title: Application of multi-SNP approaches Bayesian LASSO and AUC-RF to detect main effects of inflammatory-gene variants associated with bladder cancer risk.
abstract: The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Evangelina López
authors.initials: EL
authors.lastname: de Maturana
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Yuanqing
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Systems Biology Department, University of Vic, Vic, Spain.
authors.forename: M Luz
authors.initials: ML
authors.lastname: Calle
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Systems Biology Department, University of Vic, Vic, Spain.
authors.forename: Víctor
authors.initials: V
authors.lastname: Urrea
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain ; Institut Municipal d'Investigació Mèdica - Hospital del Mar, Barcelona, Spain.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain ; Systems Biology Department, University of Vic, Vic, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Petrus
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.affiliation: Universidad de Oviedo, Oviedo, Spain.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Montserrat
authors.initials: M
authors.lastname: García-Closas
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Anna
authors.initials: A
authors.lastname: González-Neira
authors.affiliation: Institut Municipal d'Investigació Mèdica - Hospital del Mar, Barcelona, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Vellalta
authors.affiliation: Hospital Universitario de Elche, Elche, Spain ; Hospital Universitario Ramon y Cajal, Madrid, Spain.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Carrato
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain ; Institut de Biologia Evolutiva (UPF-CSIC), Barcelona, Spain ; Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain ; Instituto Nacional de Bioinformática, Barcelona, Spain.
authors.forename: Arcadi
authors.initials: A
authors.lastname: Navarro
authors.affiliation: Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain ; Institut de Biologia Evolutiva (UPF-CSIC), Barcelona, Spain ; Instituto Nacional de Bioinformática, Barcelona, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Lorente-Galdós
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, Bethesda, Maryland, United States of America.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain ; Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
authors.forename: Francisco X
authors.initials: FX
authors.lastname: Real
authors.affiliation: Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
authors.affiliation: Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), Madrid, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Malats
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001185:Artificial Intelligence; D001499:Bayes Theorem; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D018836:Inflammation Mediators / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*; D013781:Texas; D001749:Urinary Bladder Neoplasms / Q000209:etiology*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D018836:Inflammation Mediators