Germline prognostic markers for urinary bladder cancer: Obstacles and opportunities

Abstract

Urinary bladder cancer is a heterogeneous disease with diverse genetic and environmental risk factors that can influence disease risk or clinical course for recurrence, progression, and survival. Therefore, identification of these factors is paramount for disease prevention and optimal clinical management of bladder cancer patients. Of particular interest is the need to identify molecular biomarkers that can give accurate assessment of tumor biological potential and to predict treatment response. Recent advances in molecular biology, cytogenetic and genomic research have spurred discovery efforts for novel genetic, epigenetic, and proteomic biomarkers that are prognostic for cancer. This review focuses on some of the important germline polymorphisms found to be correlated with clinical outcomes in bladder cancer. So far the majority of the identified candidate loci was based on prior knowledge of pathogenesis and had not been validated for clinical applications. The future challenges are to analyze the wealth of information from whole-genome studies, to understand the underlying biological mechanisms of these associations, the network of gene-gene and gene-environment interactions, and to apply these markers for the identification of high-risk population for targeted, personalized therapy.

Clinical significance of protocadherin-8 (PCDH8) promoter methylation in bladder cancer

“…2 Prognostic biomarkers are vital for the accurate prediction of outcome and to determine which patients need more aggressive postoperative intervention. [25][26][27] PCDH8 methylation was present in a high proportion of bladder cancer tissues in the present study, and was associated with malignant behaviour. PCDH8 promoter methylation may therefore represent a useful prognostic biomarker in bladder cancer.…”

Genetic score of multiple risk‐associated single nucleotide polymorphisms is a marker for genetic susceptibility to bladder cancer

“…In the past, many inherited genetic variants were reported to be associated with bladder cancer risk using a candidate‐gene approach. However, few of these candidate‐gene associations has been consistently replicated (Chang et al, ). In , Kiemeney et al conducted the first genome‐wide association study (GWAS) of urinary bladder cancer in a European population and identified two single‐nucleotide polymorphisms (SNPs) that were significantly associated with bladder cancer risk (Kiemeney et al, ).…”

Urinary Bladder Cancer Susceptibility Markers. What Do We Know about Functional Mechanisms?

“…This suggests the contribution of genetic variation in determining bladder cancer risk [18]. In recent years, GWAS have emerged as a powerful approach in the discovery of genetics underlying complex traits like cancer.…”