Association of heparan sulfate proteoglycans SDC1 and SDC4 polymorphisms with breast cancer in an Australian Caucasian population
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Breast cancer is a common disease in both developing and developed countries with early identification and treatment improving prognosis and survival. Heparan sulfate proteoglycans (HSPGs) are key components of the extracellular matrix (ECM) that mediate cell adhesion, motility, proliferation, invasion and cell signalling. Members of the syndecan family of HSPGs have been identified to be involved in breast cancer progression through their varied interactions with a number of growth factors, ligands and receptors. Specifically, high expression levels of syndecan-1 (SDC1) have been demonstrated in more invasive breast tumours while elevated syndecan-4 (SDC4) levels have been identified to correspond with improved prognosis. With genetic changes in the syndecans and their association with breast cancers plausible, we examined two single nucleotide polymorphisms in SDC1 (rs1131351) and SDC4 (rs67068737) within an Australian Caucasian breast cancer case/control population. No association was found with SDC4 and breast cancer in our population. However, a significant association between SDC1 and breast cancer was identified in both our case/control population and in a replication cohort. When both populations were combined for analysis, this association became more significant (genotype, p = 0.0003; allele, p = 0.0001). This data suggests an increased risk of developing breast cancer associated with the presence of the C allele of the SDC1 rs1131351 single nucleotide polymorphism (SNP) and may provide a marker toward early breast cancer detection.
KeywordsHSPG Syndecan Breast cancer SNP
RKO is supported by an Australian Postgraduate Award stipend, and the authors wish to acknowledge the support of the Estate of the late Clem Jones AO, Cancer Council Queensland, Cancer Australia Grant (100639) and the Griffith Health Institute, Griffith University. SKC is an Australian Research Council Future Fellow. PHY is an NHMRC Early Career Fellow.
Conflicts of interest
- 1.ABS. Leading causes of death by gender. In: 3303.0 Causes of Death, Australia, 2011. Australian Bureau of Statistics, Australia. 2011. http://www.abs.gov.au/ausstats/abs@.nsf/Lookup/F25E446E1BE6C931CA257B2E000D729C?opendocument. Accessed 04/03/2014 2013.
- 15.Sanderson B, Hohlweck F, McMilan B. 3 pillars of a successful denials management program. Healthc Financ Manag J Healthc Financ Manag Assoc. 2008;62(9):74–80.Google Scholar
- 28.Menashe I, Maeder D, Garcia-Closas M, Figueroa JD, Bhattacharjee S, Rotunno M, et al. Pathway analysis of breast cancer genome-wide association study highlights three pathways and one canonical signaling cascade. Cancer Res. 2010;70(11):4453–9. doi: 10.1158/0008-5472.CAN-09-4502.CrossRefPubMedPubMedCentralGoogle Scholar
- 37.Lundstrom E, Sahlin L, Skoog L, Hagerstrom T, Svane G, Azavedo E, et al. Expression of syndecan-1 in histologically normal breast tissue from postmenopausal women with breast cancer according to mammographic density. Climacteric J Int Menopause Soc. 2006;9(4):277–82. doi: 10.1080/13697130600865741.CrossRefGoogle Scholar