Distribution of cigarette smoking habits according to tumor aggressiveness and tumor multiplicity at first diagnosis.

<p>Distribution of cigarette smoking habits according to tumor aggressiveness and tumor multiplicity at first diagnosis.</p

Studies that evaluated the relation between smoking intensity and tumor characteristics.

<p>Studies that evaluated the relation between smoking intensity and tumor characteristics.</p

Baseline characteristics of study population.

<p>Baseline characteristics of study population.</p

Multivariable regression analyses of smoking duration in relation to tumor aggressiveness.

<p>Multivariable regression analyses of smoking duration in relation to tumor aggressiveness.</p

Multivariable regression analyses of smoking intensity in relation to tumor aggressiveness and tumor multiplicity.

<p>Multivariable regression analyses of smoking intensity in relation to tumor aggressiveness and tumor multiplicity.</p

Association between rs9642880 (<i>MYC</i> locus) and progression-free survival in NMIBC patients.

<p>Kaplan-Meier survival plot showing association between rs9642880 genotype and progression-free survival (PFS) of non-muscle invasive bladder cancer (NMIBC) patients.</p

Prognostic Relevance of Urinary Bladder Cancer Susceptibility Loci

<div><p>In the last few years, susceptibility loci have been identified for urinary bladder cancer (UBC) through candidate-gene and genome-wide association studies. Prognostic relevance of most of these loci is yet unknown. In this study, we used data of the Nijmegen Bladder Cancer Study (NBCS) to perform a comprehensive evaluation of the prognostic relevance of all confirmed UBC susceptibility loci. Detailed clinical data concerning diagnosis, stage, treatment, and disease course of a population-based series of 1,602 UBC patients were collected retrospectively based on a medical file survey. Kaplan-Meier survival analyses and Cox proportional hazard regression were performed, and log-rank tests calculated, to evaluate the association between 12 confirmed UBC susceptibility variants and recurrence and progression in non-muscle invasive bladder cancer (NMIBC) patients. Among muscle-invasive or metastatic bladder cancer (MIBC) patients, association of these variants with overall survival was tested. Subgroup analyses by tumor aggressiveness and smoking status were performed in NMIBC patients. In the overall NMIBC group (n = 1,269), a statistically significant association between rs9642880 at 8q24 and risk of progression was observed (GT vs. TT: HR = 1.08 (95% CI: 0.76–1.54), GG vs. TT: HR = 1.81 (95% CI: 1.23–2.66), P for trend = 2.6×10⁻³). In subgroup analyses, several other variants showed suggestive, though non-significant, prognostic relevance for recurrence and progression in NMIBC and survival in MIBC. This study provides suggestive evidence that genetic loci involved in UBC etiology may influence disease prognosis. Elucidation of the causal variant(s) could further our understanding of the mechanism of disease, could point to new therapeutic targets, and might aid in improvement of prognostic tools.</p></div

Association between rs798766 (<i>TACC3/FGFR3</i> locus) and recurrence-free survival in NMIBC patients by smoking status.

<p>Kaplan-Meier survival plots showing association between rs798766 genotype and recurrence-free survival (RFS) in <b>A</b>) never cigarette smokers (Logrank P  =  3.0×10⁻⁵) and <b>B</b>) ever cigarette smokers (Logrank P  =  0.84) with non-muscle invasive bladder cancer (NMIBC).</p

Demographic and clinicopathological characteristics of included NMIBC and MIBC patients

<p>UCC: urothelial cell carcinoma; SCC: squamous cell carcinoma; AC: adenocarcinoma; p.o.: post-operative; i.v.: intravesical; CT: chemotherapy; IT: immunotherapy</p>a<p>curative intent corresponds to treatment of tumors of stage T2-T4a with N0/NX and M0/MX; palliative intent corresponds to treatment of tumors of stage T4(b) ór any T with N≥1/N+ and/or M1</p

Association of selected UBC susceptibility variants with NMIBC recurrence and progression by smoking status.

<p>CNV: copy number variant; del.  =  deletion; C.E.: converging error; HR: hazard ratio; CI: confidence interval</p>a<p>Presented effect estimates and statistical significance are based on multivariable Cox proportional hazard regression analyses with adjustment for treatment (TURT + both adjuvant i.v. CT and IT <i>vs.</i> TURT + adjuvant i.v. IT <i>vs.</i> TURT + adjuvant i.v. CT <i>vs.</i> TURT only (± one direct p.o. i.v. CT instillation));</p>b<p>rs1495741: tag SNP for <i>NAT2</i> acetylation status (GG  =  rapid, AG  =  intermediate, AA  =  slow);</p>c<p>based on exploratory analysis</p