{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T12:05:37Z","timestamp":1770293137399,"version":"3.49.0"},"reference-count":45,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T00:00:00Z","timestamp":1518134400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA122839 and R01 CA143237"],"award-info":[{"award-number":["U01 CA122839 and R01 CA143237"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"crossref","award":["U01\/U24 CA074783 and U01\/U24 CA074794"],"award-info":[{"award-number":["U01\/U24 CA074783 and U01\/U24 CA074794"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C588\/A19167"],"award-info":[{"award-number":["C588\/A19167"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["UM1 CA167551-NIH-CCFR"],"award-info":[{"award-number":["UM1 CA167551-NIH-CCFR"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA074778 and U01\/U24 CA097735"],"award-info":[{"award-number":["U01 CA074778 and U01\/U24 CA097735"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0192223","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T13:52:40Z","timestamp":1518184360000},"page":"e0192223","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Interaction between polymorphisms in aspirin metabolic pathways, regular aspirin use and colorectal cancer risk: A case-control study in unselected white European populations"],"prefix":"10.1371","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9626-0971","authenticated-orcid":true,"given":"Harsh","family":"Sheth","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Northwood","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelia M.","family":"Ulrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominique","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faye","family":"Elliott","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer H.","family":"Barrett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Forman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Roland","family":"Wolf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael S.","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro","family":"Santibanez-Koref","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Haile","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham","family":"Casey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Jenkins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aung Ko","family":"Win","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John L.","family":"Hopper","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loic Le","family":"Marchand","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Noralane M.","family":"Lindor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen N.","family":"Thibodeau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John D.","family":"Potter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Burn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. Timothy","family":"Bishop","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2018,2,9]]},"reference":[{"issue":"5","key":"ref1","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1016\/S1470-2045(12)70112-2","article-title":"Effects of regular aspirin on long-term cancer incidence and metastasis: a systematic comparison of evidence from observational studies versus randomised trials","volume":"13","author":"AM Algra","year":"2012","journal-title":"The Lancet Oncology"},{"issue":"2","key":"ref2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.7326\/0003-4819-159-2-201307160-00002","article-title":"Alternate-day, low-dose aspirin and cancer risk: long-term observational follow-up of a randomized trial","volume":"159","author":"NR Cook","year":"2013","journal-title":"Annals of internal medicine"},{"issue":"9826","key":"ref3","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1016\/S0140-6736(11)61720-0","article-title":"Short-term effects of daily aspirin on cancer incidence, mortality, and non-vascular death: analysis of the time course of risks and benefits in 51 randomised controlled trials","volume":"379","author":"PM Rothwell","year":"2012","journal-title":"The Lancet"},{"issue":"9809","key":"ref4","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/S0140-6736(11)61049-0","article-title":"Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial","volume":"378","author":"J Burn","year":"2011","journal-title":"The Lancet"},{"issue":"3","key":"ref5","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1038\/nrc.2016.4","article-title":"Aspirin and colorectal cancer: the promise of precision chemoprevention","volume":"16","author":"DA Drew","year":"2016","journal-title":"Nat Rev Cancer"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/carcin\/bgs296","article-title":"IkappaBKbeta and NFkappaB1, NSAID use and risk of colorectal cancer in the Colon Cancer Family Registry","volume":"34","author":"BL Seufert","year":"2013","journal-title":"Carcinogenesis"},{"issue":"5","key":"ref7","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/nrclinonc.2011.199","article-title":"The role of aspirin in cancer prevention","volume":"9","author":"MJ Thun","year":"2012","journal-title":"Nat Rev Clin Oncol"},{"issue":"8","key":"ref8","doi-asserted-by":"crossref","first-page":"2303","DOI":"10.1158\/1078-0432.CCR-07-4599","article-title":"Ornithine decarboxylase G316A genotype is prognostic for colorectal adenoma recurrence and predicts efficacy of aspirin chemoprevention","volume":"14","author":"RA Hubner","year":"2008","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"issue":"3","key":"ref9","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1158\/1055-9965.EPI-04-0510","article-title":"PTGS2 (COX-2) -765G > C promoter variant reduces risk of colorectal adenoma among nonusers of nonsteroidal anti-inflammatory drugs","volume":"14","author":"CM Ulrich","year":"2005","journal-title":"Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"},{"issue":"1","key":"ref10","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1158\/1055-9965.EPI-15-0697","article-title":"Aspirin Reduces Plasma Concentrations of the Oncometabolite 2-Hydroxyglutarate: Results of a Randomized, Double-Blind, Crossover Trial","volume":"25","author":"DB Liesenfeld","year":"2016","journal-title":"Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"},{"issue":"11","key":"ref11","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1001\/jama.2015.1815","article-title":"Association of aspirin and non-steroidal anti-inflammatory drug use with risk of colorectal cancer according to genetic variants","volume":"313","author":"H Nan","year":"2015","journal-title":"Jama"},{"issue":"7","key":"ref12","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1002\/gcc.22167","article-title":"Genetic variation in UGT genes modify the associations of NSAIDs with risk of colorectal cancer: colon cancer family registry","volume":"53","author":"D Scherer","year":"2014","journal-title":"Genes Chromosomes Cancer"},{"issue":"24","key":"ref13","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1093\/jnci\/djt331","article-title":"Aspirin use, 8q24 single nucleotide polymorphism rs6983267, and colorectal cancer according to CTNNB1 alterations","volume":"105","author":"H Nan","year":"2013","journal-title":"J Natl Cancer Inst"},{"issue":"12","key":"ref14","doi-asserted-by":"crossref","first-page":"2059","DOI":"10.1007\/s10552-013-0282-1","article-title":"COX-1 (PTGS1) and COX-2 (PTGS2) polymorphisms, NSAID interactions, and risk of colon and rectal cancers in two independent populations","volume":"24","author":"KW Makar","year":"2013","journal-title":"Cancer Causes Control"},{"issue":"5","key":"ref15","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1002\/gcc.22042","article-title":"Genetic variation in the lipoxygenase pathway and risk of colorectal neoplasia","volume":"52","author":"SE Kleinstein","year":"2013","journal-title":"Genes Chromosomes Cancer"},{"issue":"12","key":"ref16","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1158\/1940-6207.CAPR-11-0300","article-title":"Variants downstream of the ornithine decarboxylase gene influence risk of colorectal adenoma and aspirin chemoprevention","volume":"4","author":"EL Barry","year":"2011","journal-title":"Cancer prevention research (Philadelphia, Pa)"},{"issue":"9","key":"ref17","first-page":"3566","article-title":"CYP2C9 and UGT1A6 genotypes modulate the protective effect of aspirin on colon adenoma risk","volume":"61","author":"J Bigler","year":"2001","journal-title":"Cancer research"},{"issue":"11","key":"ref18","doi-asserted-by":"crossref","first-page":"2331","DOI":"10.1158\/1055-9965.EPI-07-0648","article-title":"Colon Cancer Family Registry: an international resource for studies of the genetic epidemiology of colon cancer","volume":"16","author":"PA Newcomb","year":"2007","journal-title":"Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"},{"issue":"2","key":"ref19","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1093\/carcin\/24.2.275","article-title":"Investigation of interaction between N-acetyltransferase 2 and heterocyclic amines as potential risk factors for colorectal cancer","volume":"24","author":"JH Barrett","year":"2003","journal-title":"Carcinogenesis"},{"issue":"Suppl 1","key":"ref20","doi-asserted-by":"crossref","first-page":"S26","DOI":"10.1093\/ije\/26.suppl_1.S26","article-title":"Pilot phase studies on the accuracy of dietary intake measurements in the EPIC project: overall evaluation of results. European Prospective Investigation into Cancer and Nutrition","volume":"26","author":"R Kaaks","year":"1997","journal-title":"International journal of epidemiology"},{"issue":"6","key":"ref21","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/gcc.22157","article-title":"The effect of UGT1A and UGT2B polymorphisms on colorectal cancer risk: Haplotype associations and gene\u2013environment interactions","volume":"53","author":"AY Angstadt","year":"2014","journal-title":"Genes, Chromosomes and Cancer"},{"issue":"8","key":"ref22","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1097\/FPC.0b013e3283631784","article-title":"Impact of genetic polymorphisms on adenoma recurrence and toxicity in a COX2 inhibitor (celecoxib) trial: results from a pilot study","volume":"23","author":"S Kraus","year":"2013","journal-title":"Pharmacogenetics and genomics"},{"issue":"10","key":"ref23","doi-asserted-by":"crossref","first-page":"2726","DOI":"10.1158\/1055-9965.EPI-09-0363","article-title":"Cyclooxygenase-2 polymorphisms, aspirin treatment, and risk for colorectal adenoma recurrence\u2014data from a randomized clinical trial","volume":"18","author":"EL Barry","year":"2009","journal-title":"Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"},{"issue":"40","key":"ref24","doi-asserted-by":"crossref","first-page":"34820","DOI":"10.1074\/jbc.M111.267161","article-title":"Intracellular erythrocyte platelet-activating factor acetylhydrolase I inactivates aspirin in blood","volume":"286","author":"G Zhou","year":"2011","journal-title":"The Journal of biological chemistry"},{"issue":"10","key":"ref25","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1124\/dmd.105.005587","article-title":"Functional characterization of three naturally occurring single nucleotide polymorphisms in the CES2 gene encoding carboxylesterase 2 (HCE-2)","volume":"33","author":"T Kubo","year":"2005","journal-title":"Drug metabolism and disposition: the biological fate of chemicals"},{"issue":"5","key":"ref26","doi-asserted-by":"crossref","first-page":"4317","DOI":"10.1007\/s13277-013-1566-5","article-title":"Association between cytochrome P450 2C9 gene polymorphisms and colorectal cancer susceptibility: evidence from 16 case-control studies","volume":"35","author":"H Wang","year":"2014","journal-title":"Tumour biology: the journal of the International Society for Oncodevelopmental Biology and Medicine"},{"issue":"6","key":"ref27","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1002\/ijc.28457","article-title":"Germline variation in NCF4, an innate immunity gene, is associated with an increased risk of colorectal cancer","volume":"134","author":"BM Ryan","year":"2014","journal-title":"International journal of cancer Journal international du cancer"},{"issue":"5","key":"ref28","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1158\/1055-9965.EPI-10-0675","article-title":"Genotype-Environment Interactions in Microsatellite Stable\/Microsatellite Instability-Low Colorectal Cancer: Results from a Genome-Wide Association Study","volume":"20","author":"JC Figueiredo","year":"2011","journal-title":"Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology"},{"issue":"3","key":"ref29","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"R DerSimonian","year":"1986","journal-title":"Controlled clinical trials"},{"issue":"7414","key":"ref30","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"JP Higgins","year":"2003","journal-title":"BMJ"},{"issue":"12","key":"ref31","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1093\/aje\/kws192","article-title":"Body mass index at different adult ages, weight change, and colorectal cancer risk in the National Institutes of Health-AARP Cohort","volume":"176","author":"AG Renehan","year":"2012","journal-title":"American journal of epidemiology"},{"issue":"5","key":"ref32","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/ng.133","article-title":"Genome-wide association scan identifies a colorectal cancer susceptibility locus on 11q23 and replicates risk loci at 8q24 and 18q21","volume":"40","author":"A Tenesa","year":"2008","journal-title":"Nature genetics"},{"issue":"6220","key":"ref33","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"M Uhlen","year":"2015","journal-title":"Science"},{"issue":"3","key":"ref34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1097\/00008571-199706000-00005","article-title":"The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase","volume":"7","author":"CL Crespi","year":"1997","journal-title":"Pharmacogenetics"},{"issue":"5","key":"ref35","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1016\/0006-2952(94)90493-6","article-title":"Expression of monomorphic and polymorphic N-acetyltransferases in human colon","volume":"47","author":"KF Ilett","year":"1994","journal-title":"Biochemical pharmacology"},{"issue":"19","key":"ref36","doi-asserted-by":"crossref","first-page":"6208","DOI":"10.1158\/1078-0432.CCR-09-0592","article-title":"Associations of a polymorphism in the ornithine decarboxylase gene with colorectal cancer survival","volume":"15","author":"JA Zell","year":"2009","journal-title":"Clinical cancer research: an official journal of the American Association for Cancer Research"},{"issue":"8","key":"ref37","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1097\/01.fpc.0000236339.79916.07","article-title":"UGT1A6 polymorphism and salicylic acid glucuronidation following aspirin","volume":"17","author":"Y Chen","year":"2007","journal-title":"Pharmacogenetics and genomics"},{"issue":"8","key":"ref38","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1097\/01.fpc.0000114771.78957.cb","article-title":"Human UGT1A6 pharmacogenetics: identification of a novel SNP, characterization of allele frequencies and functional analysis of recombinant allozymes in human liver tissue and in cultured cells","volume":"14","author":"S Nagar","year":"2004","journal-title":"Pharmacogenetics"},{"issue":"6","key":"ref39","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1093\/jnci\/dji066","article-title":"Genetic variants in the UGT1A6 enzyme, aspirin use, and the risk of colorectal adenoma","volume":"97","author":"AT Chan","year":"2005","journal-title":"Journal of the National Cancer Institute"},{"issue":"2","key":"ref40","doi-asserted-by":"crossref","first-page":"676","DOI":"10.3390\/cancers5020676","article-title":"Epigenetics and Colorectal Cancer Pathogenesis","volume":"5","author":"K Bardhan","year":"2013","journal-title":"Cancers"},{"issue":"2","key":"ref41","doi-asserted-by":"crossref","first-page":"e87761","DOI":"10.1371\/journal.pone.0087761","article-title":"A Gene Expression and Pre-mRNA Splicing Signature That Marks the Adenoma-Adenocarcinoma Progression in Colorectal Cancer","volume":"9","author":"M Pesson","year":"2014","journal-title":"PloS one"},{"issue":"1","key":"ref42","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1007\/s13402-011-0065-1","article-title":"Colorectal adenoma to carcinoma progression is accompanied by changes in gene expression associated with ageing, chromosomal instability, and fatty acid metabolism","volume":"35","author":"B Carvalho","year":"2012","journal-title":"Cellular Oncology (Dordrecht)"},{"issue":"5","key":"ref43","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1158\/1940-6207.CAPR-11-0106","article-title":"A randomized placebo-controlled prevention trial of aspirin and\/or resistant starch in young people with familial adenomatous polyposis","volume":"4","author":"J Burn","year":"2011","journal-title":"Cancer prevention research (Philadelphia, Pa)"},{"issue":"9809","key":"ref44","doi-asserted-by":"crossref","first-page":"2081","DOI":"10.1016\/S0140-6736(11)61049-0","article-title":"Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial","volume":"378","author":"J Burn","year":"2011","journal-title":"Lancet"},{"issue":"18","key":"ref45","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.3748\/wjg.15.2240","article-title":"No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk","volume":"15","author":"CL Thompson","year":"2009","journal-title":"World journal of gastroenterology: WJG"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0192223","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,24]],"date-time":"2018-10-24T00:41:09Z","timestamp":1540341669000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0192223"}},"subtitle":[],"editor":[{"given":"Zongli","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,2,9]]},"references-count":45,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2018,2,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0192223","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,9]]}}}