MP68-16 ASSOCIATION OF GENETIC VARIANTS WITH THE OCCURRENCE OF BLADDER CANCER IN AN ARSENIC-EXPOSED POPULATION

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research IV1 Apr 2015MP68-16 ASSOCIATION OF GENETIC VARIANTS WITH THE OCCURRENCE OF BLADDER CANCER IN AN ARSENIC-EXPOSED POPULATION Mario I. Fernandez, Cecilia Vial, Patricio Valdebenito, Eduardo Chaparro, Karena Espinoza, and Gabriela Repetto Mario I. FernandezMario I. Fernandez More articles by this author , Cecilia VialCecilia Vial More articles by this author , Patricio ValdebenitoPatricio Valdebenito More articles by this author , Eduardo ChaparroEduardo Chaparro More articles by this author , Karena EspinozaKarena Espinoza More articles by this author , and Gabriela RepettoGabriela Repetto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.2478AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inhabitants of Antofagasta (Northern Chile) were exposed to significantly elevated arsenic in drinking water between 1958 and 1971. As a consequence, incidence of bladder cancer (BC) in this city is currently 4 to 5 times higher than in the rest of the country (24.8 vs. 6/100,000). Carcinogenesis of arsenic-related BC is poorly understood to date. Therefore, we aimed to perform a genome-wide association study on individuals exposed to arsenic, looking for genetic variants associated to BC susceptibility among cases and controls. METHODS Subjects were invited to participate after signing an informed consent. Epidemiologic and clinical data (demographics, smoking history, family history of cancer and medical history) were collected during an in-person interview using a validated questionnaire and a blood sample was obtained. Patient variables were assessed by means of the Pearson χ2 test, comparing cases with controls. Differences in continuous variables were evaluated by the Student's t test. DNA samples were analyzed using Affymetrix Genome-Wide SNP Array 6.0. After filtering by missingness per individual, missingness per marker allele frequency and Hardy Weinberg Equilibrium we obtained 788,705 SNPs to be analyzed. RESULTS Males were predominant among cases and controls. Meanwhile, there were no significant differences in terms of mean age, familial history of BC, occupational exposure data or smoking status between groups. Tobacco smoking prevalence according to WHO classification was significantly frequent among cases and controls (59.5 and 58.3% respectively; p=0.55). The study population was found to be homogeneous after performance of principal component analysis for stratification, clustering the different individuals with the identity by state. Two regions with a significant association were identified after association tests comparing cases and controls: (a) rs4838646 in chromosome 10 (p=3.8E-06; OR 0.14) and (b) rs12371702 in chromosome 12 (p=5.8E-06; OR 7.2). Previous studies have linked polymorphisms in the former region to BC susceptibility. CONCLUSIONS Initial results of a BC genomic case-control study in an arsenic-exposed population are presented and raise candidate risk SNPs that need to be further validated in independent analyses. Additional insights into the genetics and biology of arsenic-related BC are also provided. However, further analysis is warranted after completion of recruitment. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e863-e864 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mario I. Fernandez More articles by this author Cecilia Vial More articles by this author Patricio Valdebenito More articles by this author Eduardo Chaparro More articles by this author Karena Espinoza More articles by this author Gabriela Repetto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...