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Biomedicines 2018, 6(1), 23; https://doi.org/10.3390/biomedicines6010023

GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery in Breast Cancer Patients

1
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran
2
Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan 81746753461, Iran
3
School of Allied Health Sciences, Faculty of Health and Life Sciences, De Montfort University, Leicester LE1 9BH, UK
4
Cancer Prevention Research Centre, Isfahan University of Medical Sciences, Isfahan 8184917911, Iran
5
School of Biological Sciences, University of Portsmouth, Portsmouth PO1 2DY, UK
6
School of Pharmacy, Faculty of Health and Life Sciences, De Montfort University, Leicester LE1 9BH, UK
7
Department of Occupational Health Engineering, School of Health, Isfahan University of Medical Sciences, Isfahan 8174673461, Iran
8
Department of Biological Sciences, University of Chester, Chester CH1 4BJ, UK
*
Author to whom correspondence should be addressed.
Received: 31 December 2017 / Revised: 1 February 2018 / Accepted: 13 February 2018 / Published: 22 February 2018
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Abstract

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. View Full-Text
Keywords: connexin 37; secondary lymphedema; breast cancer; GJA4 gene; single nucleotide polymorphism (SNP) connexin 37; secondary lymphedema; breast cancer; GJA4 gene; single nucleotide polymorphism (SNP)
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Hadizadeh, M.; Mohaddes Ardebili, S.M.; Salehi, M.; Young, C.; Mokarian, F.; McClellan, J.; Xu, Q.; Kazemi, M.; Moazam, E.; Mahaki, B.; Bonab, M.A. GJA4/Connexin 37 Mutations Correlate with Secondary Lymphedema Following Surgery in Breast Cancer Patients. Biomedicines 2018, 6, 23.

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