| Summary: | Germline pathogenic and likely pathogenic (P/LP) variants in <i>CHEK2</i> 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 <i>CHEK2</i> 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 <i>CHEK2</i> (4/150, 2.67%), which reached a statistical significance (<i>p</i> = 0.004) as compared to the control group. Patients with P/LP variants in <i>CHEK2</i> developed PrCa almost 9 years earlier than individuals with <i>CHEK2</i> wild-type alleles (8.9 years; <i>p</i> = 0.0198) and had an increased risk for lymph node involvement (<i>p</i> = 0.0047). No association was found between <i>CHEK2</i> 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.Thr367Met<i>fs</i>15*, had a significantly higher Gleason score (<i>p</i> = 0.034), risk for lymph node involvement (<i>p</i> = 0.0001), and risk for developing aggressive PrCa (<i>p</i> = 0.027). Thus, in a Croatian population, <i>CHEK2</i> P/LP variant carriers were associated with increased risk for early onset prostate cancer, and carriers of the c.1100delC, p.Thr367Met<i>fs</i>15* had increased risk for aggressive PrCa.
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