Show simple item record Selinski S Blaszkewicz M Ickstadt K Gerullis H Otto T Roth E Volkert F Ovsiannikov D Moormann O Bánfi, Gergely Nyirády, Péter Vermeulen SH Garcia-Closas M Figueroa JD Johnson A Karagas MR Kogevinas M Malats N Schwenn M Silverman DT Koutros S Rothman N Kiemeney LA Hengstler JG Golka K 2018-06-04T07:25:22Z 2018-06-04T07:25:22Z 2017
dc.identifier.citation pagination=1167-1179; journalVolume=38; journalIssueNumber=12; journalTitle=CARCINOGENESIS;
dc.identifier.uri doi:10.1093/carcin/bgx102
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 (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 APOBEC3A and CBX6, SLC14A1 exon SNP rs1058396[AG,GG], UGT1A intron SNP rs11892031[AA], and rs8102137[CC,CT] near CCNE resulted in an unadjusted odds ratio of 2.59 (95% CI = 1.93-3.47; P = 1.87x10-10), while the individual variant odds ratios ranged only between 1.11-1.30. 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.relation.ispartof urn:issn:0143-3334
dc.title Identification and replication of the interplay of four genetic high risk variants for urinary bladder cancer
dc.type Journal Article 2018-01-02T11:32:30Z
dc.language.rfc3066 en
dc.identifier.mtmt 3279713
dc.identifier.pubmed 29028944
dc.contributor.department SE/AOK/K/Urológiai Klinika
dc.contributor.institution Semmelweis Egyetem

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