title: Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer.
abstract: BACKGROUND
  SULF1 (sulfatase 1) selectively removes the 6-O-sulphate group from heparan sulfate, changing the binding sites for extracellular growth factors. SULF1 expression has been reported to be decreased in various cancers, including ovarian cancer. We hypothesized that single nucleotide polymorphisms (SNPs) of SULF1 would impact clinicopathologic characteristics.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 (P = 0.027; Ptrend = 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 (P = 0.013; Ptrend= 0.009). The significant differences in age of disease onset persisted among carriers of haplotypes of rs2623047 and rs6990375 (P = 0.014; Ptrend = 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.
  
  
  CONCLUSIONS
  These findings suggest that genetic variations in SULF1 may play a role in ovarian cancer onset and prognosis. Further studies with large sample sizes and of the mechanistic relevance of SULF1 SNPs are warranted.
authors.affiliation: Department of Epidemiology, The University of Texas M, D, Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Chan H
authors.initials: CH
authors.lastname: Han
authors.forename: Yu-Jing
authors.initials: YJ
authors.lastname: Huang
authors.forename: Karen H
authors.initials: KH
authors.lastname: Lu
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.forename: Gordon B
authors.initials: GB
authors.lastname: Mills
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
mesh_terms: D017668:Age of Onset; D000368:Aged; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D015238:Sulfotransferases / Q000235:genetics*
chemical_list: C470791:SULF1 protein, human; D015238:Sulfotransferases