Part VI: My Gremlin Genes

I'm struggling with how to explain something I don't really understand myself.  Thus, I will give you the broad strokes.  And the science nerds among you can fill in the gaps or tell me where I have it wrong.  

I have a STRONG family history of breast cancer.  Just over 20 years ago, my mom died from breast cancer.  Also, my maternal grandmother and my mom's two sisters had breast cancer.  About 6 weeks ago, I was diagnosed with breast cancer.  And just last week, my cousin (daughter of my mom's brother) was diagnosed with breast cancer.  

Even before knowing it was a thing people did proactively, I wanted to be rid of these cancer-prone breasts as soon as I was finished nursing babies.  But without a diagnosis, I am not sure many insurance companies want to pay for that and it seemed a bit extreme without having more information.  So, a few years ago, I met with a genetic counselor to discuss my family history and possible genetic testing.  At the time, the breast cancer family tree *only* included my mom, granny and one aunt.  My takeaway from that conversation was that our family did not fit the profile for a family with a BRCA mutation: no ovarian cancer and not all were diagnosed very young.  At the time, the BRCA mutations were the only "breast cancer genes" the tests would have looked at.  While I figured I would still do genetic testing at some point, the pressure was off.  It seemed unlikely they would find anything of use and I would still need to live life carefully and with the anxiety of if/when.

For the first time in my life, my procrastination paid off (sort of)!!  While I was procrastinating, the scientists were hard at work.  They identified some new genes to look at when conducting breast cancer-related genetic testing.  After my diagnosis in late October, I was tested and, as I expected, the results were BRCA negative.  However, "one variant of unknown significance was detected in the ATM gene".  The report also said, "[g]enetic testing for variants of unkown significance (VUSs) in family members may be pursued to help clarify VUS significance, but cannot be used to identify at-risk individuals at this time."  

For what it's worth, according to http://www.breastcancer.org/symptoms/diagnosis/other-gene-testing: "The ATM gene helps repair damaged DNA. DNA carries genetic information in cells. Inheriting two abnormal copies of this gene causes the disease ataxia-telangiectasia, a rare disease that affects brain development. Inheriting one abnormal ATM gene has been linked to an increased rate of breast cancer in some families because the abnormal gene stops the cells from repairing damaged DNA."

Now, if I am understanding everything correctly, there are variants or mutations of the ATM gene that the lab would classify as "pathogenic" or "likely pathogenic".  That means it can or there is strong evidence to suggest it does cause a disease, in this case, breast cancer.  These are the variants that are definitively linked to the increased rate of breast cancer.  However, my variation of the ATM gene is one they do not have enough information about or have conflicting information about.  Therefore, it's classified as a VUS (variant of uknown significance).  As they collect more data about this variant, it will likely be reclassified.  A small number of VUSs become reclassified as "pathogenic" or "likely pathogenic" and the majority of them are reclassified as "benign" or "likely benign".  

To that end, I am now part of a study being conducted by the genetic testing company.  This may provide an opportunity for other family members to be tested, if interested (if you're my family, I will send you more details*).  Additionally, they will notify my doctor when and how the variant is reclassified.  While it does not make much of a difference for me personally right now, it does feel pretty good to be able to contribute to the research.  I don't have to do much of anything and hopefully my vial of blood can help out those smart non-procrastinating scientists!

*Brothers, cousins, nieces and nephews:  The report has all kinds of numbers and terms I don't understand, but if you ever meet with a genetic counselor, it might be helpful to them!

[Last night I tried desperately to write a joke about VUSs and ROUSs (aka Rodents-Of-Unusual-Size a la The Princess Bride), but I failed miserably.  I felt like Mrs. Maisel bombing at The Gaslight Cafe.  So just keep in mind that every time I read or write VUSs, I think of ROUSs instead...]