Brca 1 & 2

Gene Health
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New here - my doctor tested me for BRCA 1 & 2 and other hereditary cancer genes and all came back negative, but my results from 23andme in Livewello show that I do have BRCA 1 & 2. My question is, do doctors only check for a few certain variations of the gene or do the tests for the hundreds that are know? Do they only test for the ones that are know to be negative?

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I was tested after ovarian cancer treatment and tested negative. However, my 23&Me data, I have many SNPs in Livewello show all kinds of cancers and it includes breast. I am assuming it’s because if homogeneous and heterogeneous. I wish to know the same.

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I have no personal knowledge or experience re. breast cancer, but a couple tidbits for your consideration: Forgive me if you already know all the following ; I don’t want to assume anything.

  1. Livewello only shows your phenotype for various SNPs (identified “parts” of genes); i.e. whether you have the “wild” (more common) form, or the “variant” (less common) form of genotype. As we inherit two copies of DNA- one from each parent, genotyping shows you both copies (one from each of the intertwined strands) of your DNA coding for that SNP.
    Livewello only reports whether you have the “variant” form (on either or both strands) or the “wild” type, and per standard, expresses the phenotype as: -/- (both negative for the variant); -/+ if one of the two copies is “positive” for the variant, and +/+ if both copies are the variant. In the latter case, you’re said to be “homogeneous” for the variant.; or in the mixed case, “heterogeneous”.

  2. It’s crucial to understand, when looking at your SNPs, that the “minor”, or “variant” form is not always the one that is associated with risk of any particular disease. In fact, sometimes it’s the variant that offers a reduction of risk (some protection) from a disease. I’ve learned that the hard way…interpreting red “homozygous” SNPs as a disease risk, only to later learn that in some of those cases I actually had a lower risk of disease.
    That’s where a more thorough review of research on gene-disease associations is helpful and necessary. Livewello does include links or summaries of studies re. various associations between SNPs and disease conditions - so it’s worth reading those.
    This also means we must avoid jumping to conclusions about our Livewello reports, especially re. interpretation of ‘homozygosity’ or heterozygosity.

  3. I also uploaded DNA to Promethease.com. After doing so, you can download a web-browsable extract of the processed part of your genome; which you can then run at any time on your own pc . It allows filtering for such things as disease conditions , specific genes, and more. When I filter for genes BRCA1 & 2, it shows my genotype for a total of 25 SNPs; and for each one it may have a report or partial report on associations, risk, etc.

I use Promethease and LIvewello side by side. That’s in part because the former doesn’t allow you to filter for a single SNP; and occasionally your review of gene-disease associations may point to a specific SNP.

Note that the two programs may use different genomic “builds” , however; so one may identify the encoding of a gene SNP from the “forward” (or plus) strand while the other may use the “reverse” or minus strand. This can be confusing. (I posted on this before, at: SNPs with GG but Outcome should be CC .)

  1. The DNA processing sites (like Ancestry, 23andMe, etc.) only process a portion of your genome, and I suspect that Livewello and such programs only then report on a subset of what your raw dna file contains. So while they do provide a lot of useful information, it is not “complete”.

It’s also important to keep in mind that being "homozygous for some disease-associated SNP is not the end of story. There are so many gene-gene interactions; and the science is only in its infancy in understanding them… Some SNPs may protect you at the same time others may increase your risk.
Also, of course, DNA isn’t exactly destiny. One may be at increased risk because of heredity but it is possible to lower (and likewise, increase) the risk via lifestyle / environmental factors.

I found this page to be informative: https://www.snpedia.com/index.php/Breast_cancer …worth reading. Among other things, it includes a list of genes and SNPs id’d as risk factors. No doubt there are many other lists of such risk-alleles elsewhere.

I recommend you consult with your MD or other professional to ask for the list of Gene SNPs that were tested, and possibly compare that to other research. I don’t know, but would guess that medical gene testing may look at those SNPs most strongly associated in the research with breast cancer.

If in your reading and looking at Livewello (and Promethease, if you use it) you find some reported SNPs that may be of concern to you, you can certainly bring those to the attention of your doctor. Just remember not to jump to conclusions!

While some MDs may discourage or dismiss such patient-conducted investigation, others will be receptive, because as I said, the body of knowledge in genetics is still at a pretty early stage and with research, is growing all the time. My own MDs, for example, have been for the most part quite receptive of any information I can provide on my own conditions and genomics.

Good luck.

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Thank you so much for providing very detailed and great feedback!

Much gratitude!

ncdesertprincess

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