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

TY - JOUR

T1 - Comprehensive Clinical and Genetic Analysis of CHEK2 in Croatian Men with Prostate Cancer

AU - Kirchner, Kira

AU - Gamulin, Marija

AU - Kulis, Tomislav

AU - Sievers, Bianca

AU - Kastelan, Zeljko

AU - Lessel, Davor

PY - 2022/10/27

Y1 - 2022/10/27

N2 - 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.

AB - 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.

KW - Male

KW - Humans

KW - Germ-Line Mutation

KW - Croatia

KW - Prostatic Neoplasms/genetics

KW - Prostate/pathology

KW - Neoplasm Grading

KW - Checkpoint Kinase 2/genetics

U2 - 10.3390/genes13111955

DO - 10.3390/genes13111955

M3 - SCORING: Journal article

C2 - 36360192

VL - 13

JO - GENES-BASEL

JF - GENES-BASEL

SN - 2073-4425

IS - 11

M1 - 1955

ER -