Theodora C van Tilborg1, Frank J Broekmans, Anouk Pijpe, Lieske H Schrijver, Thea M Mooij, Jan C Oosterwijk, Senno Verhoef, Encarna B Gómez Garcia, Wendy A van Zelst-Stams, Muriel A Adank, Christi J van Asperen, Helena C van Doorn, Theo A van Os, Anna M Bos, Matti A Rookus, Margreet G Ausems. 1. 1Department of Reproductive Medicine 2Department of Medical Genetics, University Medical Center Utrecht, Utrecht, The Netherlands 3Department of Epidemiology 4Family Cancer Clinic, Netherlands Cancer Institute, Amsterdam, The Netherlands 5Department of Genetics, Groningen University, University Medical Center, Groningen, The Netherlands 6Department of Clinical Genetics, Maastricht University Medical Center, Maastricht, The Netherlands 7GROW, School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands 8Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands 9Department of Clinical Genetics, VU University Medical Centre, Amsterdam, The Netherlands 10Department of Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands 11Department of Obstetrics and Gynaecology, Division of Gynaecology Oncology, Erasmus University Medical Center, Rotterdam, The Netherlands 12Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Abstract
OBJECTIVE: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. METHODS: Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. RESULTS: A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. CONCLUSIONS: Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.
OBJECTIVE: It has been hypothesized that BRCA1/2 mutation carriers have an earlier age at natural menopause (ANM), although to date findings are inconclusive. This study assessed the influence of BRCA mutation status on ANM, and aimed to explore the reasons of inconsistency in the literature. METHODS: Cross-sectional assessment from an ongoing nationwide cohort study among members of BRCA1/2 mutated families. Information was obtained by a standardized questionnaire. Kaplan-Meier curves were constructed, and Cox regression was used to assess the association between BRCA1/2 mutation status and ANM. Adjustments were made for birth cohort, family, smoking, use of hormonal contraceptives, and parity. RESULTS: A total of 1,208 BRCA1/2 mutation carriers and 2,211 proven noncarriers were included. Overall, no association was found between BRCA1/2 mutation status and ANM (adjusted hazard ratio [HR] = 1.06 [95% CI, 0.87-1.30]). We examined if the null finding was due to informative censoring by uptake of risk-reducing salpingo-oophorectomy. Indeed, within the oldest birth cohort, in which the percentage of surgical menopause events was lowest and comparable between carriers and noncarriers, the HR for earlier natural menopause in carriers was 1.45 (95% CI, 1.09-1.94). The second oldest birth cohort, however, demonstrated a decreased HR (0.67 [95% CI, 0.46-0.98]), and thus no trend over birth cohorts was found. CONCLUSIONS: Various types of selection bias hamper the comparison of ANM between BRCA1/2 mutation carriers and noncarriers, genetically tested in the clinic.
Authors: Drechsel Katja C E; van Tilborg Theodora C; Eijkemans Marinus J C; Lentjes Eef G W M; Homminga Irene; Goddijn Mariette; van Golde Ron J T; Verpoest Willem; Lichtenbelt Klaske D; Broekmans Frank J M; Bos Anna M E Journal: Reprod Sci Date: 2022-06-15 Impact factor: 3.060
Authors: I A P Derks-Smeets; T C van Tilborg; A van Montfoort; L Smits; H L Torrance; M Meijer-Hoogeveen; F Broekmans; J C F M Dreesen; A D C Paulussen; V C G Tjan-Heijnen; I Homminga; M M J van den Berg; M G E M Ausems; M de Rycke; C E M de Die-Smulders; W Verpoest; R van Golde Journal: J Assist Reprod Genet Date: 2017-08-22 Impact factor: 3.412
Authors: Łukasz Kępczyński; Katarzyna Połatyńska; Anna Nykel; Jordan Sałamunia; Tadeusz Kałużewski; Andrzej Kużawczyk; Agnieszka Gach Journal: Prz Menopauzalny Date: 2021-01-07
Authors: Nasim Mavaddat; Antonis C Antoniou; Thea M Mooij; Maartje J Hooning; Bernadette A Heemskerk-Gerritsen; Catherine Noguès; Marion Gauthier-Villars; Olivier Caron; Paul Gesta; Pascal Pujol; Alain Lortholary; Daniel Barrowdale; Debra Frost; D Gareth Evans; Louise Izatt; Julian Adlard; Ros Eeles; Carole Brewer; Marc Tischkowitz; Alex Henderson; Jackie Cook; Diana Eccles; Klaartje van Engelen; Marian J E Mourits; Margreet G E M Ausems; Linetta B Koppert; John L Hopper; Esther M John; Wendy K Chung; Irene L Andrulis; Mary B Daly; Saundra S Buys; Javier Benitez; Trinidad Caldes; Anna Jakubowska; Jacques Simard; Christian F Singer; Yen Tan; Edith Olah; Marie Navratilova; Lenka Foretova; Anne-Marie Gerdes; Marie-José Roos-Blom; Flora E Van Leeuwen; Brita Arver; Håkan Olsson; Rita K Schmutzler; Christoph Engel; Karin Kast; Kelly-Anne Phillips; Mary Beth Terry; Roger L Milne; David E Goldgar; Matti A Rookus; Nadine Andrieu; Douglas F Easton Journal: Breast Cancer Res Date: 2020-01-16 Impact factor: 6.466