Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer

Scientific paper - Original scientific paper

• Author: Kira Kirchner
• Author: Marija Gamulin
• Author: Tomislav Kuliš
• Author: Bianca Sievers
• Author: Željko Kaštelan
• Author: Davor Lessel
• Author's institution: University of Zagreb; School of Medicine; (Department of Clinical Oncology)
• Author's institution: University of Zagreb; School of Medicine; (Department of Urology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Urology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Oncology

Abstract (english)

Germline pathogenic and likely pathogenic (P/LP) variants in CHEK2 have been associated with increased prostate cancer (PrCa) risk. Our objective was to analyze their occurrence in Croatian PrCa men and to evaluate the clinical characteristics of P/LP variant carriers. Therefore, we analyzed CHEK2 in 150 PrCa patients unselected for age of onset, family history of PrCa or clinical outcome, and the frequency of identified variants was compared to findings in 442 cancer-free men, of Croatian ancestry. We identified four PrCa cases harboring a P/LP variant in CHEK2 (4/150, 2.67%), which reached a statistical significance (p = 0.004) as compared to the control group. Patients with P/LP variants in CHEK2 developed PrCa almost 9 years earlier than individuals with CHEK2 wild-type alleles (8.9 years; p = 0.0198) and had an increased risk for lymph node involvement (p = 0.0047). No association was found between CHEK2 status and further clinical characteristics, including the Gleason score, occurrence of aggressive PrCa, the tumor or metastasis stage. However, carriers of the most common P/LP CHEK2 variant, the c.1100delC, p.Thr367Metfs15*, had a significantly higher Gleason score (p = 0.034), risk for lymph node involvement (p = 0.0001), and risk for developing aggressive PrCa (p = 0.027). Thus, in a Croatian population, CHEK2 P/LP variant carriers were associated with increased risk for early onset prostate cancer, and carriers of the c.1100delC, p.Thr367Metfs15* had increased risk for aggressive PrCa.

• Keywords (english): Checkpoint Kinase 2 / genetics; Croatia; Germ-Line Mutation; Humans; Male; Neoplasm Grading; Prostate / pathology; Prostatic Neoplasms / genetics; Prostatic Neoplasms / pathology
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Genes
• Numbering: vol. 13, no. 11, 1955
• e-ISSN: 2073-4425
• DOI: https://doi.org/10.3390/genes13111955
• URN:NBN: urn:nbn:hr:105:609930
• Publication: 2022-10-27
• Document URL: https://www.mdpi.com/2073-4425/13/11/1955
• Type of resource: Text
• Access conditions: Open access
• Created on: 2023-07-13 07:40:00