ArticleClinical cancer research : an official journal of the American Association for Cancer Research2012
Connexin 47 mutations increase risk for secondary lymphedema following breast cancer treatment.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 113 citations in OpenAlex.
- Factors influencing the incidence of postoperative lymphedema in patients with locally advanced triple-negative breast cancer.World journal of surgical oncology · 2026Article
- Hierarchical Requirement for Endothelial Cell Connexins Cx37, Cx47, Cx43, and Cx45 in Lymphatic Valve Function.Function (Oxford, England) · 2025Article
- Predictors of the Efficacy of Lymphedema Decongestive Therapy.Medicina (Kaunas, Lithuania) · 2025Review
- Characteristics and advances in signaling pathways, cellular communication, cell junctions, and oxidative stress in lymphedema.Frontiers in cell and developmental biology · 2025Review
- Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.JCI insight · 2024Article
- The Role of Inflammation in Lymphedema: A Narrative Review of Pathogenesis and Opportunities for Therapeutic Intervention.International journal of molecular sciences · 2024Review
- Demystifying vascularized lymph node transfers and lymphatico-venous anastomoses.Annals of translational medicine · 2024Review
- A 1D model characterizing the role of spatiotemporal contraction distributions on lymph transport.Scientific reports · 2023Article
- Description of Phenotypic Heterogeneity in aMolecular syndromology · 2023Article
- Mechanisms of Diseases Associated with Mutation in GJC2/Connexin 47.Biomolecules · 2023Review
- Lymphatic Clearance and Pump Function.Cold Spring Harbor perspectives in medicine · 2023Review
- Immediate lymphatic reconstruction for the prevention of breast cancer-related lymphedema: an experience highlighting the importance of lymphatic anatomy.Plastic and aesthetic research · 2023Article
- BiallelicJournal of medical genetics · 2023Article
- Lymphatic Collecting Vessels in Health and Disease: A Review of Histopathological Modifications in Lymphedema.Lymphatic research and biology · 2022Review
- Secondary lymphedema from cancer therapy.Clinical & experimental metastasis · 2022Review
- Pharmacological Treatment of Secondary Lymphedema.Frontiers in pharmacology · 2022Review
- Differential Expression ofCancers · 2021Article
- Lymphatic Connexins and Pannexins in Health and Disease.International journal of molecular sciences · 2021Review
- Review
- Abnormal lymphatic phenotype in a CRISPR mouse model of the human lymphedema-causing Connexin47 R260C point mutation.Lymphology · 2021Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
purposeSecondary lymphedema is a frequent complication of breast cancer associated with surgery, chemotherapy, or radiation following breast cancer treatment. The potential contribution of genetic susceptibility to risk of developing secondary lymphedema following surgical trauma, radiation, and other tissue insults has not been studied. EXPERIMENTAL
designTo determine whether women with breast cancer and secondary lymphedema had mutations in candidate lymphedema genes, we undertook a case-control study of 188 women diagnosed with breast cancer recruited from the University of Pittsburgh Breast Cancer Program (http://www.upmccancercenter.com/breast/index.cfm) between 2000 and 2010. Candidate lymphedema genes, GJC2 (encoding connexin 47 [Cx47]), FOXC2, HGF, MET, and FLT4 (encoding VEGFR3), were sequenced for mutation. Bioinformatics analysis and in vitro functional assays were used to confirm significance of novel mutations.
resultsCx47 mutations were identified in individuals having secondary lymphedema following breast cancer treatment but not in breast cancer controls or normal women without breast cancer. These novel mutations are dysfunctional as assessed through in vitro assays and bioinformatics analysis and provide evidence that altered gap junction function leads to lymphedema.
conclusionsOur findings challenge the view that secondary lymphedema is solely due to mechanical trauma and support the hypothesis that genetic susceptibility is an important risk factor for secondary lymphedema. A priori recognition of genetic risk (i) raises the potential for early detection and intervention for a high-risk group and (ii) allows the possibility of altering surgical approach and/or chemo- and radiation therapy, or direct medical treatment of secondary lymphedema with novel connexin-modifying drugs.
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Registered trials
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