Relationship of smoking status to genomic profile, chemotherapy response and clinical outcome in patients with advanced urothelial carcinoma

Monika Joshi, Monali Vasekar, Petros Grivas, Hamid Emamekhoo, Jo Ann Hsu, Vincent A. Miller, Philip J. Stephens, Siraj M. Ali, Jeffrey S. Ross, Junjia Zhu, Joshua Warrick, Joseph J. Drabick, Sheldon L. Holder, Matthew Kaag, Min Li, Sumanta Kumar Pal

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Smoking has been linked to urothelial carcinoma (UC), but the implications on genomic profile and therapeutic response are poorly understood. To determine how smoking history impacts genomic profile and chemotherapy response, clinicopathologic data was collected for patients with metastatic UC (mUC) across 3 academic medical centers and comprehensive genomic profiling (CGP) was performed through a CLIA-certified lab. Unsupervised hierarchical clustering based on smoking status was used to categorize the frequency of genomic alterations (GAs) amongst current smokers (CS), ex-smokers (ES) and non-smokers (NS), and survival was compared in these subsets. Fisher's exact test identified significant associations between GAs and smoking status. Amongst 83 patients, 23%, 55% and 22% were CS, ES, and NS, respectively, and 95% of patients had stage IV disease. With a median follow up of 14.4 months, the median overall survival (OS) was significantly higher in NS and ES (combined) as compared to CS (51.6 vs 15.6 months; P = 0.04). Of 315 cancer-related genes and 31 genes often related to rearrangement tested, heatmaps show some variations amongst the subsets. GAs in NSD1 were more frequent in CS as compared to other groups (P < 0.001). CS status negatively impacts OS in patients with mUC and is associated with genomic alterations that could have therapeutic implications.

Original languageEnglish (US)
Pages (from-to)52442-52449
Number of pages8
JournalOncotarget
Volume7
Issue number32
DOIs
StatePublished - Aug 1 2016

All Science Journal Classification (ASJC) codes

  • Oncology

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