Cohort profile: a nationwide study in Dutch CHEK2 c.1100delC families using the infrastructure of the HEreditary Breast and Ovarian cancer study Netherlands – Hebon-CHEK2

• Published in: BMJ open Vol. 14; no. 10; p. e086688
• Main Authors: Schreurs, Maartje A.C., Adank, Muriel A, Hollestelle, Antoinette, de Groot, Rosa, Stommel-Jenner, Denise J, Van Asperen, Christi J., Ausems, Margreet G.E.M., Berger, Lieke P V, Blok, Marinus J, van Engelen, Klaartje, Hogervorst, Frans B L, Geurts-Giele, Willemina, Gille, Johan J P, Wevers, Marijke R, Schmidt, Marjanka K, Hooning, Maartje J.
• Format: Journal Article
• Language: English
• Published: England British Medical Journal Publishing Group 09-10-2024; BMJ Publishing Group LTD; BMJ Publishing Group
• Subjects: Adult; Aged; Breast cancer; Breast Neoplasms - genetics; Breast tumours; Cancer genetics; Cell cycle; Checkpoint Kinase 2 - genetics; Cohort Profile; Cohort Studies; Data collection; Diagnostic tests; Dutch language; Epidemiology; Family medical history; Female; Females; Genetic Predisposition to Disease; Heterozygote; Histopathology; Humans; Kinases; Medical diagnosis; Medical prognosis; Middle Aged; Netherlands - epidemiology; Ovarian cancer; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Patients; Pedigree; Questionnaires; Surveillance; Womens health; Netherlands; Breast tumours; Cancer genetics; Epidemiology
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2024-086688

PurposeCHEK2 c.1100delC is associated with an increased breast cancer risk in women. While this variant is prevalent in the Netherlands (1% in the general population), knowledge of aetiology and prognosis of breast cancer and other tumours in CHEK2 c.1100delC carriers is lacking. The nationwide HEreditary Breast and Ovarian cancer study the Netherlands (Hebon) cohort aims to answer study questions in families with an increased risk of breast cancer and ovarian cancer. While initially focusing on BRCA1/2-variant families, Hebon gradually expanded to include pathogenic variants in other genes associated with breast and/or ovarian cancer over time. This provides an excellent setting to establish a cohort to ultimately study the impact of CHEK2 c.1100delC on cancer risk prediction and surveillance, breast cancer treatment and prognosis.ParticipantsWe invited all heterozygous and homozygous CHEK2 c.1100delC indexes and tested female relatives. 1802 women were included, of whom 1374 were heterozygotes and 938 were breast cancer cases. Pedigrees were collected from all clinical genetic departments. Furthermore, participants completed a detailed questionnaire on hormonal and lifestyle factors, family history, cancer diagnosis and treatment.Findings to dateMean age at study inclusion was 53 years. Linkage with the Netherlands Cancer Registry showed a younger age at diagnosis in homozygotes (mean age 41.7 years) and heterozygotes (47.9 years) than non-carriers (51.2 years). Furthermore, carriers were more often diagnosed with grade 2, oestrogen receptor-positive breast cancer and more often developed contralateral breast cancer than non-carriers. Most women consumed alcohol regularly and about half never smoked.Future plansFurther data linkages with the Netherlands Cancer Registry will allow prospective follow-up and breast cancer risk assessment in unaffected women at the time of genetic testing, risk of contralateral breast cancer and survival in patients with breast cancer. Also, linkage with the nationwide network and registry of histopathology and cytopathology in The Netherlands (PALGA) allows us to retrieve tumour samples to study tumourigenesis.