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@ARTICLE{Hua:168784,
author = {X. Hua and J. Y. Dai and S. Lindström and T. A. Harrison
and Y. Lin and S. R. Alberts and E. Alwers$^*$ and S. I.
Berndt and H. Brenner$^*$ and D. D. Buchanan and P. T.
Campbell and G. Casey and J. Chang-Claude$^*$ and S.
Gallinger and G. G. Giles and R. M. Goldberg and M. J.
Gunter and M. Hoffmeister$^*$ and M. A. Jenkins and A. D.
Joshi and W. Ma and R. L. Milne and N. Murphy and R. K. Pai
and L. C. Sakoda and R. E. Schoen and Q. Shi and M. L.
Slattery and M. Song and E. White and L. Le Marchand and A.
T. Chan and U. Peters and P. A. Newcomb},
title = {{G}enetically predicted circulating {C}-reactive protein
concentration and colorectal cancer survival: {A}
{M}endelian randomization consortium study.},
journal = {Cancer epidemiology, biomarkers $\&$ prevention},
volume = {30},
number = {7},
issn = {1538-7755},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2021-01065},
pages = {1349-1358},
year = {2021},
note = {2021 Jul;30(7):1349-1358},
abstract = {A positive association between circulating C-reactive
protein (CRP) and colorectal cancer (CRC) survival was
reported in observational studies, which are susceptible to
unmeasured confounding and reverse causality. We used a
Mendelian randomization approach to evaluate the association
between genetically-predicted CRP concentrations and
CRC-specific survival.We used individual-level data for
16,918 eligible CRC cases of European ancestry from 15
studies within the International Survival Analysis of
Colorectal Cancer Consortium. We calculated a genetic risk
score based on 52 CRP-associated genetic variants identified
from genome-wide association studies. Due to the
non-collapsibility of hazard ratios from Cox proportional
hazards models, we used the additive hazards model to
calculate hazard differences (HD) and $95\%$ confidence
intervals (CI) for the association between
genetically-predicted CRP concentrations and CRC-specific
survival, overall and by stage at diagnosis and tumor
location. Analyses were adjusted for age at diagnosis, sex,
body mass index, genotyping platform, study, and principal
components.Of the 5,395 $(32\%)$ deaths accrued over up to
10 years of follow-up, 3,808 $(23\%)$ were due to CRC.
Genetically-predicted CRP concentration was not associated
with CRC-specific survival (HD= -1.15, $95\%$ CI: -2.76 to
0.47 per 100,000 person-years, P =0.16). Similarly, no
associations were observed in subgroup analyses by stage at
diagnosis or tumor location.Despite adequate power to detect
moderate associations, our results did not support a causal
effect of circulating CRP concentrations on CRC-specific
survival.Future research evaluating genetically-determined
levels of other circulating inflammatory biomarkers (i.e.
interleukin-6) with CRC survival outcomes is needed.},
cin = {C070 / C120 / C020 / HD01},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)C020-20160331 / 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:33972368},
doi = {10.1158/1055-9965.EPI-20-1848},
url = {https://inrepo02.dkfz.de/record/168784},
}