Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors
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Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors. / Kirchner, Kira; Seidel, Christoph; Paulsen, Finn-Ole; Sievers, Bianca; Bokemeyer, Carsten; Lessel, Davor.
in: J CLIN MED, Jahrgang 12, Nr. 22, 7065, 13.11.2023.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Further Association of Germline CHEK2 Loss-of-Function Variants with Testicular Germ Cell Tumors
AU - Kirchner, Kira
AU - Seidel, Christoph
AU - Paulsen, Finn-Ole
AU - Sievers, Bianca
AU - Bokemeyer, Carsten
AU - Lessel, Davor
PY - 2023/11/13
Y1 - 2023/11/13
N2 - Testicular germ cell tumors (TGCTs) represent the most frequent malignancy in young adult men and have one the highest heritability rates among all cancers. A recent multicenter case-control study identified CHEK2 as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed CHEK2 in 129 TGCT cases unselected for age of onset, histology, clinical outcome, and family history of any cancer, and the frequency of identified variants was compared to findings in 27,173 ancestry-matched cancer-free men. We identified four TGCT cases harboring a P/LP variant in CHEK2 (4/129, 3.10%), which reached statistical significance (p = 0.0191; odds ratio (OR), 4.06; 95% CI, 1.59-10.54) as compared to the control group. Cases with P/LP variants in CHEK2 developed TGCT almost 6 years earlier than individuals with CHEK2 wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between CHEK2 status and further clinical and histopathological characteristics, including histological subtypes, the occurrence of aggressive TGCT, family history of TGCT, and family history of any cancer. In addition, we found significant enrichment for the low-penetrance CHEK2 variant p.Ile157Thr (p = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45-9.55). Thus, we provide further independent evidence of CHEK2 being a moderate-penetrance TGCT predisposition gene.
AB - Testicular germ cell tumors (TGCTs) represent the most frequent malignancy in young adult men and have one the highest heritability rates among all cancers. A recent multicenter case-control study identified CHEK2 as the first moderate-penetrance TGCT predisposition gene. Here, we analyzed CHEK2 in 129 TGCT cases unselected for age of onset, histology, clinical outcome, and family history of any cancer, and the frequency of identified variants was compared to findings in 27,173 ancestry-matched cancer-free men. We identified four TGCT cases harboring a P/LP variant in CHEK2 (4/129, 3.10%), which reached statistical significance (p = 0.0191; odds ratio (OR), 4.06; 95% CI, 1.59-10.54) as compared to the control group. Cases with P/LP variants in CHEK2 developed TGCT almost 6 years earlier than individuals with CHEK2 wild-type alleles (5.67 years; 29.5 vs. 35.17). No association was found between CHEK2 status and further clinical and histopathological characteristics, including histological subtypes, the occurrence of aggressive TGCT, family history of TGCT, and family history of any cancer. In addition, we found significant enrichment for the low-penetrance CHEK2 variant p.Ile157Thr (p = 0.0259; odds ratio (OR), 3.69; 95% CI, 1.45-9.55). Thus, we provide further independent evidence of CHEK2 being a moderate-penetrance TGCT predisposition gene.
U2 - 10.3390/jcm12227065
DO - 10.3390/jcm12227065
M3 - SCORING: Journal article
C2 - 38002677
VL - 12
JO - J CLIN MED
JF - J CLIN MED
SN - 2077-0383
IS - 22
M1 - 7065
ER -
