Background: Lymphedema is a debilitating and progressive clinical entity characterized by abnormal accumulation of lymph and fluid in the extracellular space. Most of the cases in western population are related to cancer treatment. Research on cancer-related lymphedema (CRL) is mounting for potential risk factors associated to disease, treatment, or patient. However, only a few cancer survivors with the same risk factors will develop lymphedema, giving rise to the hypothesis that inherited genetic susceptibility may play a role in CRL pathophysiology. This systematic review aimed to identify, critically appraise, and summarize the results of individual studies that have examined the genetic predisposition to CRL. Methods and Results: A comprehensive literature search in MEDLINE, Cochrane, and Scopus was conducted from inception to February 2021. Screening of available studies and quality of the included studies were carried out by two reviewers independently. Eight studies fulfilled eligibility criteria, involving 573 women with breast-cancer related lymphedema (BCRL) among 1,481 participants. Associations between the development of CRL and genetic factors were observed for variations in 23 genes in patients with BCRL. Conclusions: The present systematic review is the first examining specifically the genetic predisposition in CRL. Statistically significant genetic variations were found in 23 genes in patients with BCRL. These preliminary findings highlight the importance of genetic susceptibility in the development of CRL, altering the traditional perception of its iatrogenic etiology. Additional well-designed research, aiming toward the confirmation of previously performed genetic analyses and functional assessment of the genetic variations, is required.
Keywords: cancer related lymphedema; genes; genetic predisposition; secondary lymphedema; systematic review.