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Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study
LH. Schrijver, AC. Antoniou, H. Olsson, TM. Mooij, MJ. Roos-Blom, L. Azarang, J. Adlard, M. Ahmed, D. Barrowdale, R. Davidson, A. Donaldson, R. Eeles, DG. Evans, D. Frost, A. Henderson, L. Izatt, KR. Ong, V. Bonadona, I. Coupier, L. Faivre, JP....
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem
Grantová podpora
10118
Cancer Research UK - United Kingdom
C12292/A20861
Cancer Research UK - United Kingdom
C12292/A11174
Cancer Research UK - United Kingdom
- MeSH
- dospělí MeSH
- genetická predispozice k nemoci MeSH
- kohortové studie MeSH
- kontraceptiva orální aplikace a dávkování MeSH
- lidé středního věku MeSH
- lidé MeSH
- mutace * MeSH
- nádory vaječníků epidemiologie genetika prevence a kontrola MeSH
- následné studie MeSH
- proporcionální rizikové modely MeSH
- protein BRCA1 genetika MeSH
- protein BRCA2 genetika MeSH
- retrospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa MeSH
BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.
Cancer Epidemiology Division Cancer Council Victoria Melbourne Victoria Australia
Centre Hospitalier Universitaire de Montpellier Hôpital Arnaud de Villeneuve Montpellier France
Centre Léon Bérard Unité de Prévention et Epidémiologie Génétique Lyon France
Centre National de la Recherche Scientifique Unités Mixtes de Recherche Lyon France
Centro de Investigación Biomédica en Red de Enfermedades Raras Madrid Spain
Clinical Genetics Guy's and St Thomas' NHS Foundation Trust London United Kingdom
Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute Brno Czech Republic
Department of Clinical Genetics Karolinska University Hospital Stockholm Sweden
Department of Clinical Genetics Rigshospitalet København Denmark
Department of Clinical Genetics South Glasgow University Hospitals Glasgow United Kingdom
Department of Clinical Genetics St Michael's Hospital Bristol United Kingdom
Department of Dermatology University of Utah School of Medicine Salt Lake City UT
Department of Epidemiology Mailman School of Public Health Columbia University New York NY
Department of Epidemiology Netherlands Cancer Institute Amsterdam the Netherlands
Department of Genetics and Pathology Pomeranian Medical University Szczecin Poland
Department of Medical Oncology Peter MacCallum Cancer Centre Victoria Australia
Department of Molecular Genetics National Institute of Oncology Budapest Hungary
Department of Oncology Lund University Hospital Lund Sweden
Department of Oncology Peter MacCallum Cancer Centre University of Melbourne Parkville Australia
Division of Oncology and Pathology Department of Clinical Sciences Lund Lund University Lund Sweden
Family Cancer Clinic Netherlands Cancer Institute Amsterdam the Netherlands
Human Genetics Group Centro Nacional De Investigaciones Oncologicas Madrid Spain
Institut National de la Santé et de la Recherche Médicale Paris France
Institute for Medical Informatics Statistics and Epidemiology University of Leipzig Germany
Medical Faculty University of Cologne and University Hospital Cologne Cologne Germany
Mines ParisTech Fontainebleau Paris France
Oncogenetics Team The Institute of Cancer Research London United Kingdom
Paris Sciences et Lettres University Paris France
Service d'Oncogénétique Régional Poitou Charentes Centre Hospitalier Georges Renon Niort France
Service de Génétique médicale et Oncogénétique Montpellier France
Unité d' Oncogénétique Centre Paul Strauss Strasbourg France
Unité d'Oncogénétique Centre de Lutte Contre le Cancer Georges François Leclerc Dijon France
Université Claude Bernard Lyon 1 Villeurbanne France
Yorkshire Regional Genetics Service Chapel Allerton Hospital Leeds United Kingdom
Citace poskytuje Crossref.org
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- $a Oral contraceptive use and ovarian cancer risk for BRCA1/2 mutation carriers: an international cohort study / $c LH. Schrijver, AC. Antoniou, H. Olsson, TM. Mooij, MJ. Roos-Blom, L. Azarang, J. Adlard, M. Ahmed, D. Barrowdale, R. Davidson, A. Donaldson, R. Eeles, DG. Evans, D. Frost, A. Henderson, L. Izatt, KR. Ong, V. Bonadona, I. Coupier, L. Faivre, JP. Fricker, P. Gesta, K. van Engelen, A. Jager, FH. Menko, MJE. Mourits, CF. Singer, YY. Tan, L. Foretova, M. Navratilova, RK. Schmutzler, C. Ellberg, AM. Gerdes, T. Caldes, J. Simard, E. Olah, A. Jakubowska, J. Rantala, A. Osorio, JL. Hopper, KA. Phillips, RL. Milne, M. Beth Terry, C. Noguès, C. Engel, K. Kast, DE. Goldgar, FE. van Leeuwen, DF. Easton, N. Andrieu, MA. Rookus, Epidemiological Study of Familial Breast Cancer, Gene Etude Prospective Sein Ovaire Sein, Hereditary Breast and Ovarian Cancer Research Group Netherlands, and International BRCA1/2 Carrier Cohort Study
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- $a BACKGROUND: Ovarian cancer risk in BRCA1 and BRCA2 mutation carriers has been shown to decrease with longer duration of oral contraceptive use. Although the effects of using oral contraceptives in the general population are well established (approximately 50% risk reduction in ovarian cancer), the estimated risk reduction in mutation carriers is much less precise because of potential bias and small sample sizes. In addition, only a few studies on oral contraceptive use have examined the associations of duration of use, time since last use, starting age, and calendar year of start with risk of ovarian cancer. OBJECTIVE: This study aimed to investigate in more detail the associations of various characteristics of oral contraceptive use and risk of ovarian cancer, to provide healthcare providers and carriers with better risk estimates. STUDY DESIGN: In this international retrospective study, ovarian cancer risk associations were assessed using oral contraceptives data on 3989 BRCA1 and 2445 BRCA2 mutation carriers. Age-dependent-weighted Cox regression analyses were stratified by study and birth cohort and included breast cancer diagnosis as a covariate. To minimize survival bias, analyses were left truncated at 5 years before baseline questionnaire. Separate analyses were conducted for each aspect of oral contraceptive use and in a multivariate analysis, including all these aspects. In addition, the analysis of duration of oral contraceptive use was stratified by recency of use. RESULTS: Oral contraceptives were less often used by mutation carriers who were diagnosed with ovarian cancer (ever use: 58.6% for BRCA1 and 53.5% BRCA2) than by unaffected carriers (ever use: 88.9% for BRCA1 and 80.7% for BRCA2). The median duration of use was 7 years for both BRCA1 and BRCA2 carriers who developed ovarian cancer and 9 and 8 years for unaffected BRCA1 and BRCA2 carriers with ovarian cancer, respectively. For BRCA1 mutation carriers, univariate analyses have shown that both a longer duration of oral contraceptive use and more recent oral contraceptive use were associated with a reduction in the risk of ovarian cancer. However, in multivariate analyses, including duration of use, age at first use, and time since last use, duration of oral contraceptive use proved to be the prominent protective factor (compared with <5 years: 5-9 years [hazard ratio, 0.67; 95% confidence interval, 0.40-1.12]; >10 years [hazard ratio, 0.37; 95% confidence interval, 0.19-0.73]; Ptrend=.008). The inverse association between duration of use and ovarian cancer risk persisted for more than 15 years (duration of ≥10 years; BRCA1 <15 years since last use [hazard ratio, 0.24; 95% confidence interval, 0.14-0.43]; BRCA1 >15 years since last use [hazard ratio, 0.56; 95% confidence interval, 0.18-0.59]). Univariate results for BRCA2 mutation carriers were similar but were inconclusive because of limited sample size. CONCLUSION: For BRCA1 mutation carriers, longer duration of oral contraceptive use is associated with a greater reduction in ovarian cancer risk, and the protection is long term.
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