Lymphedema is a condition resulting from mutations in various genes essential for lymphatic development and function, which leads to obstruction of the lymphatic system. Secondary
lymphedema is a progressive and incurable condition, most often manifesting after surgery for
breast cancer. Although its causation appears complex, various lines of evidence indicate that
genetic predisposition may play a role. Previous studies show that mutations in
connexin 47 are associated with secondary
lymphedema. We have tested the hypothesis that
connexin 37 gene mutations in humans are associated with secondary
lymphedema following
breast cancer surgery. A total of 2211
breast cancer patients were screened and tested for reference single nucleotide polymorphisms (SNPs) of the GJA4 gene (
gap junction protein alpha 4 gene). The results presented in this paper indicate that two SNPs in the
3' UTR (the three prime
untranslated region) of the GJA4 gene are associated with an increased risk of secondary
lymphedema in patients undergoing
breast cancer treatment. Our results provide evidence of a novel genetic
biomarker for assessing the predisposition to secondary
lymphedema in human
breast cancer patients. Testing for the condition-associated alleles described here could assist and inform treatment and post-operative care plans of
breast cancer patients, with potentially positive outcomes for the management of
disease progression.