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@ARTICLE{Verdiesen:300349,
author = {R. M. G. Verdiesen and M. Shokouhi and S. Burgess and S.
Canisius and J. Chang-Claude$^*$ and S. E. Bojesen and M. K.
Schmidt},
title = {{C}ausal effects of breast cancer risk factors across
hormone receptor breast cancer subtypes: {A} two-sample
{M}endelian randomization study.},
journal = {Cancer epidemiology, biomarkers $\&$ prevention},
volume = {34},
number = {6},
issn = {1055-9965},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2025-00783},
pages = {933-943},
year = {2025},
note = {2025 Jun 3;34(6):933-943},
abstract = {It is unclear if established breast cancer risk factors
exert similar causal effects across hormone receptor breast
cancer subtypes. We estimated and compared causal estimates
of height, body mass index (BMI), type 2 diabetes, age at
menarche, age at menopause, breast density, alcohol
consumption, regular smoking, and physical activity across
these subtypes.We used a two-sample Mendelian randomization
approach and selected genetic instrumental variables from
large-scale GWAS. Publicly available summary-level BCAC data
(n = 247,173; 133,384 cases, 113,789 controls) for the
following subtypes were included: luminal A-like (45,253
cases); luminal B/HER2-negative-like (6,350 cases); luminal
B-like (6,427 cases); HER2-enriched-like (2,884 cases);
triple negative (8,602 cases). We employed multiple MR
methods to evaluate the strength of causal evidence for each
risk factor-subtype association.Collectively, our analyses
indicated that increased height and decreased BMI are
probable causal risk factors for all five subtypes. For the
other risk factors, the strength of evidence for causal
effects differed across subtypes. Heterogeneity in the
magnitude of causal effect estimates for age at menopause
and breast density was explained by null findings for triple
negative tumours. Regular smoking was the sole risk factor
for which there was no evidence for a causal effect on any
subtype.This study suggests that established breast cancer
risk factors differ across hormone receptor subtypes.Our
results are valuable for the development of primary
prevention strategies, improvement of breast cancer risk
stratification in the general population, and for the
identification of novel breast cancer risk factors.},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40214978},
doi = {10.1158/1055-9965.EPI-24-1440},
url = {https://inrepo02.dkfz.de/record/300349},
}