CHEK2

CC2016

I just found this and am now so confused! I understood CHEK2 to be a gene mutation within an area of where cancer has been proven to be. All of our mutations may or may not be the same ones, that it's truly a gray area until researchers figure it out. And it's not even gauranteed to be related to cancer.

In my case, they ran an extended panel because of BC and other cancers in my extended family- I've got a small immediate family with just one case of cancer but when you go to my parent's aunts and cousins there were several. And I was diagnosed with cancer at 41, and my father at 37. I was preparing for a BMX if I came back BRCA+ but didn't. My geneticist said that it would be my decision ultimately, of course, but the BMX would not give me any different outcome with the research data they currently have. She even said that the mutation could be related to cancer or could be related to the shape of the eyebrows, there is just not enough data. Researchers are working on this whole gray area of mutations and some might be figured out in a month while some might take years. I'll be notified once mine is figured out, whenever that may be.

From what some of you are saying it sounds like CHEK2 has already been found to be cancer related and closely associated with BRCA. I'm so confused and will be so upset if I should have gone through a more aggressive surgery to begin with.

BarredOwl

Hi CC2016:

Please note that a number of the other people in this thread have known "pathogenic" mutations, so if your mutation is not a known "pathogenic" mutation, you may appropriately receive different medical advice.

I think you may have misunderstood the advice you received. CHEK2 is not known to be related with brow shape. The eyebrow reference may just be an example of the type of genetic variation (in another gene) that is not known to confer added risk.

Please review the content of your test report for what it says about the type of mutation you have, and discuss it again with your genetic counselor.

There are different types of mutations in the CHEK2 gene. Different mutations can have very different effects on risk profile. The different types of mutations in a gene can be classified into three general groups:

(1) "pathogenic variants" - These are known to be harmful and confer added risk of certain types of cancer(s);

Among the various known CHEK2 pathogenic variants, different variants may confer differing degrees of added risk. Even with the exact same pathogenic CHEK2 variant, it appears that the added lifetime risks for carriers may vary depending family history of breast cancer in first- and second-degree relatives.

(2) "neutral variants or polymorphism" - based on available data, these are not currently considered to confer added risk;

(3) "variants of unknown significance" or "VUS", also referred to as "variants of uncertain significance - These confer either: (a) no added risk; OR (b) some added risk of unknown magnitude. It is not known whether (a) or (b) is the true situation, but the VUS might be harmless.

You mentioned: "She even said that the mutation could be related to cancer or could be related to the shape of the eyebrows, there is just not enough data." You must confirm it with your providers, but this sounds a bit like option (3), a VUS, where there is not enough known about the particular mutation you have, and it is unknown at this time whether it could be harmful or just an ordinary and harmless genetic variation in the CHEK2 gene. Absent very, very significant family history, prophylactic surgeries are not typically recommended in the case of a VUS.

====> Do you know if the CHEK2 change you have is classified as a "pathogenic" mutation or is it another type, such as a neutral polymorphism or variant of unknown significance "VUS"?

Another point of clarification:

CHEK2 is a known cancer-related gene. It can sometimes be involved in (a) hereditary (inherited) cancer; and/or (b) it can be present in a tumor (not inherited, but due to an accidental mutation).

(a) A person can inherit a copy of CHEK2 with a mutation in it, so all of their cells contain the mutated copy (normal breast cells, tumor cells, blood cells, etc). Because it is in all their cells, their eggs or sperm may contain the mutated copy (50% chance for a single mutation), and it is "heritable". If you test their blood cells, you will find the CHEK2 mutation. If the mutation is "pathogenic," it can confer a genetic pre-disposition to (increased risk for) breast cancer.

(b) Some people who inherited two normal CHEK2 genes may have a mutation of CHEK2 only in their tumor cells. If you test their blood cells, you will only see normal copies of CHEK2. A mutation present only in tumor cells (but not other cells) is called a "somatic" mutation.

It sounds like you had a genetic blood test that identified a "heritable" CHEK2 variant. However, if it was actually the tumor tissue that was tested for CHEK2, please advise.

Please ask your genetic counselor which of the three types of mutations you have (pathogenic; neutral; or variant of unknown significance), and to explain again to you what is and is not known about it, and why prophylactic surgery is not being recommended in your specific case.

BarredOwl

CC2016

Okay, this makes more sense. Without looking at the paperwork I do remember the "unknown significance" part being a big part of the results. Whew. Just couldn't figure out how I misinterpreted so much but then hadn't heard about the other parts before. My unexpected summer school crash course on breast cancer is still going

mustlovepoodles

I had my BMX due to having a more aggressive PR- BC, plus two pathogenic gene mutations, not just the Chek2.

Molly50

CC2016, did you see a genetic counselor?

Christy86m

Hi - I was BRCA1, BRCA2 and BART negative in 2012. Although I have NO family history of breast or ovarian cancer, I was able to work with genetics on getting a 79 multi cancer panel approved by my insurance. I tested positive for Chek2 and two variants in Palb2 and Axin2. I had a bilateral mastectomy with no recon so don't need to have follow up mammograms or MRI's but will now have annual colonoscopies instead of every 3 years. I am a little worried about my variant at Palb2. HUGS!!!!

Christy86m

Wow - you lost me at hello but your reply is profoundly interesting. I am assuming you have your PhD in genetics I was just tested positive yesterday (Chek2) and have saved your thread to discuss with my geneticist. Just wow. Very informative. Thank you for taking the time to post this!!!! XO Christy Mattey

BarredOwl

Hi Christy86m:

I received genetic testing for BRCA1 and BRCA2 only, but I have not eliminated the possibility of further panel testing. I am a layperson with no medical training so, as you are planning to do, all information above should be confirmed with your genetic counselor or other medical genetics professional to ensure receipt of accurate, current, case-specific expert professional medical advice, in light of your personal medical and family history.

Be sure to request complete copies of your test results, with details regarding the particular change(s) identified and the specific definitions used by your test provider for classification (e.g., VUS, etc.)

Best,

BarredOwl