A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer

Lynne Kerr, Matthew J. Rewhorn, Mark Longmuir, Sioban Fraser, Shaun Walsh, Nicola Andrew, Hing Y. Leung (Lead / Corresponding author)

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    Abstract

    Background: Prostate cancer (PC) is a major health concern for men worldwide, with an estimated lifetime risk of ~14 %. A recent comprehensive analysis of mutational processes revealed ageing and mismatch repair as the only altered processes in PC. We wish to test if a cohort of men with inherited risk of mismatch repair defect through BRCA1/2 or Lynch Syndrome mutations represents a target population for prostate cancer testing. 

    Methods: Fifty-eight men (aged 40-69 years) from families with a history of BRCA1/2 or HNPCC/Lynch mutations were invited to take part. Men with PSA >3.0 ng/ml were recommended to have transrectal ultrasound-guided prostatic biopsies. 

    Results: Overall 1 of 7 (14 %) and 1 of 20 (5 %) men with BRCA1/2 mutations were positive for a diagnosis of prostate cancer. In men with Lynch syndrome, 1 of 4 (25 %) was diagnosed to have prostate cancer. The index case with Lynch syndrome harbours a heterozygous mutation in the mismatch repair MSH6 gene. Near to complete loss of MSH6 immunoreactivity in the prostate tumour supports silencing of the remaining MSH6 allele during prostate carcinogenesis. Conclusion: The finding of near-to-complete loss of MSH6 expression in affected men with a family history of Lynch Syndrome supports its mechanistic involvement during prostate carcinogenesis. This work therefore contributes to the argument that, in certain male populations, Lynch Syndrome mutations are biologically implicated in men with prostate cancer.

    Original languageEnglish
    Article number529
    Pages (from-to)1-6
    Number of pages6
    JournalBMC Cancer
    Volume16
    DOIs
    Publication statusPublished - 25 Jul 2016

    Fingerprint

    Hereditary Nonpolyposis Colorectal Neoplasms
    Prostatic Neoplasms
    Cohort Studies
    Mutation
    DNA Mismatch Repair
    Prostate
    Carcinogenesis
    Men's Health
    Health Services Needs and Demand
    Alleles
    Biopsy
    Population
    Genes
    Neoplasms

    Keywords

    • BRCA1/2
    • Lynch Syndrome
    • Mismatch repair
    • MSH6 Mutation
    • Prostate cancer

    Cite this

    Kerr, L., Rewhorn, M. J., Longmuir, M., Fraser, S., Walsh, S., Andrew, N., & Leung, H. Y. (2016). A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer. BMC Cancer, 16, 1-6. [529]. https://doi.org/10.1186/s12885-016-2573-x
    Kerr, Lynne ; Rewhorn, Matthew J. ; Longmuir, Mark ; Fraser, Sioban ; Walsh, Shaun ; Andrew, Nicola ; Leung, Hing Y. / A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer. In: BMC Cancer. 2016 ; Vol. 16. pp. 1-6.
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    abstract = "Background: Prostate cancer (PC) is a major health concern for men worldwide, with an estimated lifetime risk of ~14 {\%}. A recent comprehensive analysis of mutational processes revealed ageing and mismatch repair as the only altered processes in PC. We wish to test if a cohort of men with inherited risk of mismatch repair defect through BRCA1/2 or Lynch Syndrome mutations represents a target population for prostate cancer testing. Methods: Fifty-eight men (aged 40-69 years) from families with a history of BRCA1/2 or HNPCC/Lynch mutations were invited to take part. Men with PSA >3.0 ng/ml were recommended to have transrectal ultrasound-guided prostatic biopsies. Results: Overall 1 of 7 (14 {\%}) and 1 of 20 (5 {\%}) men with BRCA1/2 mutations were positive for a diagnosis of prostate cancer. In men with Lynch syndrome, 1 of 4 (25 {\%}) was diagnosed to have prostate cancer. The index case with Lynch syndrome harbours a heterozygous mutation in the mismatch repair MSH6 gene. Near to complete loss of MSH6 immunoreactivity in the prostate tumour supports silencing of the remaining MSH6 allele during prostate carcinogenesis. Conclusion: The finding of near-to-complete loss of MSH6 expression in affected men with a family history of Lynch Syndrome supports its mechanistic involvement during prostate carcinogenesis. This work therefore contributes to the argument that, in certain male populations, Lynch Syndrome mutations are biologically implicated in men with prostate cancer.",
    keywords = "BRCA1/2, Lynch Syndrome, Mismatch repair, MSH6 Mutation, Prostate cancer",
    author = "Lynne Kerr and Rewhorn, {Matthew J.} and Mark Longmuir and Sioban Fraser and Shaun Walsh and Nicola Andrew and Leung, {Hing Y.}",
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    Kerr, L, Rewhorn, MJ, Longmuir, M, Fraser, S, Walsh, S, Andrew, N & Leung, HY 2016, 'A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer', BMC Cancer, vol. 16, 529, pp. 1-6. https://doi.org/10.1186/s12885-016-2573-x

    A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer. / Kerr, Lynne; Rewhorn, Matthew J.; Longmuir, Mark; Fraser, Sioban; Walsh, Shaun; Andrew, Nicola; Leung, Hing Y. (Lead / Corresponding author).

    In: BMC Cancer, Vol. 16, 529, 25.07.2016, p. 1-6.

    Research output: Contribution to journalArticle

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    T1 - A cohort analysis of men with a family history of BRCA1/2 and Lynch mutations for prostate cancer

    AU - Kerr, Lynne

    AU - Rewhorn, Matthew J.

    AU - Longmuir, Mark

    AU - Fraser, Sioban

    AU - Walsh, Shaun

    AU - Andrew, Nicola

    AU - Leung, Hing Y.

    PY - 2016/7/25

    Y1 - 2016/7/25

    N2 - Background: Prostate cancer (PC) is a major health concern for men worldwide, with an estimated lifetime risk of ~14 %. A recent comprehensive analysis of mutational processes revealed ageing and mismatch repair as the only altered processes in PC. We wish to test if a cohort of men with inherited risk of mismatch repair defect through BRCA1/2 or Lynch Syndrome mutations represents a target population for prostate cancer testing. Methods: Fifty-eight men (aged 40-69 years) from families with a history of BRCA1/2 or HNPCC/Lynch mutations were invited to take part. Men with PSA >3.0 ng/ml were recommended to have transrectal ultrasound-guided prostatic biopsies. Results: Overall 1 of 7 (14 %) and 1 of 20 (5 %) men with BRCA1/2 mutations were positive for a diagnosis of prostate cancer. In men with Lynch syndrome, 1 of 4 (25 %) was diagnosed to have prostate cancer. The index case with Lynch syndrome harbours a heterozygous mutation in the mismatch repair MSH6 gene. Near to complete loss of MSH6 immunoreactivity in the prostate tumour supports silencing of the remaining MSH6 allele during prostate carcinogenesis. Conclusion: The finding of near-to-complete loss of MSH6 expression in affected men with a family history of Lynch Syndrome supports its mechanistic involvement during prostate carcinogenesis. This work therefore contributes to the argument that, in certain male populations, Lynch Syndrome mutations are biologically implicated in men with prostate cancer.

    AB - Background: Prostate cancer (PC) is a major health concern for men worldwide, with an estimated lifetime risk of ~14 %. A recent comprehensive analysis of mutational processes revealed ageing and mismatch repair as the only altered processes in PC. We wish to test if a cohort of men with inherited risk of mismatch repair defect through BRCA1/2 or Lynch Syndrome mutations represents a target population for prostate cancer testing. Methods: Fifty-eight men (aged 40-69 years) from families with a history of BRCA1/2 or HNPCC/Lynch mutations were invited to take part. Men with PSA >3.0 ng/ml were recommended to have transrectal ultrasound-guided prostatic biopsies. Results: Overall 1 of 7 (14 %) and 1 of 20 (5 %) men with BRCA1/2 mutations were positive for a diagnosis of prostate cancer. In men with Lynch syndrome, 1 of 4 (25 %) was diagnosed to have prostate cancer. The index case with Lynch syndrome harbours a heterozygous mutation in the mismatch repair MSH6 gene. Near to complete loss of MSH6 immunoreactivity in the prostate tumour supports silencing of the remaining MSH6 allele during prostate carcinogenesis. Conclusion: The finding of near-to-complete loss of MSH6 expression in affected men with a family history of Lynch Syndrome supports its mechanistic involvement during prostate carcinogenesis. This work therefore contributes to the argument that, in certain male populations, Lynch Syndrome mutations are biologically implicated in men with prostate cancer.

    KW - BRCA1/2

    KW - Lynch Syndrome

    KW - Mismatch repair

    KW - MSH6 Mutation

    KW - Prostate cancer

    U2 - 10.1186/s12885-016-2573-x

    DO - 10.1186/s12885-016-2573-x

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