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SDC4-rs1981429 and ATM-rs228590 may provide early biomarkers of breast cancer risk
Ist Teil von
Journal of cancer research and clinical oncology, 2023-07, Vol.149 (8), p.4563-4578
Ort / Verlag
Berlin/Heidelberg: Springer Berlin Heidelberg
Erscheinungsjahr
2023
Link zum Volltext
Quelle
MEDLINE
Beschreibungen/Notizen
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.