title: Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian breast cancer cohort.
abstract: Breast cancer is the second most common cancer worldwide and the most common cancer reported in women. This malignant tumour is characterised by a number of specific features including uncontrolled cell proliferation. It ranks fifth in the world as a cause of cancer death overall in developed countries and is the second most frequent cause of cancer death in women. Early diagnosis increases 5-year survival rates up to 95%. Heparan sulfate proteoglycans (HSPGs) are complex proteins composed of a core protein to which a number of highly sulfated side chains attach, ubiquitous to the cell surface and within the extracellular matrix. HSPG side chains are synthesised by a highly co-ordinated process resulting in distinct sulfation patterns, which determine specific interactions with cell-signalling partners including growth factors, their receptors, ligands and morphogens. The enzymes responsible for chain initiation, elongation and sulfation are critical for creating HS chain variability conferring biological functionality. This study investigated a single nucleotide polymorphism in SULF1, the enzyme responsible for the 6-O desulfation of heparan sulfate side chains. We investigated this SNP in an Australian Caucasian case-control breast cancer population and found a significant association between SULF1 and breast cancer at both the allelic and genotypic levels (allele, p=0.016; genotype, p=0.032). Our results suggest that the rs2623047 SNP in SULF1 may impact breast cancer susceptibility. Specifically, the T allele of rs2623047 in SULF1 is associated with an increased risk of developing breast cancer in our cohort. The identification of markers including SULF1 may improve detection of this disease at its earliest stages improving patient treatment and prognosis.
authors.affiliation: Genomics Research Centre, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Rachel K
authors.initials: RK
authors.lastname: Okolicsanyi
authors.affiliation: Genomics Research Centre, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia; AgroSup Dijon, 26 Boulevard Docteur Petitjean, 21000 Dijon, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Faure
authors.affiliation: Griffith Health Institute, Griffith University, Southport, QLD, Australia.
authors.forename: Jose M E
authors.initials: JM
authors.lastname: Jacinto
authors.affiliation: Genomics Research Centre, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Diego
authors.initials: D
authors.lastname: Chacon-Cortes
authors.affiliation: Griffith Health Institute, Griffith University, Southport, QLD, Australia; Cancer Council Queensland, Australia; Health and Wellness Institute, Edith Cowan University, Australia; Centre for Clinical Research, University of Queensland, Australia.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Chambers
authors.affiliation: Griffith Health Institute, Griffith University, Southport, QLD, Australia; Cancer Council Queensland, Australia; School of Public Health, Queensland University of Technology, Australia.
authors.forename: Philippa H
authors.initials: PH
authors.lastname: Youl
authors.affiliation: Genomics Research Centre, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Larisa M
authors.initials: LM
authors.lastname: Haupt
authors.affiliation: Genomics Research Centre, Institute for Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia. Electronic address: lyn.griffiths@qut.edu.au.
authors.forename: Lyn R
authors.initials: LR
authors.lastname: Griffiths
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D004587:Electrophoresis, Agar Gel; D005260:Female; D055106:Genome-Wide Association Study; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D015238:Sulfotransferases / Q000235:genetics*; D015996:Survival Rate; D044465:White People
chemical_list: D014408:Biomarkers, Tumor; D019812:Heparan Sulfate Proteoglycans; C470791:SULF1 protein, human; D015238:Sulfotransferases
keywords: Breast cancer; HSPG; PCR-RFLP; SNP rs2623047; SULF-1