SDC4-rs1981429 and ATM-rs228590 may provide early biomarkers of breast cancer risk.

Abstract

In Australia, 13% of women are diagnosed with breast cancer (BC) in their lifetime with approximately 20,000 women diagnosed with the disease in 2021. 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 (SDC4) has been shown to downregulate AKT Serine/Threonine Kinase (AKT1) gene expression, while the ATM Serine/Threonine Kinase (ATM) gene has been found to inhibit this pathway upstream of AKT. We investigated single-nucleotide polymorphisms (SNPs) in HSPG and related genes SDC4, AKT1 and ATM 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-Cancer Council Queensland Breast Cancer Biobank (GU-CCQ BB) population. We identified that SDC4-rs1981429 and ATM-rs228590 may influence the development and progression of BC, having the potential to become biomarkers in early BC diagnosis and personalised treatment.

• Authors: Sofia I Vuorinen, Rachel K Okolicsanyi, Martina Gyimesi, Jacob Meyjes-Brown, Deepa Saini, Son H Pham, Lyn R Griffiths, Larisa M Haupt
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 149 Issue 8 Pg. 4563-4578 (Jul 2023) ISSN: 1432-1335 [Electronic] Germany
• PMID: 36152082 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s).

Chemical References

• Syndecan-4
• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• Heparan Sulfate Proteoglycans
• Biomarkers
• Serine
• SDC4 protein, human
• ATM protein, human
• Ataxia Telangiectasia Mutated Proteins

Topics

• Female
• Humans
• Breast Neoplasms (pathology)
• Syndecan-4 (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Australia
• Heparan Sulfate Proteoglycans (metabolism)
• Biomarkers
• Serine
• Ataxia Telangiectasia Mutated Proteins (metabolism)