OBJECTIVE: To identify genetic variants that modify bladder cancer prognosis focusing on genes involved in major biological carcinogenesis processes (apoptosis, proliferation, DNA repair, hormone regulation, immune surveillance, and cellular metabolism), as nearly half of patients with bladder cancer experience recurrences reliable predictors of this recurrent phenotype are needed to guide surveillance and treatment. PATIENTS AND METHODS: We analysed variant genotypes hypothesised to modify these processes in 563 patients with urothelial-cell carcinoma enrolled in a population-based study of incident bladder cancer conducted in New Hampshire, USA. After diagnosis, patients were followed over time to ascertain recurrence and survival status, making this one of the first population-based studies with detailed prognosis data. Cox proportional hazards regression was used to assess the relationship between single nucleotide polymorphisms (SNPs) and prognosis endpoints. RESULTS: Patients with aldehyde dehydrogenase 2 (ALDH2) variants had a shorter time to first recurrence (adjusted non-invasive hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.29-2.78). There was longer survival among patients with non-invasive tumours associated with DNA repair X-ray repair cross-complementing protein 4 (XRCC4) heterozygous genotype compared with wild-type (adjusted HR 0.53, 95% CI 0.38-0.74). Time to recurrence was shorter for patients who had a variant allele in vascular cellular adhesion molecule 1 (VCAM1) and were treated with immunotherapy (P interaction < 0.001). CONCLUSIONS: Our analysis suggests candidate prognostic SNPs that could guide personalised bladder cancer surveillance and treatment.
OBJECTIVE: To identify genetic variants that modify bladder cancer prognosis focusing on genes involved in major biological carcinogenesis processes (apoptosis, proliferation, DNA repair, hormone regulation, immune surveillance, and cellular metabolism), as nearly half of patients with bladder cancer experience recurrences reliable predictors of this recurrent phenotype are needed to guide surveillance and treatment. PATIENTS AND METHODS: We analysed variant genotypes hypothesised to modify these processes in 563 patients with urothelial-cell carcinoma enrolled in a population-based study of incident bladder cancer conducted in New Hampshire, USA. After diagnosis, patients were followed over time to ascertain recurrence and survival status, making this one of the first population-based studies with detailed prognosis data. Cox proportional hazards regression was used to assess the relationship between single nucleotide polymorphisms (SNPs) and prognosis endpoints. RESULTS:Patients with aldehyde dehydrogenase 2 (ALDH2) variants had a shorter time to first recurrence (adjusted non-invasive hazard ratio [HR] 1.90, 95% confidence interval [CI] 1.29-2.78). There was longer survival among patients with non-invasive tumours associated with DNA repair X-ray repair cross-complementing protein 4 (XRCC4) heterozygous genotype compared with wild-type (adjusted HR 0.53, 95% CI 0.38-0.74). Time to recurrence was shorter for patients who had a variant allele in vascular cellular adhesion molecule 1 (VCAM1) and were treated with immunotherapy (P interaction < 0.001). CONCLUSIONS: Our analysis suggests candidate prognostic SNPs that could guide personalised bladder cancer surveillance and treatment.
Authors: Sharon R Pine; Leah E Mechanic; Stefan Ambs; Elise D Bowman; Stephen J Chanock; Christopher Loffredo; Peter G Shields; Curtis C Harris Journal: J Natl Cancer Inst Date: 2007-09-11 Impact factor: 13.506
Authors: Marcia R Saban; Michael A O'Donnell; Robert E Hurst; Xue-Ru Wu; Cindy Simpson; Igor Dozmorov; Carole Davis; Ricardo Saban Journal: BMC Immunol Date: 2008-02-11 Impact factor: 3.615
Authors: Michael J Kerins; Pengfei Liu; Wang Tian; William Mannheim; Donna D Zhang; Aikseng Ooi Journal: Mol Cell Biol Date: 2019-06-13 Impact factor: 4.272
Authors: Nadezda Lipunova; Anke Wesselius; Kar K Cheng; Frederik J van Schooten; Jean-Baptiste Cazier; Richard T Bryan; Maurice P Zeegers Journal: Biomark Cancer Date: 2019-12-30