BRCA 1 and BRCA 2: Knowing Your Risk and Screening Options

Thursday, February 27, 2014 2:50 PM comments (0)

geneticsPeter Hulick, MD, MMsc, Medical Geneticist at NorthShore, discusses the increased risk for breast and ovarian cancer in women who carry the BRCA1 and BRCA2 gene mutation. He responds to the recent study from the Journal of Clinical Oncology on the impacts these mutations have on women as well as identifies ways women can minimize their risk.

What are your general impressions of the new study? 
The study, particularly given its size, helps further parse out the details of risk differences between BRCA1 and BRCA2.  There have been retrospective studies that have suggested this, but here we have a prospective study that adds further evidence.  In addition, it looks at overall reduction in mortality which shows the gains go beyond the ovarian cancer risk reduction.

Who is most at risk for having the BRCA1 and BRCA2 mutation?  
There are many potential ways someone can be at risk, but certain characteristics stand out:

  1. Anyone of Ashkenazi Jewish descent who has personal history of breast cancer or a personal history of ovarian cancer
  2. Anyone diagnosed with breast cancer at age 45 or younger
  3. Anyone diagnosed with ovarian cancer at any age

Ultimately, if you have been diagnosed with breast and or ovarian cancer, or multiple family members have, you should discuss the family history with a cancer risk specialist.

What is the difference between the two genes?  
Both genes are involved in how the body repairs DNA damage that accumulates and maintaining the “checks and balances” that control cell growth.  As this study reinforces, there are differences in cancer risks associated with each.  While the risk for ovarian and breast cancer might be somewhat lower for BRCA2 than BRCA1 (though still considered high compared to average risk), BRCA2 mutation carriers tend to have higher risk for other BRCA-related cancers (e.g. pancreatic, prostate).

What preventative measures can women engage in to minimize their risk of breast and ovarian cancer?  
The first step is to get an accurate assessment of one’s risk.  Women may still be at elevated risk even if BRCA testing is negative.  Other genes and non-genetic factors contribute to ovarian and breast cancer risk.  Depending on the risk level, certain options exist for increased screening, preventative medications or preventative risk-reducing surgery.  This is a complex and very personal decision and accurate information about risk is key.

What screening options are available for women to learn more about their risk? 
The first thing women can do is to get an accurate family history from BOTH sides of the family, then discuss with one’s physician.

What next steps would you recommend for women with the BRCA1 / BRCA2 mutation? 
I would recommend women talk to their doctors about speaking to someone familiar with cancer genetics such as a geneticist, a genetics counselor, or a gynecologist/oncologist/breast surgeon knowledgeable about the management of BRCA carriers.  There are online resources from Be Bright Pink and FORCE that can be helpful in understanding the implications of having BRCA mutation and putting in a plan to reduce risk.  As this study and others have shown, we have the ability to greatly reduce one’s risk if we know one faces these risks.

Parkinson's Disease: Genetic Risk Factors, Family History and Research

Thursday, April 04, 2013 11:47 AM comments (0)

April is National Parkinson’s Disease Awareness Month. All this month, we will feature a series of posts addressing Parkinson’s disease symptoms, genetics, treatment options and more from NorthShore neurologists—Demetrius Maraganore, MD, Aikaterini Markopoulou, MD, and Ashvini Premkumar, MD— to raise awareness about this common and often disabling neurological disorder.

by Demetrius Maraganore, MD:


laboratoryAre the children of a parent with Parkinson’s disease likely to inherit the disease? Is there a greater risk if the father or the mother has the disease?

My research team conducted family studies that defined the risk of inheriting Parkinson’s disease. The children of Parkinson’s disease patients carry a two-fold risk for Parkinson’s disease. They are twice as likely to get Parkinson’s disease compared to the children of persons without Parkinson’s disease. However, one needs to consider that the lifetime risk for Parkinson’s disease in the general population is 2%, so the risk of Parkinson’s disease for the children of a patient is 4%, or twice the baseline risk for the general population. That’s a pretty low risk and I wouldn't recommend any specific lifestyle changes or preventive therapies for the children of patients with Parkinson’s disease.
 
That said, about 5% of Parkinson’s disease cases are due to an inherited gene abnormality (mutation). In families where multiple members have Parkinson’s disease, the risk may be as great as 50% to the children of an affected person. When there are multiple family members with Parkinson’s disease, I refer patients for genetic counseling and in some instances we also perform genetic testing. 

What are the most important genetic risk factors for Parkinson’s disease?

There are two types of genetic factors that are important to Parkinson’s disease: 1) genes that rarely cause familial Parkinson’s disease (multiple affected members in the same kindred), and 2) genes that are not causal but that slightly increase the risk for Parkinson’s disease in populations worldwide (susceptibility genes). About a dozen genes have been identified as rare causes of familial Parkinson’s disease, and about a dozen genes have been identified as common risk factors in populations worldwide. The causal gene mutations are rare, accounting for less than 5% of all Parkinson’s disease cases. The susceptibility gene variants are common—e.g., occurring in 25% of persons in the general population—but they have small effects (no more than doubling the risk for Parkinson’s disease). 

Of all of the Parkinson’s disease genes, the most important is alpha-synuclein because it is both a causal gene in some families and also a susceptibility gene in populations worldwide. In other words, rare variants (mutations) cause Parkinson’s disease in rare families, while common variations (polymorphisms) increase the risk for Parkinson’s disease worldwide.

The alpha-synuclein gene holds the code for making the protein alpha-synuclein. The protein alpha-synuclein accumulates abnormally in the brain cells of every patient with Parkinson’s disease regardless of the causes. Many scientists believe that it holds the key to understanding and curing Parkinson’s disease. Our research team at NorthShore has led many of the most important studies of alpha-synuclein and Parkinson’s disease, including studies in families and in populations worldwide. We were also amongst the first to study the interaction of alpha-synuclein with other genes or environmental factors, or to study the association of the alpha-synuclein gene with motor and cognitive outcomes in Parkinson’s disease. 

Are there genetic research studies of Parkinson’s disease at NorthShore? How can I participate?

At NorthShore we are conducting a genetic study called the DodoNA Project. We aim to discover genetic factors that predict how neurological diseases progress in severity and that predict disease outcomes. We aim to use this information to individualize the care of our patients and to halt the progression of neurological diseases. One of the diseases we are studying is Parkinson’s disease. 

We will enroll at least 1,000 Parkinson’s disease patients into the study, and follow them at least annually for several years. To be eligible for the study you need to be new to our Movement Disorders practice within the past year, a resident of Cook or Lake County and willing to provide a blood sample for DNA extraction and storage. We also require your permission to compare your genetic code with the information that we collect in your medical record.

If you wish to participate, the best thing to do is to request an appointment to be seen as a patient in the Department of Neurology at NorthShore. We can then enroll you into the study after your office visit. You can also support the DodoNA project by joining forces with NorthShore’s Auxiliary and by supporting the Hospitals’ Gala

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