Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort

Document Type

Journal Article

Publisher

Elsevier

Faculty

Faculty of Health, Engineering and Science

School

Health and Wellness Institute

RAS ID

18380

Comments

Okolicsanyi R.K., Faure M., Jacinto J.M.E., Chacon-Cortes D., Chambers S., Youl P.H., Haupt L.M., Griffiths L.R. (2014). Association of the SNP rs2623047 in the HSPG modification enzyme SULF1 with an Australian Caucasian Breast Cancer Cohort. Gene, 547(1), 50-54. Available here

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.

DOI

10.1016/j.gene.2014.06.009

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