GENETIC PROSTATE CANCER

€720

DNA Repair & Cancer Predisposition Genes

  1. ATM (Ataxia-Telangiectasia Mutated) – Involved in DNA damage repair; mutations increase the risk of breast, pancreatic, and prostate cancer, as well as ataxia-telangiectasia, a neurodegenerative disorder.

  2. BRCA1 (Breast Cancer 1) – A tumour suppressor gene crucial for DNA repair; mutations significantly increase the risk of breast, ovarian, prostate, and pancreatic cancer.

  3. BRCA2 (Breast Cancer 2) – Works similarly to BRCA1 in DNA repair; mutations raise the risk of breast, ovarian, prostate, and pancreatic cancer, as well as male breast cancer.

  4. CHEK2 (Checkpoint Kinase 2) – Regulates the DNA damage response; mutations increase the risk of breast, prostate, and colorectal cancer.

  5. EPCAM (Epithelial Cell Adhesion Molecule) – Affects cell adhesion and indirectly silences MSH2, leading to Lynch syndrome, which increases colorectal, endometrial, and other cancer risks.

Mismatch Repair & Prostate Cancer Genes

  1. HOXB13* (Homeobox B13) – Regulates prostate development; mutations are associated with hereditary prostate cancer.

  2. MLH1 (MutL Homolog 1) – A key DNA mismatch repair (MMR) gene; mutations cause Lynch syndrome, leading to increased risk of colorectal, endometrial, and other cancers.

  3. MSH2 (MutS Homolog 2) – Works with MLH1 in mismatch repair; mutations lead to Lynch syndrome, predisposing individuals to colorectal and endometrial cancer.

  4. MSH6 (MutS Homolog 6) – Works with MSH2 in mismatch repair; mutations cause Lynch syndrome, with a higher risk of endometrial and colorectal cancer.

  5. NBN (Nibrin, also known as NBS1) – Part of the DNA damage repair complex; mutations increase the risk of breast, prostate, and other cancers, and can cause Nijmegen breakage syndrome.

Other Cancer-Related Genes

  1. PALB2 (Partner and Localizer of BRCA2) – Works with BRCA2 in DNA repair; mutations significantly increase the risk of breast, ovarian, and pancreatic cancer.

  2. PMS2 (PMS1 Homolog 2, Mismatch Repair System Component) – Another MMR gene; mutations contribute to Lynch syndrome, though with a slightly lower cancer risk than MLH1 or MSH2 mutations.

  3. RAD51D (RAD51 Homolog D) – Involved in homologous recombination repair; mutations increase the risk of ovarian and breast cancer.

  4. TP53 (Tumour Protein p53) – Known as the "guardian of the genome", this tumour suppressor regulates cell growth and apoptosis; mutations cause Li-Fraumeni syndrome, leading to a very high risk of multiple early-onset cancers, including breast, brain, sarcomas, and leukaemias.

*The HOXB13 gene encodes a transcription factor involved in prostate gland development and cell differentiation.

HOXB13 G84E Variant (rs138213197)

  • This specific missense mutation (G84E) results in an amino acid change from glycine (G) to glutamic acid (E).

  • Clinical significance:

    • This variant is strongly associated with an increased risk of hereditary prostate cancer, particularly in Northern European populations.

    • Carriers of this mutation have a 2- to 5-fold increased risk of developing early-onset and familial prostate cancer.

    • It is not linked to aggressive prostate cancer, but rather to an increased lifetime risk of developing the disease.

Other Considerations

  • Testing for HOXB13 G84E is generally recommended for individuals with a strong family history of prostate cancer.

  • Unlike BRCA1/BRCA2 mutations, the impact on other cancers is limited, though some studies suggest a possible minor increase in breast cancer risk.