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dc.contributor.authorZhou, X
dc.contributor.authorWang, L
dc.contributor.authorXiao, J
dc.contributor.authorSun, J
dc.contributor.authorYu, L
dc.contributor.authorZhang, H
dc.contributor.authorMeng, X
dc.contributor.authorYuan, S
dc.contributor.authorTimofeeva, M
dc.contributor.authorLaw, PJ
dc.contributor.authorHoulston, RS
dc.contributor.authorDing, K
dc.contributor.authorDunlop, MG
dc.contributor.authorTheodoratou, E
dc.contributor.authorLi, X
dc.coverage.spatialUnited States
dc.date.accessioned2022-09-06T10:57:28Z
dc.date.available2022-09-06T10:57:28Z
dc.date.issued2022-07-01
dc.identifier.citationInternational Journal of Cancer, 2022, 151 (1), pp. 83 - 94en_US
dc.identifier.issn0020-7136
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5413
dc.identifier.eissn1097-0215
dc.identifier.eissn1097-0215
dc.identifier.doi10.1002/ijc.33945
dc.description.abstractAlcohol consumption is thought to be one of the modifiable risk factors for colorectal cancer (CRC). However, the causality and mechanisms by which alcohol exerts its carcinogenic effect are unclear. We evaluated the association between alcohol consumption and CRC risk by analyzing data from 32 cohort studies and conducted two-sample Mendelian randomization (MR) analysis to examine for casual relationship. To explore the effect of alcohol related DNA methylation on CRC risk, we performed an epigenetic MR analysis with data from an epigenome-wide association study (EWAS). We additionally performed gene-alcohol interaction analysis nested in the UK Biobank to assess effect modification between alcohol consumption and susceptibility genes. We discovered distinct effects of alcohol on CRC incidence and mortality from the meta-analyses, and genetic predisposition to alcohol drinking was causally associated with an increased CRC risk (OR = 1.79, 95% CI: 1.23-2.61) using two-sample MR approaches. In epigenetic MR analysis, two alcohol-related CpG sites (cg05593667 and cg10045354 mapped to COLCA1/COLCA2 gene) were identified causally associated with an increased CRC risk (P < 8.20 × 10-4 ). Gene-alcohol interaction analysis revealed that carriage of the risk allele of the eQTL (rs3087967) and mQTL (rs11213823) polymorphism of COLCA1/COLCA2 would interact with alcohol consumption to increase CRC risk (PInteraction  = .027 and PInteraction  = .016). Our study provides comprehensive evidence to elucidate the role of alcohol in CRC and highlights that the pathogenic effect of alcohol on CRC could be partly attributed to DNA methylation by regulating the expression of COLCA1/COLCA2 gene.
dc.formatPrint-Electronic
dc.format.extent83 - 94
dc.languageeng
dc.language.isoengen_US
dc.publisherWILEYen_US
dc.relation.ispartofInternational Journal of Cancer
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectDNA methylation
dc.subjectMendelian randomization
dc.subjectalcohol
dc.subjectcolorectal cancer
dc.subjectAlcohol Drinking
dc.subjectCohort Studies
dc.subjectColorectal Neoplasms
dc.subjectDNA Methylation
dc.subjectGenome-Wide Association Study
dc.subjectHumans
dc.subjectMendelian Randomization Analysis
dc.subjectNeoplasm Proteins
dc.subjectPolymorphism, Single Nucleotide
dc.titleAlcohol consumption, DNA methylation and colorectal cancer risk: Results from pooled cohort studies and Mendelian randomization analysis.en_US
dc.typeJournal Article
dcterms.dateAccepted2022-01-11
dc.date.updated2022-09-06T10:57:04Z
rioxxterms.versionVoRen_US
rioxxterms.versionofrecord10.1002/ijc.33945en_US
rioxxterms.licenseref.startdate2022-07-01
rioxxterms.typeJournal Article/Reviewen_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/35102554
pubs.issue1
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics
pubs.publication-statusPublished
pubs.publisher-urlhttp://dx.doi.org/10.1002/ijc.33945
pubs.volume151
icr.researchteamCancer Genomicsen_US
dc.contributor.icrauthorLaw, Philip
dc.contributor.icrauthorHoulston, Richard
icr.provenanceDeposited by Mr Arek Surman on 2022-09-06. Deposit type is initial. No. of files: 1. Files: Intl Journal of Cancer - 2022 - Zhou - Alcohol consumption DNA methylation and colorectal cancer risk Results from pooled.pdf


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