Genetic polymorphisms modify bladder cancer recurrence and survival in a USA population‐based prognostic study. (26th March 2014)

• Record Type: Journal Article
• Authors: Andrew, Angeline S.; Gui, Jiang; Hu, Ting; Wyszynski, Asaf; Marsit, Carmen J.; Kelsey, Karl T.; Schned, Alan R.; Tanyos, Sam A.; Pendleton, Eben M.; Ekstrom, Rebecca M.; Li, Zhongze; Zens, Michael S.; Borsuk, Mark; Moore, Jason H.; Karagas, Margaret R.
• Is Part Of: BJU international. Volume 115:Number 2(2015:Feb.)
• Page Start: 238
• Page End: 247
• Publication Date: 2014-03-26
• Subjects: Genitourinary organs -- Diseases -- Periodicals; Genitourinary organs -- Surgery -- Periodicals; Urology -- Periodicals; 616.6
• DOI: 10.1111/bju.12641
• Languages: English
• ISSNs: 1464-4096

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="bju12641-sec-5001" sec-type="section"> <title>Objective</title> <p>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.</p> </sec> <sec id="bju12641-sec-5002" sec-type="section"> <title>Patients and methods</title> <p>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.</p> </sec> <sec id="bju12641-sec-5003" sec-type="section"> <title>Results</title> <p>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 (<italic>P</italic> interaction < 0.001).</p> </sec> <sec id="bju12641-sec-5004" sec-type="section"> <title>Conclusions</title> <p>Our analysis suggests candidate prognostic SNPs that could guide personalised bladder cancer surveillance and treatment.</p> </sec> </abstract>