Systematic Review: Genetic Associations for Prognostic Factors of Urinary Bladder Cancer

Abstract

Introduction:Many germline associations have been reported for urinary bladder cancer (UBC) outcomes and prognostic characteristics. It is unclear whether there are overlapping genetic patterns for various prognostic endpoints. We aimed to review contemporary literature on genetic associations with UBC prognostic outcomes and to identify potential overlap in reported genes.Methods:EMBASE, MEDLINE, and PubMed databases were queried for relevant articles in English language without date restrictions. The initial search identified 1346 articles. After exclusions, 112 studies have been summarized. Cumulatively, 316 single-nucleotide polymorphisms (SNPs) were reported across prognostic outcomes (recurrence, progression, death) and characteristics (tumor stage, grade, size, age, risk group). There were considerable differences between studied outcomes in the context of genetic associations. The most commonly reported SNPs were located in OGG1, TP53, and MDM2. For outcomes with the highest number of reported associations (ie, recurrence and death), functional enrichment annotation yields different terms, potentially indicating separate biological mechanisms.Conclusions:Our study suggests that all UBC prognostic outcomes may have different biological origins with limited overlap. Further validation of these observations is essential to target a phenotype that could best predict patient outcome and advance current management practices.

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

“…Based on these evaluations, the European Organization for Research and Treatment of Cancer (EORTC) risk tables allow stratifying patients into low-, intermediate-and high-risk for reoccurrence or progression [17]. However, this may not be appropriate given that they are defined by different prognostic factors and require different follow-up strategies [27]. Prior disease reoccurrence rate and the number of distinct tumors are the strongest predictors of BLCa reoccurrence, whereas the most significant prognostic factors for disease progression and disease-specific survival are tumor stage and grade, and presence of CIS [17].…”

Genome-wide Meta-analysis Identifies Novel Genes Associated with Recurrence and Progression in Non–muscle-invasive Bladder Cancer

“…Unfortunately, the validity of these associations is unknown, as most findings were not replicated in independent series [6]. Indeed, in a previous replication study from our group, we were able to replicate only six out of 114 previously reported associations for UBC prognosis and treatment response [7].…”

“…We checked the associations of SNPs that were previously published for association with RFS or PFS in the whole NMIBC group, as summarized by Lipunova et al [6] plus rs4976845 (published for association with progression after the review [16]).…”

“…For example, in 2010, Chen et al [5] reported a replicated association between germline genetic variations in the sonic hedgehog pathway and clinical outcomes in NMIBC. A recent review by Lipunova et al [6] provides an overview of the currently published germline genetic associations for NMIBC and MIBC outcomes, also for specific subgroups such as bacillus Calmette-Guérin (BCG)-treated patients. A total of 81 associations for recurrence and 24 for progression were reported, based on a final set of 112 articles.…”

Immunological Estimation of Inflammatory Interleukins (IL-4, IL-6 & IL-10) Among Patients with Bladder Cancer

“…Table (17) observe that the mean level of concentrations for IL-4 (pg\ml), IL-6 (pg\ml) and IL-10 (pg\ml) were positive correlated with levels of Ages (years) as indicated by the score of (.014, 0.095, 0.041) respectively, statistically this correlation was nonsignificant (P-value=0.9, 0.4,0.7) respectively. Interleukin 4, a Th2-lymphocyte-derived immunoregulatory cytokine produced by activated CD4+ T cell, mast cell, basophils and eosinophil, IL-4 is the central differentiation factor driving Th2 development, inhibiting Th1 differentiation and eliminating extracellular pathogens.…”