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.

Prognostic value of soluble factors of angiogenesis and adhesion processes in head and neck squamous cell carcinomas

“…Most of the studies concluded that augmented levels of VCAM-1 are associated with advanced oncogenesis, as for instance in stage 4 breast cancer patients [19,21]. Furthermore, the development of lymphedema after breast cancer surgery also correlated with VCAM expression and VCAM was markedly increased after a dose-dense regimen of chemotherapy [21]. Similar findings could be obtained in colorectal cancer patients, where VCAM was revealed as a biomarker for overall survival and post-operative recurrence [20].…”

“…Recently conducted studies revealed the importance of adhesion process in tumor biology [17]. The existence of adhesion molecules in circulation has been shown in head and neck carcinomas [15][16][17][18][19][20][21]. One of the most important adhesion molecules is the vascular cell adhesion molecule.…”

“…Studies reported on an upregulation of VCAM-1 after VEGF stimulation of endothelial cells [20]. Most of the studies concluded that augmented levels of VCAM-1 are associated with advanced oncogenesis, as for instance in stage 4 breast cancer patients [19,21]. Furthermore, the development of lymphedema after breast cancer surgery also correlated with VCAM expression and VCAM was markedly increased after a dose-dense regimen of chemotherapy [21].…”

“…Adhesion molecules such as vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), and N-CAM like adhesion molecule have been described [15][16][17][18][19][20][21]. All of these molecules are thought to play a role in tumor invasiveness and tumor aggression but the mechanism of this function is still not clear [15][16][17][18][19][20][21]. Adhesion molecules are believed to take part in the process of metastasis but here again the exact mechanism is not clear.…”

“…The possible roles of soluble adhesion molecules in the prognosis of head and neck carcinoma deserve further elucidation and evaluation. However, some studies show that the level of circulating adhesion molecules such as VCAM is higher in cancer patients than in the normal population [15][16][17][18][19][20][21].…”