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000180479 1001_ $$0P:(DE-He78)c392ec8a090dcfbe801f135a6212caf9$$aChen, Xuechen$$b0$$eFirst author$$udkfz
000180479 245__ $$aAlcohol consumption, polygenic risk score, and early- and late-onset colorectal cancer risk.
000180479 260__ $$aAmsterdam$$bElsevier$$c2022
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000180479 520__ $$aEvidence 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).
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000180479 650_7 $$2Other$$aAlcohol consumption
000180479 650_7 $$2Other$$aCI, confidence interval
000180479 650_7 $$2Other$$aCRC, colorectal cancer
000180479 650_7 $$2Other$$aDACHS, Darmkrebs: Chancen der Verhütung durch Screening
000180479 650_7 $$2Other$$aEOCRC, early-onset colorectal cancer
000180479 650_7 $$2Other$$aEarly-onset colorectal cancer
000180479 650_7 $$2Other$$aGRE, genetic risk equivalent
000180479 650_7 $$2Other$$aGWAS, genome-wide association study
000180479 650_7 $$2Other$$aGenetic risk equivalentt
000180479 650_7 $$2Other$$aLOCRC, late-onset colorectal cancer
000180479 650_7 $$2Other$$aLate-onset colorectal cancer
000180479 650_7 $$2Other$$aNSAID, non-steroidal anti-inflammatory drug
000180479 650_7 $$2Other$$aOR, odds ratio
000180479 650_7 $$2Other$$aPRS, polygenic risk score
000180479 650_7 $$2Other$$aPolygenic risk score
000180479 650_7 $$2Other$$aSNP, single nucleotide polymorphisms
000180479 7001_ $$0P:(DE-He78)40c45b31a82f8311dd3a7363bd758720$$aLi, Hengjing$$b1$$udkfz
000180479 7001_ $$0P:(DE-He78)0311ebf3415e41860b4e2c56fbae6919$$aGuo, Feng$$b2$$udkfz
000180479 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b3$$udkfz
000180479 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b4$$eLast author$$udkfz
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