biostudies-literaturevan der Kooi ALFEuropean Union’s Seventh Framework ProgrammeEuropean Union’s Health ProgrammeNCIChildren Cancer Free FoundationDutch Cancer SocietyNCI NIH HHS1120-1133https://www.ebi.ac.uk/biostudies/studies/S-EPMC7970730biostudies-literatureUnknown36(4)<h4>Study question</h4>Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?<h4>Summary answer</h4>Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.<h4>What is known already</h4>Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability.<h4>Study design, size, duration</h4>CCS for the discovery cohort were identified fHuman reproduction (Oxford, England)Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.PMC7970730U01 CA1955476020302014–202076896720VU 2006-3622Yasui YChemaitilly WUitterlinden AGvan der Pal HJVersluys BModan-Moses DWinther JFKremer LCBrooke RJKaspers GLBresters DDirksen Uvan den Heuvel-Eibrink MMFossa SDvan Leeuwen FEde Vries ACHHaupt RLaven JSEKaiser MZolk OGrabow Dvan Dijk MKruseova JPluijm SMFvan den Berg MHRonckers CRHudson MMLoonen JJvan Dulmen-den Broeder ERobison LLLambalk CBTissing WJBeerendonk CCMBerger CKaatsch PKepak TSpix CKrijthe JHByrne JOverbeek ABroer Lvan der Heiden-van der Loo Mvan der Kooi ALFClemens EfalsePossible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function.<h4>Study question</h4>Do genetic variations in the DNA damage response pathway modify the adverse effect of alkylating agents on ovarian function in female childhood cancer survivors (CCS)?<h4>Summary answer</h4>Female CCS carrying a common BR serine/threonine kinase 1 (BRSK1) gene variant appear to be at 2.5-fold increased odds of reduced ovarian function after treatment with high doses of alkylating chemotherapy.<h4>What is known already</h4>Female CCS show large inter-individual variability in the impact of DNA-damaging alkylating chemotherapy, given as treatment of childhood cancer, on adult ovarian function. Genetic variants in DNA repair genes affecting ovarian function might explain this variability.<h4>Study design, size, duration</h4>CCS for the discovery cohort were identified f2021-01-01T00:00:00Z2021 Mar2026-05-03T09:27:40.617Z2024-11-20T17:48:41.498ZS-EPMC79707303358277810.1093/humrep/deaa342