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@ARTICLE{BarahonaPonce:163033,
author = {C. Barahona Ponce and D. Scherer and R. Brinster and F.
Boekstegers and K. Marcelain and V. Gárate and B. Müller
and G. de Toro and J. Retamales and O. Barajas and M.
Ahumada and E. Morales and A. Rojas and V. Sanhueza and D.
Loader and M. T. Rivera and L. Gutiérrez and G. Bernal and
A. Ortega and D. Montalvo and S. Portiño and M. E. Bertrán
and F. Gabler and L. Spencer and J. Olloquequi and C.
Fischer and M. Jenab and K. Aleksandrova and V. Katzke$^*$
and E. Weiderpass and C. Bonet and T. Moradi and K. Fischer
and W. Bossers and H. Brenner$^*$ and K. Hveem and N. Eklund
and U. Völker and M. Waldenberger and M. Fuentes Guajardo
and R. Gonzalez-Jose and G. Bedoya and M. C. Bortolini and
S. Canizales and C. Gallo and A. Ruiz Linares and F.
Rothhammer and J. Lorenzo Bermejo},
title = {{G}allstones, {B}ody {M}ass {I}ndex, {C}-reactive {P}rotein
and {G}allbladder {C}ancer - {M}endelian {R}andomization
{A}nalysis of {C}hilean and {E}uropean {G}enotype {D}ata.},
journal = {Hepatology},
volume = {73},
number = {5},
issn = {0270-9139},
address = {New York [u.a.]},
publisher = {Wiley Interscience},
reportid = {DKFZ-2020-01824},
pages = {1783-1796},
year = {2021},
note = {2021 May;73(5):1783-1796},
abstract = {Gallbladder cancer (GBC) is a neglected disease with
substantial geographical variability: Chile shows the
highest incidence worldwide, while GBC is relatively rare in
Europe. Here we investigate the causal effects of risk
factors considered in current GBC prevention programmes as
well as C-reactive protein (CRP) level as a marker of
chronic inflammation.We applied two-sample Mendelian
randomization (MR) using publicly available data and our own
data from a retrospective Chilean and a prospective European
study. Causality was assessed by inverse variance weighted
(IVW), MR-Egger regression and weighted median estimates
complemented with sensitivity analyses on potential
heterogeneity and pleiotropy, two-step MR and mediation
analysis. We found evidence for a causal effect of gallstone
disease on GBC risk in Chileans (p = 9 × 10-5 ) and
Europeans (p = 9 × 10-5 ). A genetically elevated body mass
index (BMI) increased GBC risk in Chileans (p = 0.03), while
higher CRP concentrations increased GBC risk in Europeans (p
= 4.1 × 10-6 ). European results suggest causal effects of
BMI on gallstone disease (p = 0.008); public Chilean data
were not, however, available to enable assessment of the
mediation effects among causal GBC risk factors.Two risk
factors considered in the current Chilean programme for GBC
prevention are causally linked to GBC risk: gallstones and
BMI. For Europeans, BMI showed a causal effect on gallstone
risk, which was itself causally linked to GBC risk.},
cin = {C020 / C070 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32893372},
doi = {10.1002/hep.31537.},
url = {https://inrepo02.dkfz.de/record/163033},
}