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dc.contributor.authorGibbs, David Corley
dc.contributor.authorSong, Mingyang
dc.contributor.authorMcCullough, Marjorie L.
dc.contributor.authorUm, Caroline Y.
dc.contributor.authorBostick, Roberd M.
dc.contributor.authorWu, Kana
dc.contributor.authorFlanders, W. Dana
dc.contributor.authorGiovannucci, Edward
dc.contributor.authorJenab, Mazda
dc.contributor.authorBrustad, Magritt
dc.contributor.authorTjønneland, Anne
dc.contributor.authorPerez-Cornago, Aurora
dc.contributor.authorTrichopoulou, Antonia
dc.contributor.authorTsilidis, Konstantinos K.
dc.contributor.authorHultdin, Johan
dc.contributor.authorGurrea, Aurelio Barricarte
dc.contributor.authorBueno-De-Mesquita, Bas
dc.contributor.authorMahamat-Saleh, Yahya
dc.contributor.authorKühn, Tilman
dc.contributor.authorGunter, Marc
dc.contributor.authorWeiderpass, Elisabete
dc.contributor.authorFedirko, Veronika
dc.date.accessioned2021-04-08T12:45:50Z
dc.date.available2021-04-08T12:45:50Z
dc.date.issued2019-10-15
dc.description.abstract<i>Background</i> - Higher circulating 25-hydroxyvitamin-D [25(OH)D] concentrations are consistently inversely associated with colorectal cancer (CRC) risk in observational studies. However, it is unknown whether this association depends on the functional GC-rs4588*A (Thr436Lys) variant encoding the vitamin D–binding protein-2 (DBP2) isoform, which may affect vitamin D status and bioavailability.<p> <p><i>Methods</i> - We analyzed data from 1710 incident CRC cases and 1649 incidence-density–matched controls nested within three prospective cohorts of mostly Caucasians. Study-specific incidence rate ratios (RRs) for associations of prediagnostic, season-standardized 25(OH)D concentrations according to DBP2 isoform with CRC were estimated using multivariable unconditional logistic regression and were pooled using fixed-effects models. All statistical significance tests were two-sided.<p> <p><i>Results</i> - The odds of having 25(OH)D concentrations less than 50 nmol/L (considered insufficient by the Institute of Medicine) were 43% higher for each DBP2-encoding variant (rs4588*A) inherited (per DBP2 odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.27 to 1.62, P<sub>trend</sub> = 1.2 × 10−8). The association of 25(OH)D concentrations with CRC risk differed by DBP2: 25(OH)D concentrations considered sufficient (≥ 50 nmol/L), relative to deficient (< 30 nmol/L), were associated with a 53% lower CRC risk among individuals with the DBP2 isoform (RR = 0.47, 95% CI = 0.33 to 0.67), but with a non–statistically significant 12% lower risk among individuals without it (RR = 0.88, 95% CI = 0.61 to 1.27) (P<sub>heterogeneity</sub> = .01). Conclusions Our results suggest that the 25(OH)D-CRC association may differ by DBP isoform, and those with a DBP2-encoding genotype linked to vitamin D insufficiency may particularly benefit from adequate 25(OH)D for CRC prevention.en_US
dc.identifier.citationGibbs, Song, McCullough, Um, Bostick, Wu, Flanders, Giovannucci, Jenab, Brustad, Tjønneland, Perez-Cornago, Trichopoulou, Tsilidis, Hultdin, Gurrea, Bueno-De-Mesquita, Mahamat-Saleh, Kühn, Gunter, Weiderpass, Fedirko. Association of circulating Vitamin D with colorectal cancer depends on Vitamin D-binding protein isoforms: A pooled, nested, case-control study. JNCI Cancer Spectrum. 2020;4:pkz083(1):1-8en_US
dc.identifier.cristinIDFRIDAID 1899669
dc.identifier.doi10.1093/jncics/pkz083
dc.identifier.issn2515-5091
dc.identifier.urihttps://hdl.handle.net/10037/20822
dc.language.isoengen_US
dc.publisherOxford University Pressen_US
dc.relation.journalJNCI Cancer Spectrum
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/DG-SANCO/?/?/?/?/en_US
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Health sciences: 800::Community medicine, Social medicine: 801en_US
dc.subjectVDP::Medisinske Fag: 700::Helsefag: 800::Samfunnsmedisin, sosialmedisin: 801en_US
dc.titleAssociation of circulating Vitamin D with colorectal cancer depends on Vitamin D-binding protein isoforms: A pooled, nested, case-control studyen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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