title: Lymphatic and angiogenic candidate genes predict the development of secondary lymphedema following breast cancer surgery.
abstract: 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.
authors.affiliation: Department of Physiological Nursing, University of California San Francisco, San Francisco, California, United States of America. chris.miaskowski@nursing.ucsf.edu
authors.forename: Christine
authors.initials: C
authors.lastname: Miaskowski
authors.forename: Marylin
authors.initials: M
authors.lastname: Dodd
authors.forename: Steven M
authors.initials: SM
authors.lastname: Paul
authors.forename: Claudia
authors.initials: C
authors.lastname: West
authors.forename: Deborah
authors.initials: D
authors.lastname: Hamolsky
authors.forename: Gary
authors.initials: G
authors.lastname: Abrams
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Cooper
authors.forename: Charles
authors.initials: C
authors.lastname: Elboim
authors.forename: John
authors.initials: J
authors.lastname: Neuhaus
authors.forename: Brian L
authors.initials: BL
authors.lastname: Schmidt
authors.forename: Betty
authors.initials: B
authors.lastname: Smoot
authors.forename: Bradley E
authors.initials: BE
authors.lastname: Aouizerat
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000601:surgery*; D003430:Cross-Sectional Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008209:Lymphedema / Q000209:etiology / Q000235:genetics*; D008875:Middle Aged; D039943:Neuropilin-2 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics
chemical_list: D039943:Neuropilin-2; C467486:VEGFC protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042582:Vascular Endothelial Growth Factor C; D011505:Protein-Tyrosine Kinases