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Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

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  • Christopher Godina, Lund University
  • ,
  • Helga Tryggvadottir, Lund University
  • ,
  • Ana Bosch, Lund University
  • ,
  • Signe Borgquist
  • Mattias Belting, Lund University, Uppsala University
  • ,
  • Karolin Isaksson, Lund University
  • ,
  • Helena Jernström, Lund University

Purpose: Caveolin-1 (CAV1) has been implicated in breast cancer oncogenesis and metastasis and may be a potential prognosticator, especially for non-distant events. CAV1 functions as a master regulator of membrane transport and cell signaling. Several CAV1 SNPs have been linked to multiple cancers, but the prognostic impact of CAV1 SNPs in breast cancer remains unclear. Here, we investigated CAV1 polymorphisms in relation to clinical outcomes in breast cancer. Methods: A cohort of 1017 breast cancer patients (inclusion 2002–2012, Sweden) were genotyped using Oncoarray by Ilumina. Patients were followed for up to 15 years. Five out of six CAV1 SNPs (rs10256914, rs959173, rs3807989, rs3815412, and rs8713) passed quality control and were used for haplotype construction. CAV1 genotypes and haplotypes in relation to clinical outcomes were assessed with Cox regression and adjusted for potential confounders (age, tumor characteristics, and adjuvant treatments). Results: Only one SNP was associated with lymph node status, no other SNPs or haplotypes were associated with tumor characteristics. The CAV1 rs3815412 CC genotype (5.8% of patients) was associated with increased risk of contralateral breast cancer, adjusted hazard ratio (HRadj) 4.26 (95% CI 1.86–9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HRadj 2.24 (95% CI 1.24–4.04). No other genotypes or haplotypes were associated with clinical outcome. Conclusion: CAV1 polymorphisms were associated with increased risk for locoregional recurrence and contralateral breast cancer. These findings may identify patients that could derive benefit from more tailored treatment to prevent non-distant events, if confirmed.

TidsskriftBreast Cancer Research and Treatment
Sider (fra-til)335–347
Antal sider13
StatusUdgivet - jun. 2023

Bibliografisk note

Funding Information:
Open access funding provided by Lund University. The Swedish Cancer Society (CAN 20 0763), the Faculty of Medicine at Lund University, the Mrs Berta Kamprad Foundation, the South Swedish Health Care Region (Region Skåne ALF 40620), and the Skåne University Hospital fund. AB holds a young researcher award from ALF (Region Skåne). HT was funded by Region Skåne ST-ALF. The funders had no role in study design and conduct of the study, data collection and analysis, data interpretation, or manuscript preparation and decision to submit the manuscript for publication.

Publisher Copyright:
© 2023, The Author(s).

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