ANKS1B is a smoking-related molecular alteration in clear cell renal cell carcinoma

Jeanette E. Eckel-Passow, Daniel J. Serie, Brian M. Bot, Richard W. Joseph, John C. Cheville, Alexander S. Parker

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Background: An association between cigarette smoking and increased risk of clear cell renal cell carcinoma (ccRCC) has been established; however, there are limited data regarding the molecular mechanisms that underlie this association. We used a multi-stage design to identify and validate genes that are associated with smoking-related ccRCC. Methods. We first conducted a microarray study to compare gene expression patterns in patient-matched ccRCC and normal kidney tissues between patients with (n = 23) and without (n = 42) a history of smoking. Analyses were first stratified on obesity status (the other primary risk factor for ccRCC) and then combined and analyzed together. To identify genes where the fold change in smokers relative to non-smokers was different in tumor tissues in comparison to patient-matched normal kidney tissues, we identified Affymetrix probesets that had a significant tissue type-by-smoking status interaction pvalue. We then performed RT-PCR validation on the top eight candidate genes in an independent sample of 28 smokers and 54 non-smokers. Results: We identified 15 probesets that mapped to eight genes that had candidate associations with smoking-related ccRCC: ANKS1B, ACOT6, PPWD1, EYS, LIMCH1, CHRNA6, MT1G, and ZNF600. Using RT-PCR, we validated that expression of ANKS1B is preferentially down-regulated in smoking-related ccRCC. Conclusion: We provide the first evidence that ANKS1B expression is down regulated in ccRCC tumors relative to patient-matched normal kidney tissue in smokers. Thus, ANKS1B should be explored further as a novel avenue for early detection as well as prevention of ccRCC in smokers.

Original languageEnglish (US)
Article number14
JournalBMC Urology
Volume14
Issue number1
DOIs
StatePublished - Jan 31 2014

ASJC Scopus subject areas

  • Reproductive Medicine
  • Urology

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