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Mp54-11 Identification and Replication of the Interplay of Four Genetic High-risk Variants for Urinary Bladder Cancer

Year: 2018

Type: article

Abstract: You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology I1 Apr 2018MP54-11 IDENTIFICATION AND REPLICATION OF THE INTERPLAY OF FOUR GENETIC HIGH-RISK VARIANTS FOR URINARY BLADDER CANCER Silvia Selinski, Meinolf Blaszkewicz, Katja Ickstadt, Holger Gerullis, Thomas Otto, Emanuel Roth, Frank Volkert, Daniel Ovsiannikov, Thomas Reckwitz, Oliver Moormann, Gergely Banfi, Peter Nyirady, Sita Vermeulen, Montserrat Garcia-Closas, Jonine Figueroa, Alison Johnson, Margaret Karagas, Manolis Kogevinas, Nuria Malats, Molly Schwenn, Debra Silverman, Stella Koutros, Nathaniel Rothman, Lambertus Kiemeney, Jan Hengstler, and Klaus Golka Silvia SelinskiSilvia Selinski More articles by this author , Meinolf BlaszkewiczMeinolf Blaszkewicz More articles by this author , Katja IckstadtKatja Ickstadt More articles by this author , Holger GerullisHolger Gerullis More articles by this author , Thomas OttoThomas Otto More articles by this author , Emanuel RothEmanuel Roth More articles by this author , Frank VolkertFrank Volkert More articles by this author , Daniel OvsiannikovDaniel Ovsiannikov More articles by this author , Thomas ReckwitzThomas Reckwitz More articles by this author , Oliver MoormannOliver Moormann More articles by this author , Gergely BanfiGergely Banfi More articles by this author , Peter NyiradyPeter Nyirady More articles by this author , Sita VermeulenSita Vermeulen More articles by this author , Montserrat Garcia-ClosasMontserrat Garcia-Closas More articles by this author , Jonine FigueroaJonine Figueroa More articles by this author , Alison JohnsonAlison Johnson More articles by this author , Margaret KaragasMargaret Karagas More articles by this author , Manolis KogevinasManolis Kogevinas More articles by this author , Nuria MalatsNuria Malats More articles by this author , Molly SchwennMolly Schwenn More articles by this author , Debra SilvermanDebra Silverman More articles by this author , Stella KoutrosStella Koutros More articles by this author , Nathaniel RothmanNathaniel Rothman More articles by this author , Lambertus KiemeneyLambertus Kiemeney More articles by this author , Jan HengstlerJan Hengstler More articles by this author , and Klaus GolkaKlaus Golka More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.1702AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genome-wide association studies identified or confirmed 15 genomic regions that modulate urinary bladder cancer risk. Little is known whether these genetic variants interact to increase bladder cancer risk. Furthermore, it is likely that different polymorphisms are relevant in smokers and non-smokers. Therefore, we conducted an interaction analysis comprising 12 susceptibility variants and totally 5049 cases and 5452 controls. METHODS 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. RESULTS 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 x 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 (OR unadjusted = 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). CONCLUSIONS In conclusion, we show that four high-risk variants can statistically interact to confer increased bladder cancer risk particularly in never smokers. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e716 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Silvia Selinski More articles by this author Meinolf Blaszkewicz More articles by this author Katja Ickstadt More articles by this author Holger Gerullis More articles by this author Thomas Otto More articles by this author Emanuel Roth More articles by this author Frank Volkert More articles by this author Daniel Ovsiannikov More articles by this author Thomas Reckwitz More articles by this author Oliver Moormann More articles by this author Gergely Banfi More articles by this author Peter Nyirady More articles by this author Sita Vermeulen More articles by this author Montserrat Garcia-Closas More articles by this author Jonine Figueroa More articles by this author Alison Johnson More articles by this author Margaret Karagas More articles by this author Manolis Kogevinas More articles by this author Nuria Malats More articles by this author Molly Schwenn More articles by this author Debra Silverman More articles by this author Stella Koutros More articles by this author Nathaniel Rothman More articles by this author Lambertus Kiemeney More articles by this author Jan Hengstler More articles by this author Klaus Golka More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Source: The Journal of Urology

DOI: 10.1016/j.juro.2018.02.1702

Language: English

Topic: Bladder and Urothelial Cancer Treatments

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: bronze

OpenAlex ID: W2758788060

FWCI:

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Cited by: 1

Related to: 10