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@ARTICLE{Chen:180479,
author = {X. Chen$^*$ and H. Li$^*$ and F. Guo$^*$ and M.
Hoffmeister$^*$ and H. Brenner$^*$},
title = {{A}lcohol consumption, polygenic risk score, and early- and
late-onset colorectal cancer risk.},
journal = {EClinicalMedicine},
volume = {49},
issn = {2589-5370},
address = {Amsterdam},
publisher = {Elsevier},
reportid = {DKFZ-2022-01358},
pages = {101460},
year = {2022},
note = {#EA:C070#LA:C070#LA:C120#},
abstract = {Evidence is lacking on the impact of alcohol consumption on
colorectal cancer (CRC) risk (overall and by age at
diagnosis) by polygenic risk score (PRS) levels, and it is
unclear how the magnitude of CRC risk associated with
alcohol consumption compares to the magnitude of genetically
determined risk.Multiple logistic regression was used to
assess the association between alcohol consumption and
colorectal cancer (CRC) across PRS levels based on 140
CRC-related loci among 5104 CRC cases and 4131 controls from
a large population-based case-control study. We compared the
effects for alcohol consumption and PRS on CRC risk using
the 'Genetic Risk Equivalent (GRE)' for effective risk
communication. Specific analyses were conducted for
early-onset CRC (EOCRC, <55 years) and late-onset CRC
(LOCRC, ≥55 years).High alcohol consumption, and to a
lower extent, also alcohol abstinence were associated with
increased CRC risk. Compared to low alcohol consumption
(0·1-<25 g/d), lifetime average alcohol consumption ≥25
g/d was more strongly associated with EOCRC [odds ratio (OR)
1·8, $95\%$ confidence interval (CI) 1·2-2·8] than with
LOCRC risk (OR 1·3, $95\%$ CI 1·1-1·4) (P-value for
interaction with age =0·011). Interactions between alcohol
consumption and PRS did not reach statistical significance
for either EOCRC or LOCRC risk. The estimated impact of high
lifetime alcohol consumption on EOCRC was equivalent to the
effect of having 47 percentiles higher PRS (GRE 47, $95\%$
CI 12-82), stronger than the impact on LOCRC (GRE 18, $95\%$
CI 8-29).Excessive alcohol use was strongly associated with
EOCRC risk, independent of PRS levels. Abstaining from heavy
drinking could reduce risk for CRC, in particular for EOCRC
to an extent that would be equivalent to having a much lower
genetically determined risk.The first author (X.C.) was
supported by the Guangzhou Elite Project (GEP). The DACHS
study was supported by grants from the German Research
Council (BR 1704/6-1, BR1704/6-3, BR 1704/6-4, BR 1704/6-6,
CH 117/1-1, BR 1704/17-1, HO 5117/2-1) and the German
Federal Ministry of Education and Research (01KH0404,
01ER0814, 01ER0815, 01GL1712).},
keywords = {Alcohol consumption (Other) / CI, confidence interval
(Other) / CRC, colorectal cancer (Other) / DACHS, Darmkrebs:
Chancen der Verhütung durch Screening (Other) / EOCRC,
early-onset colorectal cancer (Other) / Early-onset
colorectal cancer (Other) / GRE, genetic risk equivalent
(Other) / GWAS, genome-wide association study (Other) /
Genetic risk equivalentt (Other) / LOCRC, late-onset
colorectal cancer (Other) / Late-onset colorectal cancer
(Other) / NSAID, non-steroidal anti-inflammatory drug
(Other) / OR, odds ratio (Other) / PRS, polygenic risk score
(Other) / Polygenic risk score (Other) / SNP, single
nucleotide polymorphisms (Other)},
cin = {C070 / HD01 / C120},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)HD01-20160331 /
I:(DE-He78)C120-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:35747198},
pmc = {pmc:PMC9126769},
doi = {10.1016/j.eclinm.2022.101460},
url = {https://inrepo02.dkfz.de/record/180479},
}