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@ARTICLE{Fu:290043,
author = {R. Fu$^*$ and X. Chen$^*$ and T. Niedermaier$^*$ and T.
Seum$^*$ and M. Hoffmeister$^*$ and H. Brenner$^*$},
title = {{E}xcess weight, polygenic risk score and findings of
colorectal neoplasms at screening colonoscopy.},
journal = {The American journal of gastroenterology},
volume = {119},
number = {9},
issn = {0002-9270},
address = {Alphen aan den Rijn, The Netherlands},
publisher = {Wolters Kluwer Health, Inc.},
reportid = {DKFZ-2024-00948},
pages = {1913-1920},
year = {2024},
note = {#EA:C070#LA:C070#LA:C120# / 119(9), pp. 1913-1920 , 2024},
abstract = {Excess weight is an established risk factor for colorectal
cancer (CRC). However, evidence is lacking on how its impact
varies by polygenic risk at different stages of colorectal
carcinogenesis.We assessed the individual and joint
associations of body mass index (BMI) and polygenic risk
scores (PRSs) with findings of colorectal neoplasms among
4,784 participants of screening colonoscopy. Adjusted odds
ratios (aORs) for excess weight derived by multiple logistic
regression were converted to genetic risk equivalents (GREs)
to quantify the impact of excess weight compared to genetic
predisposition.Overweight and obesity (BMI 25-<30 and ≥30
kg/m2) were associated with increased risk of any colorectal
neoplasm (aOR $[95\%$ CI] 1.26 [1.09-1.45] and 1.47
[1.24-1.75]). Obesity was associated with increased risk of
advanced colorectal neoplasm (aOR $[95\%$ CI] 1.46
[1.16-1.84]). Dose-response relationships were seen for the
PRS (stronger for advanced neoplasms than any neoplasms),
with no interaction with BMI, suggesting multiplicative
effects of both factors. Obese participants with a PRS in
the highest tertile had a 2.3-fold $(95\%$ CI 1.7-3.1) and
2.9-fold $(95\%CI$ 1.9-4.3) increased risk of any colorectal
neoplasm and advanced colorectal neoplasm, respectively. The
aOR of obesity translated into a GRE of 38, meaning that its
impact was estimated to be equivalent to the risk caused by
38 percentiles higher PRS for colorectal neoplasm.Excess
weight and polygenic risk are associated with increased risk
of colorectal neoplasms in a multiplicative manner.
Maintaining normal weight is estimated to have an equivalent
effect as having 38 percentiles lower PRS.},
cin = {C070 / C120 / HD01},
ddc = {610},
cid = {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:38704818},
doi = {10.14309/ajg.0000000000002853},
url = {https://inrepo02.dkfz.de/record/290043},
}