title: Role of two single nucleotide polymorphisms in secreted frizzled related protein 1 and bladder cancer risk.
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.
authors.affiliation: Institute of Pathology, University Hospital Erlangen Krankenhausstr. 8-10, 91054 Erlangen, Germany ; Early-onset Bladder Cancer Study Group.
authors.forename: Anja
authors.initials: A
authors.lastname: Rogler
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoja
authors.forename: Eileen
authors.initials: E
authors.lastname: Socher
authors.forename: Elke
authors.initials: E
authors.lastname: Nolte
authors.forename: Sven
authors.initials: S
authors.lastname: Wach
authors.forename: Wolf
authors.initials: W
authors.lastname: Wieland
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Hofstädter
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goebell
authors.forename: Bernd
authors.initials: B
authors.lastname: Wullich
authors.forename: Arndt
authors.initials: A
authors.lastname: Hartmann
authors.forename: Robert
authors.initials: R
authors.lastname: Stoehr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D035683:MicroRNAs / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics; D000099274:Frizzled-Related Proteins
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs; D011506:Proteins; D000099274:Frizzled-Related Proteins
keywords: SFRP1; SNP; Wnt signalling pathway; bladder cancer; microRNA