Open Access Research article

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

Jeanette E Eckel-Passow1, Daniel J Serie2, Brian M Bot3, Richard W Joseph4, John C Cheville5 and Alexander S Parker2*

Author Affiliations

1 Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN, USA

2 Department of Health Sciences Research, Mayo Clinic, 4500 San Pablo Road, Jacksonville, FL 32224, USA

3 Statistical Genetics, Sage Bionetworks, Seattle, WA, USA

4 Department of Hematology and Oncology, Mayo Clinic, Jacksonville, FL, USA

5 Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA

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BMC Urology 2014, 14:14  doi:10.1186/1471-2490-14-14

Published: 31 January 2014

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 (nā€‰=ā€‰23) and without (nā€‰=ā€‰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.