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BC is characterised by complex histological and genomic influences with recent advances in cancer biology improving early diagnosis and personalised treatment interventions. The Phosphatidyl-inositol-3-kinase\/Protein kinase B (PI3K\/AKT) pathway is essential in apoptosis resistance, cell survival, activation of cellular responses to DNA damage and DNA repair. Heparan sulfate proteoglycans (HSPGs) are ubiquitous molecules found on the cell surface and in the extracellular matrix with essential functions in regulating cell survival, growth, adhesion and as mediators of cell differentiation and migration. HSPGs, particularly the syndecans (SDCs), have been linked to cancers, making them an exciting target for anticancer treatments. In the PI3K\/AKT pathway, syndecan-4 (<jats:italic>SDC4<\/jats:italic>) has been shown to downregulate AKT Serine\/Threonine Kinase (<jats:italic>AKT1<\/jats:italic>) gene expression, while the ATM Serine\/Threonine Kinase (<jats:italic>ATM<\/jats:italic>) gene has been found to inhibit this pathway upstream of <jats:italic>AKT<\/jats:italic>. We investigated single-nucleotide polymorphisms (SNPs) in HSPG and related genes <jats:italic>SDC4<\/jats:italic>, <jats:italic>AKT1<\/jats:italic> and <jats:italic>ATM<\/jats:italic> and their influence on the prevalence of BC. SNPs were genotyped in the Australian Caucasian Genomics Research Centre Breast Cancer (GRC-BC) population and in the Griffith University\u2013Cancer Council Queensland Breast Cancer Biobank (GU-CCQ BB) population. We identified that <jats:italic>SDC4-<\/jats:italic>rs1981429 and <jats:italic>ATM-<\/jats:italic>rs228590 may influence the development and progression of BC, having the potential to become biomarkers in early BC diagnosis and personalised treatment.<\/jats:p>","DOI":"10.1007\/s00432-022-04236-2","type":"journal-article","created":{"date-parts":[[2022,9,24]],"date-time":"2022-09-24T11:03:16Z","timestamp":1664017396000},"page":"4563-4578","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["SDC4-rs1981429 and ATM-rs228590 may provide early biomarkers of breast cancer risk"],"prefix":"10.1007","volume":"149","author":[{"given":"Sofia I.","family":"Vuorinen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel K.","family":"Okolicsanyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Gyimesi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Meyjes-Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Saini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Son H.","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyn R.","family":"Griffiths","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Larisa M.","family":"Haupt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,9,24]]},"reference":[{"issue":"4","key":"4236_CR1","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1007\/s12282-017-0812-x","volume":"25","author":"K Araki","year":"2018","unstructured":"Araki K, Miyoshi Y (2018) Mechanism of resistance to endocrine therapy in breast cancer: the important role of PI3K\/Akt\/mTOR in estrogen receptor-positive, HER2-negative breast cancer. 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