Bladder cancer is the fourth most common malignancy in U.S. men. Current treatments for non-invasive bladder tumors often appear initially effective, yet the rates of recurrent disease are high. Clinically useful predictors of the recurrent bladder cancer phenotype have not yet been identified. Major biological processes involved in bladder carcinogenesis include apoptosis, cell cycle, DNA repair, immune surveillance, and xenobiotic metabolism. We hypothesized that genetic variation in genes involved in each of these pathways may modify bladder cancer susceptibility and prognosis. Methods: To examine the independent and interacting effects, we analyzed variant genotypes hypothesized to modify these processes in 818 transitional cell carcinoma cases and 1167 controls enrolled in a case – control study of incident bladder cancer conducted in New Hampshire, U.S.A. Cases were followed over time to ascertain recurrence and survival status. We evaluated gene–gene interactions using Multifactor Dimensionality Reduction (MDR). Results: In the metabolism pathway, the variant form of the metabolism gene HSD3B2 was associated with increased risk (adjusted OR 1.85 95%CI 1.31–2.62) and ALDH2 variants had shorter time to first bladder cancer recurrence (adjusted HR non-invasive 1.94 95%CI 1.32–2.84). We observed longer survival among bladder cancer cases with non-invasive tumors associated with DNA repair XRCC4 heterozygous genotype compared with wildtype (adjusted HR 0.53 95%CI 0.38–0.74) and for invasive cases for immune pathway GATA3 heterozygotes (adjusted HR 0.11 95%CI 0.03–0.39). Conclusions: Our analysis suggests candidate SNPs for further clinical evaluation as prognostic markers and may lead to more personalized bladder cancer surveillance guidelines.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):A66.