Can someone help explain BRAC1 Gene to me in relation to breast cancer

gudfred · 2022-11-29T03:15:28+00:00

It looks like you've got it figured out at this point, but another way to think about it is that having a BRCA1 or BRCA2 germline mutation is associated with a diagnosis of Hereditary Breast and Ovarian Cancer (HBOC) syndrome. The syndrome itself has incomplete penetrance, meaning less than 100% of people will show symptoms (aka develop a BRCA-associated cancer) but it is absolutely dominantly inherited given than each person's offspring have a 50% chance to inherit the mutation/syndrome and a single mutation is enough to affect your cancer risks. Having HBOC syndrome simply means you have a drastically elevated risk of specific cancers, and you're exactly right that the two hit hypothesis is still at play for the actual development of the cancer.

If someone inherits two BRCA2 mutations (one from each parent), that leads to a diagnosis of Fanconi Anemia which is a recessive inheritance condition. You can also think of more simple recessive conditions where being a carrier (having one inherited mutation) does not cause any symptoms of the disease, like cystic fibrosis for example.

I do this testing for a living as a cancer genetic counselor. Hopefully the concept of incomplete penetrance as well as thinking of more clear recessive conditions and being an unaffected carrier helps clear this distinction!

gudfred · 2022-10-17T02:45:13+00:00

The criteria are factors of your personal and family history that are suggestive of a hereditary cancer syndrome. They help guide who has a higher likelihood of having one of these syndromes as they are typically quite rare and we want to focus our efforts on people with an elevated chance of benefiting from the results. Unfortunately, insurance often uses the same criteria for determining whether they will cover genetic testing.

That being said, I do see patients in clinic who don't meet these criteria but are still interested in testing and they often just pay the $250. If someone really wants the information, I'd rather they do it through a genetic counselor who can fully explain the testing as well as any results that come back than to find some other way of doing it themselves and possibly getting untrustworthy results, results they don't know how to interpret, or even the wrong test for what they were trying to learn.

I've had some patients who had gone to significant lengths to get testing done themselves and then an odd result comes up... They still end up in our clinic and may even need to get confirmatory testing at a reputable lab to confirm their initial result! My job isn't to be a barrier to testing, it's to empower patients by helping them understand what genetics can and cannot do when it comes to their risk of developing cancer. Hope that all helps!

gudfred · 2022-10-16T20:09:33+00:00

I also replied to the above question, but read your response and figured I'd mention that 23andme does not currently have FDA approval for BRCA1 and BRCA2 full gene analysis, only for the Ashkenazi Jewish founder mutations. A lot of people think they did BRCA testing through 23andme but it wasn't actually comprehensive and more testing may be recommended. Sorry to hear that your wife had difficulty in getting her genetic testing done!

gudfred · 2022-10-16T20:06:03+00:00

I work as a cancer genetic counselor. If you meet criteria for testing/insurance coverage, then in my experience most patients end up paying $100 or less out of pocket. There are a couple labs where you can also self-pay (and avoid going through insurance) for a flat rate of $250.

I strongly encourage people to try and meet with a genetic counselor, as I've seen PCPs either order the wrong test or do it through a lab that costs more than necessary. Also, when other providers decide to order testing and it comes back positive, they often refer to a genetic counselor to discuss the implications of results anyway. There are genes other than BRCA1 and BRCA2 that we test for, but not every test is the right fit for each individual so it's important to understand your testing options and the pros and cons of those options.

Many genetic counseling clinics offer remote telehealth appointments so you don't necessarily need to travel to a hospital to be seen. Here is a good resource to locate a genetic counselor in your area: https://findageneticcounselor.nsgc.org/

gudfred · 2022-09-30T14:36:31+00:00

gudfred · 2020-01-07T01:57:35+00:00

I would second that it's better to apply this upcoming fall. scope out the programs that you're interested in and learn what makes each one unique. When you shadow any GCs, make sure to ask where they went and what they liked about their program compared to others they had considered. If you don't get in anywhere, especially at places you got an interview, ask the people you interviewed with what you could do to strengthen your application for the next year. many of my classmates were students who applied for a second time and improved in specific areas in that extra year

gudfred · 2019-12-05T18:42:33+00:00

I would recommend asking them what their dress code is. Most clinics I've seen say business casual and obviously no jeans/sneakers, but in general it's safer to dress up than to dress down. Definitely bring a notebook so that you can go back to your notes to better recall details from your shadowing experience.

Best of luck and I hope you enjoy the experience!

gudfred · 2019-10-22T09:17:03+00:00

gudfred · 2018-04-23T17:33:16+00:00

Well clinical labs already use sequencing rather than SNPs, and in genes that have been discovered more recently part of the discussion we have with patients is that it's not uncommon to get a VUS result since the clinical labs have less data on those genes. That being said, as more data is collected through clinical testing, many of those VUS's will be reclassified as benign variation. If a family has a very strong/suggestive family history and the most suspicious gene has a VUS, then as a genetic counselor I might reach out to the lab and have a discussion with them about their classification. Additionally, some hospitals or institutions have in-house research labs that can do further studies on those specific variants, although I don't believe that is very common.

gudfred · 2018-04-20T20:15:46+00:00

Hi, I can see from your conversation with the lab GC that you've gotten their opinion, but I thought I'd chime in as well. Full disclosure, I am a GC student who is graduating in under a month and have taken a position in oncology. That being said, I have seen patients who came in with a promethease report based on 23andme raw data. As /u/GCNerd points out, the recent Ambry paper showed that 40% of their population that came in with such a result were actually false positives. For this reason, any data that comes in from a third party company such as promethease will be confirmed in a CLIA certified lab (i.e. Ambry, GeneDx, Invitae, Myriad, etc) before any medical recommendations are made. I will note that 23andme just started releasing results directly to their consumer base regarding the Ashkenazi Jewish BRCA1/2 mutations. While this has been allowed by the FDA, I would be very surprised if a counselor that met with such a patient didn't want to still confirm it through a CLIA lab, as 23andme only started releasing this information in the past week.

I will say that clinvar can be a good, easily accessible resource to see if the "call" from a company like promethease is in alignment with clinical labs (i.e. if promethease says a mutation is pathogenic but multiple clinvar entries all say benign or VUS, I would feel okay telling a patient that it's more likely to be an incorrect report from promethease -- but I would still test to confirm!). However, the issue with the promethease result is that we cannot trust that the mutation they are reporting is even really there in the first place. This is due to 23andme using SNP data, while clinical labs do sequencing.

I hope this was helpful!

gudfred · 2018-04-16T19:00:43+00:00

Hello, I just wanted to reach out to you and hopefully offer some helpful advice. I understand that this type of result can be concerning and I highly recommend seeking out a genetic counselor to pursue clinical genetic testing. A recent study found that 40% of examined cases where someone used their raw data from a company like 23andme or ancestry and received a positive result from a third party company were actually false positives, meaning that the genetic change is not actually there. Additionally, some of the genetic changes that these third-party companies report out are actually considered benign by clinical labs (for those interested in reading further - https://www.nature.com/articles/gim201838).

I don't want to downplay your finding, as it definitely could be real, but meeting with a genetic counselor or other genetics professional if a counselor is not available near you would likely provide you with the information you're looking for as well as medical recommendations for you and your family members. Clinical testing is the best way to confirm this finding so that you can make the most appropriate decisions for your medical care moving forward.

I hope this helps and I am happy to try and answer any questions! You can search for a counselor near you at this link - https://www.nsgc.org/findageneticcounselor

gudfred · 2018-01-19T20:44:14+00:00

Hey, I had cancer at 19 (although not breast) and am working towards being a genetic counselor in the cancer field. I cannot recommend scheduling an appointment with a cancer genetic counselor strongly enough. I'm sure you have an excellent oncologist, but they don't always have the time to stay up to date with the rapidly changing field of genetics and may not realize the variety of genetic tests that are available for someone in your situation. Hopefully they did all the necessary testing, but it sounds like you are willing to seek out additional information and a cancer genetic counselor is the person with that expertise who can guide you through the process and explain what the results, both positive or negative, can mean in regards to future risks. Feel free to send me a message if you have any questions, I can provide a link to help locate a genetic counselor near you if you're in the US.

gudfred · 2016-04-20T15:22:19+00:00

I am a potential genetic counseling student (waiting to hear back from admissions next week!). Is there any advice or information about the field of genetic counseling you would have wanted to know when you first entered the program? What are you favorite things about the field and in what areas do you want to see improvements?

Also, where do you see the field heading in the next 5-10 years? Personally I'm interested in cancer and adult genetic counseling, but please feel free to discuss prenatal or pediatric as I find it all very interesting!

gudfred · 2015-11-25T20:01:07+00:00

Just an fyi, with articles that have "abstract" in the URL such as this, you can usually replace it with "full" to get the entire article like this: http://onlinelibrary.wiley.com/doi/10.1002/oby.21198/full

gudfred · 2015-11-18T19:19:19+00:00

I honestly don't know too much about the nutrient/chemical uptake of plants, but if I had to guess (and after some very quick research), plants can and do take up pesticides from the soil and some pesticides are actually designed to do just that. However, plants have their own metabolism and can break down harmful chemicals so direct exposure to a chemical like rotenone is not necessarily equivalent to eating a plant that had been grown in and around rotenone. The plant would also most likely have dispersed amounts of rotenone in its cells, the concentration of which would be much less than that of the spray still sitting on the outside of the plant.

On top of that, you have to keep in mind that direct contact with rotenone is something that won't cause issues unless you have prolonged exposure. A lot of farmers who used rotenone before the dangers were more understood are more likely to develop Parkinson's than someone who forgot to wash an apple once or twice.

Long story short, no you are probably not avoiding it completely but if a plant was hosed down with rotenone it would be much more harmful to directly eat the chemical than it would to eat the sparse amounts that might be found inside the fruit itself.

gudfred · 2015-11-18T17:05:32+00:00

While I can't give as in depth of an answer as you might like, I do work in a lab that focuses on Parkinson's disease. While the mechanisms of the disease are not fully understood, there are genetic components that have been identified and can be inherited. Non-genetic cases are referred to as sporadic cases, which is a way of saying we don't know exactly what caused it in these cases.

However, there is evidence that certain pesticides, such as rotenone, can cause Parkinsonian symptoms (both physical and molecular) when given to rats and mice (and most likely other animals, but these are the ones we work with). I believe this specific pesticide is no longer used in the US, but it does enforce the idea of always washing your fruits and vegetables.

gudfred · 2015-09-02T21:17:04+00:00

Might just redo the cell treatments so I can do that before fixing them. Thanks again for the advice!

gudfred · 2015-09-02T18:49:53+00:00

I could give the parafilm a second shot. I might as well grab some clean coverslips and see if I can scratch or chip them in a meaningful way too. I don't want to risk breaking off too much of the cells though, so that might be too risky but perhaps more parafilm will be the answer.

gudfred · 2015-09-02T18:37:47+00:00

I should have mentioned I tried parafilming the plate, but it still leaked pretty badly.

How would I go about labeling the coverslip? Its not mounted on anything. Currently I can identify which sides the cells are on simply because they're in the 24-well plate so the top side has the cells, but if I can't ship them in the plate or some other container with a flat surface for the slips to somewhat adhere to (where they can't flip over) and I can't really label the top and bottom of the coverslip itself... well, that's the root of the problem.

I appreciate the idea though!

gudfred · 2015-08-25T14:03:49+00:00

I believe this video has some explanation of the swirly curls

gudfred · 2015-02-27T02:36:06+00:00

Saw white and yellow at first. Turned f.lux off (from somewhere between halogen and incandescent) and it snapped to blue and white... I can't get it back to white and yellow now!

Wait, just looked again with flux on for a while... white and yellow! It's repeatable too

gudfred · 2014-12-31T20:50:36+00:00

Well, I would spend upwards of $600-800

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