title: Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population-based prognostic study.
abstract: 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.
  
  
  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.affiliation: Norris Cotton Cancer Center, Geisel School of Medicine, Lebanon, NH, USA.
authors.forename: Angeline S
authors.initials: AS
authors.lastname: Andrew
authors.forename: Jiang
authors.initials: J
authors.lastname: Gui
authors.forename: Ting
authors.initials: T
authors.lastname: Hu
authors.forename: Asaf
authors.initials: A
authors.lastname: Wyszynski
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
authors.forename: Alan R
authors.initials: AR
authors.lastname: Schned
authors.forename: Sam A
authors.initials: SA
authors.lastname: Tanyos
authors.forename: Eben M
authors.initials: EM
authors.lastname: Pendleton
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Ekstrom
authors.forename: Zhongze
authors.initials: Z
authors.lastname: Li
authors.forename: Michael S
authors.initials: MS
authors.lastname: Zens
authors.forename: Mark
authors.initials: M
authors.lastname: Borsuk
authors.forename: Jason H
authors.initials: JH
authors.lastname: Moore
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Karagas
mesh_terms: D000328:Adult; D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000639:trends; D009364:Neoplasm Recurrence, Local / Q000235:genetics*; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D057285:Precision Medicine / Q000639:trends; D011379:Prognosis; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000401:mortality / Q000628:therapy*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D019010:Vascular Cell Adhesion Molecule-1; C101467:XRCC4 protein, human; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: bladder cancer; immune; polymorphism; prognosis; recurrence; survival