Both parents have had BC

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ElaineD
ElaineD Member Posts: 2,265

Does anyone know of the risk to a daughter in this position? I must admit to never having heard of this happening, so was curious to see how much this increases what is already a very high risk if one parent has had BC.

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  • leaf
    leaf Member Posts: 8,188
    edited August 2013

    Well, unless the parent's families intermarried, its pretty unlikely that they both carry the same genetic mutation in the same gene.  Since the father has had bc, the daughter would automatically meet the  USFTF guidelines for having BRCA testing.

    There are other single genetic mutations that cause an increased incidence of breast cancer, but I will ignore those for now, since they are unusual.

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    The following assumes both parents are BRCA positive (which is an ASSUMPTION) and are heterozygotes.  (Heterozygotes in this case means they would have one 'wild type' or 'normal' gene and another gene with the BRCA mutation. It sounds like in this paper they have not detected any BRCA1 homozygotes {where they have 2 deleterious mutations in the BRCA1 genes http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653717/}  I assume there have not been any human BRCA2 homozygotes, but that is an assumption.):

    If you just go simple-minded, easy to understand scenario, and assume both parents are BRCA1 or 2 positive, and that the 2 genes are INDEPENDENT variables (which is an ASSUMPTION), and assuming the parents are heterozygotes, then the daughter has a 50% chance of inheriting a deleterious gene from the father, and a 50% chance of inheriting a deleterious gene  from the mother.  Thus, in this simple-minded, full of assumptions way, she might have a 75% chance of inheriting either 1 or 2 mutated genes from her parents. (0.5 x 0.5 = 0.25).  She'd have a 25% chance of not inheriting a BRCA mutation from either parent (using these assumptions, which are probably pretty reasonable.)

    Since there are multiple BRCA mutations, and each mutation can have different effects, we're probably on pretty uncertain ground.  For example, since BRCA genes seem to be involved in DNA repair, it is theoretically possible  (I'm not saying likely, but possible) that one mutation might, for example, make it harder for the DNA to fit into a certain repair enzyme, and another mutation might or might not change that effect.   In other words, the gene mutations may or may not be independent.  I'm not sure how that would affect the 75%statistics in the above case.

    In this paper, they describe 2 heterozygotes, and one of the people has had multiple cancers, and another is unaffected at age 65. http://www.ncbi.nlm.nih.gov/pubmed/17636421

    It would be important to find out the age of the mother's breast cancer.  But regardless, she would qualify for genetic testing from the USPTF guidelines.  (Is the affected daughter is in the UK? If so, I don't know what their BRCA testing guidelines are.) 

    These are the US PTF guidelines for BRCA testing:

    Although there currently are no standardized referral criteria, women with an increased-risk family history should be considered for genetic counseling to further evaluate their potential risks.

    Certain specific family history patterns are associated with an increased risk for deleterious mutations in the BRCA1 or BRCA2 gene. Both maternal and paternal family histories are important. For non-Ashkenazi Jewish women, these patterns include 2 first-degree relatives with breast cancer, 1 of whom received the diagnosis at age 50 years or younger; a combination of 3 or more first- or second-degree relatives with breast cancer regardless of age at diagnosis; a combination of both breast and ovarian cancer among first- and second-degree relatives; a first-degree relative with bilateral breast cancer; a combination of 2 or more first- or second-degree relatives with ovarian cancer regardless of age at diagnosis; a first- or second-degree relative with both breast and ovarian cancer at any age; and a history of breast cancer in a male relative.

    For women of Ashkenazi Jewish heritage, an increased-risk family history includes any first-degree relative (or 2 second-degree relatives on the same side of the family) with breast or ovarian cancer.http://www.uspreventiveservicestaskforce.org/uspstf05/brcagen/brcagenrs.htm#clinical

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    However, its certainly possible that NEITHER of her parents have a single deleterious mutation.

    Since most breast cancers in women (about 90%) are NOT linked to single deleterious mutations, it is certainly possible she could have no increased risk at all.   http://www.cancer.gov/cancertopics/factsheet/Risk/BRCA  I'm sure that not ALL men who get breast cancer have a BRCA1 or BRCA2 deleterious mutation.  In this small study, 5/19 men with breast cancer had a BRCA mutation.http://breast-cancer-research.com/content/4/1/R2

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    So, to summarize,  if she was in the US, she'd qualify  by the USPTF guidelines for BRCA testing just because her father had bc, but, using simpleminded statistics that use lots of assumptions, she'd have AT LEAST a 25% chance of NOT being having one or more BRCA deleterious mutation(s).

  • ElaineD
    ElaineD Member Posts: 2,265
    edited October 2010

    Fantastic Leaf-I thought you would have the answer! She is indeed in the UK, and has seen a geneticist-who has admitted they didn't have an answer.

    Would it be ok if I copied over your answer to her, as the links are a good starting point for her?

  • leaf
    leaf Member Posts: 8,188
    edited October 2010

    Sure! (The 75% figure is calculated by 0.5 x 0.5 = 0.25 chance.) 

  • ElaineD
    ElaineD Member Posts: 2,265
    edited October 2010

    Thanks-as you can imagine, she's prety stressed at their claim "they don't know"!

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