Study Finds Genetic Link to Lymphedema

Study Finds Genetic Link to Lymphedema

Breast cancer survivors who develop lymphedema after treatment for their cancer have a genetic predisposition to do so, according to a new study published in PLoS ONE. The study also found that the risks of developing lymphedema increased significantly for women who had more advanced breast cancer at the time of their diagnosis, a high body mass index, or increased number of lymph nodes removed.

The results of the study are hypothesis generating, but if the link is confirmed in other studies and a mechanism for the development of lymphedema is found, the hope is that a therapy will be found as well, lead author Christine Miaskowski, PhD, from the University of California, San Francisco, told Medscape Medical News.


The exact prevalence of lymphedema after breast cancer treatment is unknown, but up to 56% of women who undergo breast cancer surgery develop lymphedema within 2 years, according to the National Cancer Institute, Dr. Miaskowski said.

Four Genes Involved

The study evaluated 155 women with lymphedema in an upper extremity (arm or fingers) and 387 women with no lymphedema. The women underwent bioimpedance spectroscopy to measure their lymphedema and also had genomic DNA extracted from blood samples.

The researchers found associations between lymphedema and 4 genes known to play a role in the development of lymphedema (lymphocyte cytosolic protein 2 [rs315721], neuropilin-2 [rs849530], protein tyrosine kinase [rs158689], and vascular cell adhesion molecule 1 [rs3176861]) and 3 haplotypes (Forkehead box protein C2 [haplotype A03], neuropilin02 [haplotype F03], and vascular endothelial growth factor C [haplotype B03]) involved in lymphangiogenesis and angiogenesis.

"These findings are of no use to clinicians just yet," Dr. Miaskowski said. "We need to confirm our findings in other studies, and if we do, the hope is that we will discover the mechanism and then a therapy."

Currently some half a million breast cancer survivors have lymphedema in the United States. "This is not an insignificant problem, and women suffer greatly. My dream is if we can figure out the genetic profile and identify women at high risk, we could do some prophylaxis, perhaps work immediately after surgery with these women, promote exercise, avoid trauma, and my guess is we could reduce the incidence," she said.

The study was funded by the National Cancer Institute of the National Institutes of Health. Dr. Miaskowski has disclosed no relevant financial relationships.

PLoS ONE. 20138:e60164. 

Lymphatic and Angiogenic Candidate Genes Predict the Development of Secondary Lymphedema following Breast Cancer Surgery:

Christine Miaskowski mail, Marylin Dodd, Steven M. Paul, Claudia West, Deborah Hamolsky, Gary Abrams, Bruce A. Cooper, Charles Elboim, John Neuhaus, Brian L. Schmidt,    Betty Smoot, Bradley E. Aouizerat