Lymphatic and angiogenic candidate genes predict the development of secondary lymphedema following breast cancer surgery

• Published in: PloS one 2013-04, Vol.8 (4), p.e60164-e60164
• Main Authors: Miaskowski, Christine, Dodd, Marylin, Paul, Steven M, West, Claudia, Hamolsky, Deborah, Abrams, Gary, Cooper, Bruce A, Elboim, Charles, Neuhaus, John, Schmidt, Brian L, Smoot, Betty, Aouizerat, Bradley E
• Format: Article
• Language: English
• Subjects: Adult; Aged; Angiogenesis; Body mass; Body Mass Index; Body size; Breast cancer; Breast Neoplasms - surgery; Cancer; Cancer genetics; Cancer therapies; Cancer treatment; Cell adhesion; Cell adhesion molecules; Cross-Sectional Studies; Demographics; Endothelial growth factors; Female; Forkhead protein; Genes; Genetic Predisposition to Disease; Genotyping; Haplotypes; Humans; Lymph nodes; Lymphedema; Lymphedema - etiology; Lymphedema - genetics; Medicine; Middle Aged; Neuropilin; Neuropilin-2 - genetics; Patients; Polymorphism, Single Nucleotide - genetics; Protein-tyrosine kinase; Protein-Tyrosine Kinases - genetics; Rodents; Spectroscopy; Studies; Surgery; Tyrosine; Vascular cell adhesion molecule 1; Vascular Cell Adhesion Molecule-1 - genetics; Vascular endothelial growth factor; Vascular Endothelial Growth Factor C - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060164

The purposes of this study were to evaluate for differences in phenotypic and genotypic characteristics in women who did and did not develop lymphedema (LE) following breast cancer treatment. Breast cancer patients completed a number of self-report questionnaires. LE was evaluated using bioimpedance spectroscopy. Genotyping was done using a custom genotyping array. No differences were found between patients with (n = 155) and without LE (n = 387) for the majority of the demographic and clinical characteristics. Patients with LE had a significantly higher body mass index, more advanced disease and a higher number of lymph nodes removed. Genetic associations were identified for four genes (i.e., lymphocyte cytosolic protein 2 (rs315721), neuropilin-2 (rs849530), protein tyrosine kinase (rs158689), vascular cell adhesion molecule 1 (rs3176861)) and three haplotypes (i.e., Forkhead box protein C2 (haplotype A03), neuropilin-2 (haplotype F03), vascular endothelial growth factor-C (haplotype B03)) involved in lymphangiogensis and angiogenesis. These genetic associations suggest a role for a number of lymphatic and angiogenic genes in the development of LE following breast cancer treatment.