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Int J Clin Exp Pathol 2013;6(10):1984-1998

Original Article
Role of two single nucleotide polymorphisms in secreted frizzled re-lated protein 1 and
bladder cancer risk

Anja Rogler, Sabine Hoja, Eileen Socher, Elke Nolte, Sven Wach, Wolf Wieland, Ferdinand Hofstädter, Peter J Goebell, Bernd Wullich, Arndt
Hartmann, Robert Stoehr

Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054 Erlangen, Germany; Department of Urology, University
Hospital Erlangen, Krankenhausstr. 12, 91054 Erlangen, Germany; Caritas St. Josef Medical Center, Department of Urology, University of
Regensburg, Landshuter Straße 65, 93053 Regensburg, Germany; Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee
11, 93053 Regensburg, Germany; Early-onset Bladder Cancer Study Group

Received August 14, 2013; Accepted September 3, 2013; Epub September 15, 2013; Published October 1, 2013

Abstract: In this study, we determined the genotype distribution of two single nucleotide polymorphisms (SNPs) in secreted frizzled related
protein 1 (SFRP1), rs3242 and rs921142, in a Caucasian bladder cancer case-control study. Allelic variants of the SNPs were determined
using restriction fragment length polymorphism (RFLP) analysis and partly verified by sequencing analysis. Overall, DNA from 188 consecutive
and 215 early-onset bladder cancer patients (≤45 years) as well as from 332 controls was investigated. Potential microRNA binding sites were
determined for rs3242, and microRNA expression was analysed in cell lines and tumour specimens. We observed a remarkable distribution
difference in rs3242 between bladder cancer patients and healthy controls (p=0.05). Additionally, we found a significant difference in genotype
distribution (p=0.032), resulting from the difference of early-onset patients and the control group (p=0.007). The risk allele T showed increased
frequency in the early-onset patient group (p=0.002). Genotype-dependent differences of microRNA binding capacity were predicted in SFRP1
mRNA for two microRNAs. Hsa-miR-3646 showed strong expression in cell lines and tumour tissue, whereas hsa-miR-603 exhibited weak
expression. The rs921142 SNP showed no significant association with bladder cancer risk. This is the first study to describe an association of
the SFRP1 SNP rs3242 and bladder cancer risk as well as the influence of rs3242 on genotype-dependent microRNA capacity on SFRP1
mRNA. The onset of bladder seems to be associated with the increased occurrence of the T-allele in rs3242. (IJCEP1308034).

Keywords: SFRP1, SNP, bladder cancer, microRNA, Wnt signalling pathway

Address correspondence to: Dr. Robert Stöhr, Institute of Pathology, University Hospital Erlangen, Krankenhausstr. 8-10, 91054 Erlangen,
Germany. Tel: +49 (0)9131 85 43610; Fax +49 (0)9131 85 25785; E-mail: Robert.stoehr@uk-erlangen.de