| Summary: | <p>Abstract</p> <p>Background</p> <p>SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. <it>SULF1 </it>expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of <it>SULF1 </it>would impact clinicopathologic characteristics.</p> <p>Methods</p> <p>We genotyped five common (minor allele frequency>0.05) regulatory SNPs with predicted functionalities (rs2623047 G>A, rs13264163 A>G, rs6990375 G>A, rs3802278 G>A, and rs3087714 C>T) in 168 patients with primary epithelial ovarian cancer, using the polymerase chain reaction-restriction fragment length polymorphism method.</p> <p>Results</p> <p>We found that rs2623047 G>A was significantly associated with an early age of onset of ovarian cancer in the G allele dose-response manner (<it>P </it>= 0.027; <it>P<sub>trend </sub></it>= 0.007) and that rs2623047 GG/GA genotypes were associated with longer progression-free survival; rs6990375 G>A was also associated with the early age of onset in the A allele dose-response manner (<it>P </it>= 0.013; <it>P<sub>trend</sub></it>= 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (<it>P </it>= 0.014; <it>P<sub>trend </sub></it>= 0.004). In luciferase reporter gene assays, rs2623047 G allele showed a slightly higher promoter activity than the A allele in the SKOV3 tumorigenic cell line.</p> <p>Conclusions</p> <p>These findings suggest that genetic variations in <it>SULF1 </it>may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of <it>SULF1 </it>SNPs are warranted.</p>
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