Breast Cancer-Related Lymphedema and Genetic Predisposition: A Systematic Review of the Literature

Background: Secondary lymphedema is a complication following breast cancer therapy and constitutes the main form of lymphedema in the western world. The purpose of the current study was to provide a clear overview of the genetic predisposition and secondary lymphedema. Methods and Results: A systematic search was performed between February and June 2017 in MEDLINE and Embase. Search terms included Genes, Genetic Predisposition to Disease, Lymphedema, Breast Cancer Lymphedema, Secondary Lymphedema, Breast Cancer-Related Lymphedema, and Humans. Only original articles regarding the possible relationship between genetic variation and the development of secondary lymphedema in humans were included in this review. A total of 459 records were collected. After removal of duplicates, non-topic-related publications,and records not presenting original data, six full-text studies were included. Associations between genetic factors and the development of secondary lymphedema were found for variations in HGF, MET, GJC2, IL1A, IL4, IL6, IL10, IL13, VEGF-C, NFKB2, LCP-2, NRP-2, SYK, VCAM1, FOXC2, VEGFR2, VEGFR3, and RORC. Conclusions: In patients with secondary lymphedema following breast cancer therapy, genetic variations were found in 18 genes. These compelling, although preliminary, findings may suggest a possible role for genetic predisposition in the development of lymphedema following breast cancer therapy. This notion may add to the classical, more mechanistic explanation of secondary lymphedema.