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

Godina, Christopher LU orcid ; Tryggvadottir, Helga LU ; Bosch, Ana LU ; Borgquist, Signe LU ; Belting, Mattias LU ; Isaksson, Karolin LU and Jernström, Helena LU (2023) In Breast Cancer Research and Treatment 199(2). p.335-347
Abstract

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... (More)

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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Caveolin-1, Contralateral breast cancer, Genotype, Locoregional breast cancer recurrence
in
Breast Cancer Research and Treatment
volume
199
issue
2
pages
13 pages
publisher
Springer
external identifiers
  • pmid:37017811
  • scopus:85151533966
ISSN
0167-6806
DOI
10.1007/s10549-023-06919-x
language
English
LU publication?
yes
id
9e1dc678-15f6-45c7-bcb5-84c45abfe970
date added to LUP
2023-05-23 13:21:19
date last changed
2024-04-19 22:08:06
@article{9e1dc678-15f6-45c7-bcb5-84c45abfe970,
  abstract     = {{<p>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 (HR<sub>adj</sub>) 4.26 (95% CI 1.86–9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HR<sub>adj</sub> 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.</p>}},
  author       = {{Godina, Christopher and Tryggvadottir, Helga and Bosch, Ana and Borgquist, Signe and Belting, Mattias and Isaksson, Karolin and Jernström, Helena}},
  issn         = {{0167-6806}},
  keywords     = {{Caveolin-1; Contralateral breast cancer; Genotype; Locoregional breast cancer recurrence}},
  language     = {{eng}},
  number       = {{2}},
  pages        = {{335--347}},
  publisher    = {{Springer}},
  series       = {{Breast Cancer Research and Treatment}},
  title        = {{Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer}},
  url          = {{http://dx.doi.org/10.1007/s10549-023-06919-x}},
  doi          = {{10.1007/s10549-023-06919-x}},
  volume       = {{199}},
  year         = {{2023}},
}