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@ARTICLE{Chen:186453,
author = {X. Chen$^*$ and H. Li$^*$ and M. Mandic$^*$ and M.
Hoffmeister$^*$ and H. Brenner$^*$},
title = {{A}ssessment of {B}ody {M}ass {I}ndex, {P}olygenic {R}isk
{S}core, and {D}evelopment of {C}olorectal {C}ancer.},
journal = {JAMA network open},
volume = {5},
number = {12},
issn = {2574-3805},
address = {Chicago, Ill.},
publisher = {American Medical Association},
reportid = {DKFZ-2022-03174},
pages = {e2248447 -},
year = {2022},
note = {#EA:C070#LA:C070#LA:C120#},
abstract = {Excess weight, the prevalence of which is high and
increasing in many countries, is linked to multiple adverse
health outcomes, including increased colorectal cancer (CRC)
risk. Better communication of health risks associated with
excess weight might support efforts of prevention.To
evaluate the individual and joint associations of body mass
index (BMI) and polygenic risk with CRC, to assess potential
interactions among them, and to quantify by how much
increased polygenic risk for CRC can be offset by having a
BMI within reference range.This population-based
case-control study was conducted in the Rhine-Neckar region
of southwest Germany, with recruitment from 2003 to 2017.
Participants with both risk factor and genetic information
were included for analysis. Data analysis was conducted from
December 8, 2021, to February 17, 2022.BMI was calculated as
self-reported weight in kilograms approximately 10 years
before diagnosis or interview and current height in meters
squared. A polygenic risk score (PRS) was built based on 140
CRC-related risk loci.Individual and joint associations of
BMI and PRS with CRC were estimated using multiple logistic
regression. Associations of excess weight with CRC were
quantified by adjusted odds ratios (aORs) and genetic risk
equivalents (GREs), the equivalent outcomes conveyed by
defined differences in PRS percentiles.Among 9169
participants (median [IQR] age, 69 [62-76] years; 5589
$[61.0\%]$ male participants) included, 5053 had CRC and
4116 did not. BMI of 30 or greater was associated with
higher odds of having CRC compared with BMI less than 25
(aOR, 1.71; $95\%$ CI, 1.49-1.97), independent of PRS levels
(P for interaction = .45). Participants with BMI of 30 or
greater and a PRS in the highest tertile had higher odds of
CRC compared with participants with BMI less than 25 and a
PRS in the lowest tertile (aOR, 3.82; $95\%$ CI, 3.03-4.82).
The estimated association of BMI greater than 30 with CRC
risk was equivalent to that of having a 41 $(95\%$ CI,
29-53)-percentile higher PRS. BMI of 30 or greater was
particularly associated with stage IV CRC (aOR, 2.21; $95\%$
CI, 1.71-2.84).These findings suggest that excess weight was
associated with CRC regardless of PRS levels. The
association of having a BMI within reference range may be
similar to that of having a substantially lower polygenic
risk for CRC.},
keywords = {Humans / Male / Aged / Female / Body Mass Index /
Case-Control Studies / Risk Factors / Weight Gain /
Colorectal Neoplasms: epidemiology / Colorectal Neoplasms:
genetics},
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:36547977},
doi = {10.1001/jamanetworkopen.2022.48447},
url = {https://inrepo02.dkfz.de/record/186453},
}