Tea Nizic-Kos1, Mateja Krajc2, Ana Blatnik2, Vida Stegel3, Petra Skerl3, Srdjan Novakovic3, Barbara Gazic4, Nikola Besic5. 1. Department of Surgical Oncology, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia. 2. Cancer Genetics Clinic, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia. 3. Department of Molecular Diagnostics, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia. 4. Department of Pathology, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia. 5. Department of Surgical Oncology, Institute of Oncology, Zaloska 2, 1000, Ljubljana, Slovenia. nbesic@onko-i.si.
Abstract
BACKGROUND: Currently, data on pathogenic variants in the CHEK2 gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families with CHEK2 pathogenic variants in Slovenia. METHODS: In the years 2014 to 2019, CHEK2 pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution. Altogether, the study enrolled 75 individuals from 50 CHEK2 families who were carriers of a CHEK2 PV/LPV. The clinical data on 41 BC patients with CHEK2 PV/LPV and other carriers of CHEK2 PV/LPV from Slovenia were collected and analyzed. RESULTS: Breast cancer was diagnosed in 41 of 75 CHEK2 PV/LPV carriers (40 females, 1 male). The mean age at BC diagnosis was 42.8 years (range, 21-63 years), and 27 (65.8%) of the 41 of patients with BC had a positive family history for BC. Contralateral BC (CBC) was observed in 8 (19.5%) of the 41 patients (mean age, 55.6 years). Of 12 patients with human epidermal growth factor receptor 2 (HER2)-positive tumor type, a c.444+1G > A PV/LPV was detected in 4 patients, c.349A > G in 3 patients, deletion of exons 9-10 in 3 patients, deletion of exon 8 in 1 patient, and c.1427C > T PV/LPV in 1 patient. CONCLUSION: Bilateral BC was diagnosed in as many as 19.5% of the Slovenian BC patients with CHEK2 PV/LPVs. Breast cancer associated with a germline CHEK2 PV/LPV occurs in younger patients compared with sporadic BC.
BACKGROUND: Currently, data on pathogenic variants in the CHEK2 gene and their impact on cancer risk are lacking. This study aimed to explore the characteristics of breast cancer (BC) patients from families with CHEK2 pathogenic variants in Slovenia. METHODS: In the years 2014 to 2019, CHEK2 pathogenic variants/likely pathogenic variants (PV/LPVs) were found in probands from 50 different families who underwent genetic counseling and testing using a multigene panel at the authors' institution. Altogether, the study enrolled 75 individuals from 50 CHEK2 families who were carriers of a CHEK2 PV/LPV. The clinical data on 41 BC patients with CHEK2 PV/LPV and other carriers of CHEK2 PV/LPV from Slovenia were collected and analyzed. RESULTS: Breast cancer was diagnosed in 41 of 75 CHEK2 PV/LPV carriers (40 females, 1 male). The mean age at BC diagnosis was 42.8 years (range, 21-63 years), and 27 (65.8%) of the 41 of patients with BC had a positive family history for BC. Contralateral BC (CBC) was observed in 8 (19.5%) of the 41 patients (mean age, 55.6 years). Of 12 patients with human epidermal growth factor receptor 2 (HER2)-positive tumor type, a c.444+1G > A PV/LPV was detected in 4 patients, c.349A > G in 3 patients, deletion of exons 9-10 in 3 patients, deletion of exon 8 in 1 patient, and c.1427C > T PV/LPV in 1 patient. CONCLUSION: Bilateral BC was diagnosed in as many as 19.5% of the Slovenian BC patients with CHEK2 PV/LPVs. Breast cancer associated with a germline CHEK2 PV/LPV occurs in younger patients compared with sporadic BC.
Authors: Petra Kleiblova; Lenka Stolarova; Katerina Krizova; Filip Lhota; Jan Hojny; Petra Zemankova; Ondrej Havranek; Michal Vocka; Marta Cerna; Klara Lhotova; Marianna Borecka; Marketa Janatova; Jana Soukupova; Jan Sevcik; Martina Zimovjanova; Jaroslav Kotlas; Ales Panczak; Kamila Vesela; Jana Cervenkova; Michaela Schneiderova; Monika Burocziova; Kamila Burdova; Viktor Stranecky; Lenka Foretova; Eva Machackova; Spiros Tavandzis; Stanislav Kmoch; Libor Macurek; Zdenek Kleibl Journal: Int J Cancer Date: 2019-05-20 Impact factor: 7.396