management, preventative surgical decision support, and access to the latest research and clinical trials. 

Dr. Janice Kwon

Dr. Janice Kwon is a gynecologic oncologist, Associate Head, and professor at the Department of Obstetrics and Gynecology at the University of British Columbia. She is also the Chair of the Gynecology Surgical Tumor and acting Chair for the Priority and Evaluations Committee at BC Cancer. Among her many accomplishments, Dr. Kwon is also Chair of the National BRCA Collaborative through the Society of Gynecologic Oncology of Canada. 

Dr. Kwon’s research currently focuses on health policy regarding gynecologic cancers and hereditary cancer syndromes. She is also currently investigating the cost-effectiveness of genetic testing criteria and risk-reducing strategies for those at risk for genetic mutations. 

Women diagnosed with High-Grade Serous Ovarian Cancer have a 20% chance of carrying the BRCA mutation and is eligible for genetic testing in BC. However, only 50% of those with HGSOC follow through with genetic testing. Thus, Dr. Kwon is currently looking at the cost and benefits of using tumor testing to determine whether a patient has a harmful BRCA variant and has the potential to pass it onto their children. This proposed strategy has the potential to help reserve genetic testing and counseling resources only for those who are most at risk of carrying genetic cancer mutations. 

The GCI recognizes cancer genetics and hereditary cancer syndromes as major areas to be explored further as to enhance the early detection, intervention, and survivorship from gynecologic cancers.