Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer

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• dc.contributor.author Selinski, Silviaca
• dc.contributor.author Kogevinas, Manolisca
• dc.contributor.author Golka, Klausca
• dc.date.accessioned 2018-05-03T07:18:25Z
• dc.date.available 2018-05-03T07:18:25Z
• dc.date.issued 2017
• dc.description.abstract Little is known whether genetic variants identified in genome-wide association studies interact to increase bladder cancer risk. Recently, we identified two- and three-variant combinations associated with a particular increase of bladder cancer risk in a urinary bladder cancer case-control series (Leibniz Research Centre for Working Environment and Human Factors at TU Dortmund (IfADo), 1501 cases, 1565 controls). In an independent case-control series (Nijmegen Bladder Cancer Study, NBCS, 1468 cases, 1720 controls) we confirmed these two- and three-variant combinations. Pooled analysis of the two studies as discovery group (IfADo-NBCS) resulted in sufficient statistical power to test up to four-variant combinations by a logistic regression approach. The New England and Spanish Bladder Cancer Studies (2080 cases and 2167 controls) were used as a replication series. Twelve previously identified risk variants were considered. The strongest four-variant combination was obtained in never smokers. The combination of rs1014971[AA] near apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3A (APOBEC3A) and chromobox homolog 6 (CBX6), solute carrier family 1s4 (urea transporter), member 1 (Kidd blood group) (SLC14A1) exon single nucleotide polymorphism (SNP) rs1058396[AG, GG], UDP glucuronosyltransferase 1 family, polypeptide A complex locus (UGT1A) intron SNP rs11892031[AA] and rs8102137[CC, CT] near cyclin E1 (CCNE1) resulted in an unadjusted odds ratio (OR) of 2.59 (95% CI = 1.93-3.47; P = 1.87 × 10-10), while the individual variant ORs ranged only between 1.11 and 1.30. The combination replicated in the New England and Spanish Bladder Cancer Studies (ORunadjusted = 1.60, 95% CI = 1.10-2.33; P = 0.013). The four-variant combination is relatively frequent, with 25% in never smoking cases and 11% in never smoking controls (total study group: 19% cases, 14% controls). In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers.
• dc.format.mimetype application/pdf
• dc.identifier.citation Selinski S, Blaszkewicz M, Ickstadt K, Gerullis H, Otto T, Roth E. et al. Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancer. Carcinogenesis. 2017 Dec 7;38(12):1167-79. DOI: 10.1093/carcin/bgx102
• dc.identifier.doi http://dx.doi.org/10.1093/carcin/bgx102
• dc.identifier.issn 0143-3334
• dc.identifier.uri http://hdl.handle.net/10230/34527
• dc.language.iso eng
• dc.publisher Oxford University Pressca
• dc.relation.ispartof Carcinogenesis. 2017 Dec 7;38(12):1167-79
• dc.rights Copyright © The Author 2017. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.other Bufeta -- Càncer
• dc.subject.other Càncer -- Aspectes genètics
• dc.title Identification and replication of the interplay of four genetic high-risk variants for urinary bladder cancerca
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion