Home General discussion



Has anyone tested positive for the RAD gene mutation?

TasiaTasia Sydney, NSWMember Posts: 117
Thank you x

Comments

  • AbbydogAbbydog Adelaide, South AustraliaMember Posts: 234
    I've been trying to look this up and haven't found much. Were you given any printed information?
    Is it definitely different to BRCA 1 and BRCA 2?

  • AfraserAfraser MelbourneMember Posts: 3,424
    From a research paper online - sorry, can’t vouch for its accuracy. 

    Abstract

    Deleterious mutations in the RAD51C gene, which encodes a DNA double-strand break (DSB) repair protein, have been reported to confer high-penetrance susceptibility to both breast and ovarian cancer. To confirm this we conducted a mutation screen of the RAD51C gene in 192 probands from high-risk breast and/or ovarian cancer families that do not carry BRCA1 or BRCA2 mutations. The nine exons of the RAD51C gene containing protein coding sequence were screened for mutations in genomic DNA from family probands by high-resolution melting (HRM) analysis and direct DNA sequencing. Four missense variants, p.Ser364Gly, p.Ala126Thr, p.Val169Ala, and p.Thr287Ala were detected in six patients. The p.Ser364Gly variant is a novel variant predicted to have little influence on RAD51C activity. The p.Ala126Thr and p.Val169Ala variants have been reported to have no association with risk of breast cancer in a case-control study. However, p.Thr287Ala disrupts the DNA repair activity of RAD51C, suggesting some influence on risk. Consistent with published results from similar follow-up studies, we suggest that RAD51C mutations are rare events among high-risk breast cancer and breast/ovarian cancer families. Large population-based studies will be needed to reliably assess the prevalence and penetrance of inactivating mutations in the RAD51C susceptibility gene.

  • TasiaTasia Sydney, NSWMember Posts: 117
    @Abbydog and @Afraser - thank you to you both for looking this up xx. I also tried to find some decent information but as you both discovered, there is minimal information available. 

    No, I havenʻt been given any printed info. Both specialists including the Prof. Radio Onco had very little knowledge themselves. The lab Chief Scientist is who they obtained little info they could share with me. Then the conversation moved to ʻmust have - DMX and hysterectomy, etc, tell my family members, relatives...ʻ 

    Now I am faced with ʻwhat do I do?ʻ, if anything with reconstructive surgery. If I am no longer going to have radiotherapy, they will perform immediate reconstruction, if I consent to that. If I must have radiotherapy, I cannot have immediate reconstruction. Will heal and then have the hysterectomy, ovaries, etc, and reconstruction. What order, Iʻm not sure :(
  • AfraserAfraser MelbourneMember Posts: 3,424
    That’s the unfortunate side of learning more and more about breast cancer - some of the newer discoveries are still very unclear. Which makes decisions so much harder. I can’t advise at all on reconstruction, sorry - I remain mono-boobed, happy with it but it’s not everyone’s choice. So step by step, decision on radiotherapy and then on from there. Best wishes. 
  • TasiaTasia Sydney, NSWMember Posts: 117
    I spoke to onc; I have RAD51C which is now known to be associated with TNBC. There is also a RAD51D - thatʻs not me. 

  • AbbydogAbbydog Adelaide, South AustraliaMember Posts: 234
    Could the Onc give you some information? Or refer you to a reliable website.
    It would be better than you being misinformed. Not saying that you are.

  • Jen2019Jen2019 South West Sydney Member Posts: 25
    Tasia 

    I found a paper published online dated Sept 28,2011. It says it is peer reviewed but not sure.

    RAD51C Germline Mutations in Breast and Ovarian Cancer Cases from High-Risk Families

    https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0025632

    Abstract

    BRCA1 and BRCA2 are the most well-known breast cancer susceptibility genes. Additional genes involved in DNA repair have been identified as predisposing to breast cancer. One such gene, RAD51C, is essential for homologous recombination repair. Several likely pathogenic RAD51C mutations have been identified in BRCA1- and BRCA2-negative breast and ovarian cancer families. We performed complete sequencing of RAD51C in germline DNA of 286 female breast and/or ovarian cancer cases with a family history of breast and ovarian cancers, who had previously tested negative for mutations in BRCA1 and BRCA2. We screened 133 breast cancer cases, 119 ovarian cancer cases, and 34 with both breast and ovarian cancers. Fifteen DNA sequence variants were identified; including four intronic, one 5′ UTR, one promoter, three synonymous, and six non-synonymous variants. None were truncating. The in-silico SIFT and Polyphen programs were used to predict possible pathogenicity of the six non-synonomous variants based on sequence conservation. G153D and T287A were predicted to be likely pathogenic. Two additional variants, A126T and R214C alter amino acids in important domains of the protein such that they could be pathogenic. Two-hybrid screening and immunoblot analyses were performed to assess the functionality of these four non-synonomous variants in yeast. The RAD51C-G153D protein displayed no detectable interaction with either XRCC3 or RAD51B, and RAD51C-R214C displayed significantly decreased interaction with both XRCC3 and RAD51B (p<0.001). Immunoblots of RAD51C-Gal4 activation domain fusion peptides showed protein levels of RAD51C-G153D and RAD51C-R214C that were 50% and 60% of the wild-type, respectively. Based on these data, the RAD51C-G153D variant is likely to be pathogenic, while the RAD51C- R214C variant is hypomorphic of uncertain pathogenicity. These results provide further support that RAD51C is a rare breast and ovarian cancer susceptibility gene.


  • Jen2019Jen2019 South West Sydney Member Posts: 25
    edited January 27
    Tasia


    Another biomedical paper published on 2019 link below for your perusal. Not sure again if this is legit.

    https://pubmed.ncbi.nlm.nih.gov/31409076/


    Recommendations for Preventive Care for Women with Rare Genetic Cause of Breast and Ovarian Cancer

    Abstract

    An inherited predisposition to breast cancer underlies 5-10% of breast tumors. High-risk BRCA1 and BRCA2 genes result in an 85% lifetime risk of breast cancer and a 20-60% lifetime risk of ovarian cancer. Next-generation sequencing or massive parallel sequencing are now established testing methods that enable screening for many genes that predispose to heterogeneous hereditary cancer syndromes (22 genes are required by the health insurance companies). In addition to BRCA1 and BRCA2, inherited mutations in other genes predispose to breast and/or ovarian cancer. High-risk breast cancer genes include TP53, STK11, CDH1, PTEN, PALB2, and NF1, while moderate-risk (2-4 times increased risk) breast cancer genes include ATM, CHEK2, and NBN. Moderate risk is also suggested for Lynch syndrome, MUTYH, BRIP1, RAD51C, RAD51D, BARD1, FANCA, FANCC, FANCM, BLM, WRN genes. In heterozygotes for other recessive syndromes the risk of developing breast cancer is subject to current research. Low-risk genes are (mostly) irrelevant from a clinical perspective. Other genes that increase the risk of ovarian cancer include the genes for Lynch syndrome, the BRIP1, RAD51C and RAD51D genes. Preventive care should be proposed based on assumed cumulative breast cancer risk (see http: //www.mamo.cz): a risk of &gt;20% for BRCA1/2, TP53, PTEN, STK11, CDH1, PALB2, CHEK2, ATM, and NF1; and a risk of 10-20% for BRIP1, RAD51C, RAD51B, BARD1, FANCA, FANCC, FANCM, NBN, BLM, and WRN. The genetic risk should be assessed by a geneticist and be based on inherited mutations and empirical risk according to family history. Prophylactic mastectomy is considered for high-risk gene carriers but not for moderate-risk gene carriers; however, it may be considered if there is an underlying family history, a risk of parenchyma of the mammary gland, or other risk factors. Ovarian cancer risk increases significantly in carriers of the BRIP1, RAD51C, and RAD51D genes. For prevention of ovarian cancer, prophylactic salpingo-oophorectomy is an important component of preventive care. In ovarian cancer families with no identified risk germline mutation, preventive salpingo-oophorectomy is not routinely recommended but may be considered as the only efficient method of prevention due to the increased empirical risk (4 times) of ovarian cancer in first-degree relatives. Supported by the grant project MH CZ - RVO (MMCI, 00209805), AZV 15-27695A and AZV 16-29959A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Submitted: 17. 5. 2019 Accepted: 31. 5. 2019.


  • TasiaTasia Sydney, NSWMember Posts: 117
    Abbydog said:
    Could the Onc give you some information? Or refer you to a reliable website.
    It would be better than you being misinformed. Not saying that you are.

    The only limited info was heavily saturated by medical jargon so I received a verbal summary. No specific website - info is basically similar to what Jen has posted (thank you Jen). Lean on substance. What I do know from my own research and Onc discussions is that RAD51C has a strong association with TNBC and very high risk of ovarian cancer. Hence, preventative surgery needed to reduce cancers interest in taking up residence elsewhere; as we know, no guarantees.
  • FLCloverFLClover Sydney Member Posts: 953
    All fingers crossed 🤞🤞🤞🤞🤞 @Tasia that the preventative surgeries work 🍀🍀🍀
  • AbbydogAbbydog Adelaide, South AustraliaMember Posts: 234
    Dear Tasia,
    I'm so sorry that there isn't any available easy to read information.
    Do you have a date for surgery?
    You had said early in the week.
    Good luck, and best wishes.
Sign In or Register to comment.