Evidence map›Paper›PMID 41912676›Full record

ArticleBritish journal of cancer2026

Natural menopause, menarche and breast cancer risk in BRCA1 and BRCA2 pathogenic variant carriers: a Mendelian randomization analysis.

Nasim Mavaddat, Daniel R Barnes, Kyriaki Michailidou, Emily Zhao, Debra Frost, Goska Leslie, Joe Dennis, Qin Wang, Manjeet K Bolla, EMBRACE and 6 more

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In one paragraph

Article in British journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Nasim MavaddatCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. nm274@medschl.cam.ac.uk.ORCID http://orcid.org/0000-0003-0307-055X
Daniel R BarnesCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-3781-7570
Kyriaki MichailidouDepartment of Biostatistics, The Cyprus Institute of Neurology & Genetics, Nicosia, Cyprus.ORCID http://orcid.org/0000-0001-7065-1237
Emily ZhaoCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Debra FrostCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Goska LeslieCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0001-5756-6222
Joe DennisCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-4591-1214
Qin WangCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Manjeet K BollaCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
EMBRACE
D Gareth EvansGenomic Medicine, Manchester Academic Health Sciences Centre, Division of Evolution, infection and genomic science, University of Manchester, Manchester University Hospitals NHS Foundation Trust, Manchester, UK.ORCID http://orcid.org/0000-0002-8482-5784
Marc TischkowitzDepartment of Genomic Medicine, Cambridge Biomedical Research Centre, National Institute for Health Research, University of Cambridge, Cambridge, UK.
Deborah J ThompsonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
John R B PerryMetabolic Research Laboratory, Wellcome-MRC Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.ORCID http://orcid.org/0000-0001-6483-3771
Antonis C AntoniouCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Douglas F EastonCentre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0003-2444-3247

Funding

Cancer Research UK (CRUK) A26886Cancer Research UK (CRUK) PPRPGM-Nov20\100002Cancer Research UK (CRUK) PRCPJT-Nov21\100004Cancer Research UK (CRUK) PRCPJT-Nov21\100004, A26886, PPRPGM-Nov20\100002DH | National Institute for Health Research (NIHR) NIHR203312DH | NIHR | Health Services Research Programme (NIHR Health Services Research Programme) NIHR203312
6 · The paper itself

Abstract

backgroundThe influence of age at menarche (AAM) and age at natural menopause (ANM) on breast cancer (BC) risk in BRCA1 and BRCA2 germline pathogenic variant (PV) carriers is uncertain. Observational studies are prone to bias and have limited statistical power. Mendelian randomization (MR) minimises bias and may be used to examine causal effects.

methodsTwo-sample and age-specific MR analyses for BC were performed. For AAM, two-sample multivariable MR and mediation analyses to account for the confounding effect of body mass index (BMI), were undertaken.

resultsGenetic scores for ANM and AAM predicted the respective traits in PV carriers. Inverse-variance weighted hazard ratios (HR) for genetically predicted ANM per-year were HR = 0.99 (95%CI:0.97-1.01, p = 0.45) and HR = 1.04 (95% CI:1.01-1.06, p = 0.003) for BRCA1 and BRCA2 PV carriers, respectively. After adjusting for genetic associations with BMI, AAM per-year on BC risk were HR = 0.90 (95%CI:0.83-0.98, p = 0.01) and HR = 0.95 (95%CI:0.86-1.04, p = 0.26) for BRCA1 and BRCA2 carriers, respectively, consistent with a protective effect of later AAM. DISCUSSION: MR analyses support causal associations between ANM and BC risk in BRCA2, but not BRCA1, and between AAM and BC risk in BRCA1 and BRCA2 PV carriers. These results may aid risk prediction models and genetic counselling of carriers.

Indexed as

BRCA1 ProteinBRCA2 ProteinBreast NeoplasmsMenarcheMenopauseBody Mass IndexFemaleGenetic Predisposition to DiseaseGerm-Line MutationHeterozygoteHumansMendelian Randomization AnalysisMiddle AgedRisk FactorsBRCA1 ProteinBRCA1 protein, humanBRCA2 ProteinBRCA2 protein, human

Identifiers

PMID41912676
PMCPMC13133355

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