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Genetic Susceptibility to Prostate Cancer

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Prostate Cancer

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Abstract

Prostate cancer (PCa) is the second most diagnosed cancer type globally and is one of the leading causes of death in men. Genetic susceptibility plays a significant role in PCa development with a reported heritability of 57%. Mutations in the different DNA damage repair (DDR) genes (BRCA1, BRCA2, CHEK2, ATM, and PALB2) and in DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) are hallmark of hereditary prostate cancer (HPCa) and are included in National Comprehensive Cancer Network (NCCN) guidelines for PCa germline genetic testing. In addition to rare high-risk mutations in susceptibility genes, polygenetic inheritance of low-risk germline variants in the form of single-nucleotide polymorphisms (SNPs) may be utilized to distinguish an individual’s susceptibility to PCa onset and progression. Over the past decade, the number of detected variants has increased to 269, due to the genome-wide association studies (GWAS). The large number of identified variants led to the development of polygenic risk scores (PRS) that aggregates common PCa-associated genetic variants into a single measure. The incorporation of diverse genetic analyses and PRS is highly anticipated to those individuals with positive PCa family history and may lead to improvements in clinical outcomes for this population through early prevention screening efforts.

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Authors and Affiliations

  1. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Tatjana Simic, Marija Matic & Djurdja Jerotic

  2. Institute of Medical and Clinical Biochemistry, Belgrade, Serbia

    Tatjana Simic, Marija Matic & Djurdja Jerotic

  3. Center of Excellence for Redox Medicine, Belgrade, Serbia

    Tatjana Simic, Marija Matic & Djurdja Jerotic

  4. Serbian Academy of Sciences and Arts, Belgrade, Serbia

    Tatjana Simic

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  1. Tatjana Simic
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  2. Marija Matic
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  1. Department of Biochemistry, Medical Faculty University of Nis, Nis, Serbia

    Gordana Kocic

  2. Serbian Academy of Science and Arts, Belgrade, Serbia

    Jovan Hadzi-Djokic

  3. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Tatjana Simic

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Simic, T., Matic, M., Jerotic, D. (2024). Genetic Susceptibility to Prostate Cancer. In: Kocic, G., Hadzi-Djokic, J., Simic, T. (eds) Prostate Cancer. Springer, Cham. https://doi.org/10.1007/978-3-031-51712-9_2

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