Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function
| العنوان: | Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function |
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| المؤلفون: | van Leeuwen Fe, van Dijk M, Dalit Modan-Moses, Dorine Bresters, Claudia Spix, C.B. Lambalk, Jacqueline J. Loonen, Eva Clemens, A. Overbeek, Wassim Chemaitilly, van den Berg Mh, Gertjan L. Kaspers, Beerendonk Ccm, L. L. Robison, Sophie D. Fosså, van der Heiden-van der Loo M, Desiree Grabow, Peter Kaatsch, A.G. Uitterlinden, Melissa M. Hudson, van den Heuvel-Eibrink M, Russell J. Brooke, L. C. M. Kremer, van der Pal Hj, W.J.E. (Wim) Tissing, Falck Winther J, van der Kooi Alf, J. Kruseova, Uta Dirksen, Laven Jse, Claire Berger, Tomáš Kepák, Ronckers Cr, James M. Byrne, Pluijm Smf, Melanie Kaiser, de Vries Ach, Mvan Dulmen-den Broeder E, Linda Broer, Yutaka Yasui, Jesse H. Krijthe, Birgitta Versluys, O. Zolk, Riccardo Haupt |
| المساهمون: | Guided Treatment in Optimal Selected Cancer Patients (GUTS), Pediatrics, Obstetrics and gynaecology, Amsterdam Reproduction & Development (AR&D), CCA - Cancer Treatment and quality of life, CCA - Cancer biology and immunology, Obstetrics & Gynecology, Internal Medicine |
| المصدر: | Human Reproduction, 36(4), 1120-1133. Oxford University Press van der Kooi, A L L F, van Dijk, M, Broer, L, van den Berg, M H, Laven, J S E, van Leeuwen, F E, Lambalk, C B, Overbeek, A, Loonen, J J, van der Pal, H J, Tissing, W J, Versluys, B, Bresters, D, Beerendonk, C C M, Ronckers, C R, van der Heiden-van der Loo, M, Kaspers, G L, de Vries, A C H, Robison, L L, Hudson, M M, Chemaitilly, W, Byrne, J, Berger, C, Clemens, E, Dirksen, U, Falck Winther, J, Fosså, S D, Grabow, D, Haupt, R, Kaiser, M, Kepak, T, Kruseova, J, Modan-Moses, D, Pluijm, S M F, Spix, C, Zolk, O, Kaatsch, P, Krijthe, J H, Kremer, L C, Yasui, Y, Brooke, R J, Uitterlinden, A G, van den Heuvel-Eibrink, M M & van Dulmen-den Broeder, E 2021, ' Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function ', Human Reproduction, vol. 36, no. 4, pp. 1120-1133 . https://doi.org/10.1093/humrep/deaa342Test Human Reproduction (Oxford, England) Human Reproduction, 36, 4, pp. 1120-1133 Human Reproduction, 36, 1120-1133 van der Kooi, A-L L F, van Dijk, M, Broer, L, van den Berg, M H, Laven, J S E, van Leeuwen, F E, Lambalk, C B, Overbeek, A, Loonen, J J, van der Pal, H J, Tissing, W J, Versluys, B, Bresters, D, Beerendonk, C C M, Ronckers, C C R, van der Heiden-van der Loo, M, Kaspers, G L, de Vries, A C H, Robison, L L, Hudson, M M, Chemaitilly, W, Byrne, J, Berger, C, Clemens, E, Dirksen, U, Falck Winther, J, Fosså, S D, Grabow, D, Haupt, R, Kaiser, M, Kepak, T, Kruseova, J, Modan-Moses, D, Pluijm, S M F, Spix, C, Zolk, O, Kaatsch, P, Krijthe, J H, Kremer, L C, Yasui, Y, Brooke, R J, Uitterlinden, A G, van den Heuvel-Eibrink, M M & van Dulmen-den Broeder, E 2021, ' Possible modification of BRSK1 on the risk of alkylating chemotherapy-related reduced ovarian function ', Human Reproduction, vol. 36, no. 4, pp. 1120-1133 . https://doi.org/10.1093/humrep/deaa342Test |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Oncology, medicine.medical_treatment, Medizin, PANCARELIFE, Cohort Studies, ovarian reserve, 0302 clinical medicine, Fertility preservation, Child, media_common, fertility, biology, Rehabilitation, Intracellular Signaling Peptides and Proteins, Obstetrics and Gynecology, WOMEN, Anti-Müllerian hormone, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], 3. Good health, RESERVE, PREGNANCY, 030220 oncology & carcinogenesis, Cohort, Female, Cohort study, Adult, medicine.medical_specialty, MENOPAUSE, Anti-Mullerian Hormone/genetics, Adolescent, LONG-TERM, ANTI-MULLERIAN HORMONE, gonadotoxicity, Protein Serine-Threonine Kinases, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], 03 medical and health sciences, Ovarian function, All institutes and research themes of the Radboud University Medical Center, AGE, SDG 3 - Good Health and Well-being, FEMALE SURVIVORS, Internal medicine, Genetic model, medicine, media_common.cataloged_instance, Humans, childhood cancer, CHILDHOOD-CANCER SURVIVORS, European union, Ovarian reserve, Retrospective Studies, Chemotherapy, business.industry, Data Science, Ovary, Retrospective cohort study, Original Articles, Reproductive Genetics, AcademicSubjects/MED00905, 030104 developmental biology, Reproductive Medicine, biology.protein, business, survivorship |
| الوصف: | STUDY QUESTION 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)? SUMMARY ANSWER 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. WHAT IS KNOWN ALREADY 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. STUDY DESIGN, SIZE, DURATION CCS for the discovery cohort were identified from the Dutch Childhood Oncology Group (DCOG) LATER VEVO-study, a multi-centre retrospective cohort study evaluating fertility, ovarian reserve and risk of premature menopause among adult female 5-year survivors of childhood cancer. Female 5-year CCS, diagnosed with cancer and treated with chemotherapy before the age of 25 years, and aged 18 years or older at time of study were enrolled in the current study. Results from the discovery Dutch DCOG-LATER VEVO cohort (n = 285) were validated in the pan-European PanCareLIFE (n = 465) and the USA-based St. Jude Lifetime Cohort (n = 391). PARTICIPANTS/MATERIALS, SETTING, METHODS To evaluate ovarian function, anti-Müllerian hormone (AMH) levels were assessed in both the discovery cohort and the replication cohorts. Using additive genetic models in linear and logistic regression, five genetic variants involved in DNA damage response were analysed in relation to cyclophosphamide equivalent dose (CED) score and their impact on ovarian function. Results were then examined using fixed-effect meta-analysis. MAIN RESULTS AND THE ROLE OF CHANCE Meta-analysis across the three independent cohorts showed a significant interaction effect (P = 3.0 × 10−4) between rs11668344 of BRSK1 (allele frequency = 0.34) among CCS treated with high-dose alkylating agents (CED score ≥8000 mg/m2), resulting in a 2.5-fold increased odds of a reduced ovarian function (lowest AMH tertile) for CCS carrying one G allele compared to CCS without this allele (odds ratio genotype AA: 2.01 vs AG: 5.00). LIMITATIONS, REASONS FOR CAUTION While low AMH levels can also identify poor responders in assisted reproductive technology, it needs to be emphasized that AMH remains a surrogate marker of ovarian function. WIDER IMPLICATIONS OF THE FINDINGS Further research, validating our findings and identifying additional risk-contributing genetic variants, may enable individualized counselling regarding treatment-related risks and necessity of fertility preservation procedures in girls with cancer. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the PanCareLIFE project that has received funding from the European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602030. In addition, the DCOG-LATER VEVO study was funded by the Dutch Cancer Society (Grant no. VU 2006-3622) and by the Children Cancer Free Foundation (Project no. 20) and the St Jude Lifetime cohort study by NCI U01 CA195547. The authors declare no competing interests. TRIAL REGISTRATION NUMBER N/A. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0268-1161 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4ae7c525b5d2c7161af711da3873f478Test https://research.rug.nl/en/publications/063b1e16-52a7-45b0-b625-23f28047a5d1Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....4ae7c525b5d2c7161af711da3873f478 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 02681161 |
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