Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer

Chan H. Han, Yu Jing Huang, Karen H. Lu, Zhensheng Liu, Gordon Mills, Qingyi Wei, Li E. Wang

Research output: Contribution to journalArticle

12 Citations (Scopus)

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 GA 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.

Original languageEnglish (US)
Article number5
JournalJournal of Experimental and Clinical Cancer Research
Volume30
Issue number1
DOIs
StatePublished - Jan 11 2011
Externally publishedYes

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Sulfatases
Age of Onset
Ovarian Neoplasms
Alleles
Survival
Single Nucleotide Polymorphism
Genes
Heparitin Sulfate
Luciferases
Reporter Genes
Gene Frequency
Restriction Fragment Length Polymorphisms
Sample Size
Haplotypes
Sulfates
Disease-Free Survival
Intercellular Signaling Peptides and Proteins
Binding Sites
Genotype
Cell Line

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer. / Han, Chan H.; Huang, Yu Jing; Lu, Karen H.; Liu, Zhensheng; Mills, Gordon; Wei, Qingyi; Wang, Li E.

In: Journal of Experimental and Clinical Cancer Research, Vol. 30, No. 1, 5, 11.01.2011.

Research output: Contribution to journalArticle

Han, Chan H. ; Huang, Yu Jing ; Lu, Karen H. ; Liu, Zhensheng ; Mills, Gordon ; Wei, Qingyi ; Wang, Li E. / Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer. In: Journal of Experimental and Clinical Cancer Research. 2011 ; Vol. 30, No. 1.
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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 GA 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.",
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T1 - Polymorphisms in the SULF1 gene are associated with early age of onset and survival of ovarian cancer

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AU - Huang, Yu Jing

AU - Lu, Karen H.

AU - Liu, Zhensheng

AU - Mills, Gordon

AU - Wei, Qingyi

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N2 - 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 GA 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.

AB - 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 GA 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.

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