Hadizadeh Mahrooyeh, Mohaddes Ardebili Seiied Mojtaba, Salehi Mansoor, Young Chris, Mokarian Fariborz, McClellan James, Xu Qin, Kazemi Mohammad, Moazam Elham, Mahaki Behzad, Ashrafian Bonab Maziar
Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz 5166614766, Iran.
Department of Genetics and Molecular Biology, Isfahan University of Medical Sciences, Isfahan 81746753461, Iran.
Biomedicines. 2018 Feb 22;6(1):23. doi: 10.3390/biomedicines6010023.
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 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 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.
淋巴水肿是一种由多种对淋巴系统发育和功能至关重要的基因突变引起的疾病，会导致淋巴系统阻塞。继发性淋巴水肿是一种进行性且无法治愈的疾病，最常见于乳腺癌手术后。尽管其病因似乎很复杂，但各种证据表明遗传易感性可能起作用。先前的研究表明，连接蛋白47的突变与继发性淋巴水肿有关。我们检验了这样一个假设，即人类连接蛋白37基因突变与乳腺癌手术后的继发性淋巴水肿有关。总共对2211名乳腺癌患者进行了筛查，并检测了该基因（间隙连接蛋白α4基因）的参考单核苷酸多态性（SNP）。本文给出的结果表明，该基因3'非翻译区（3'UTR）中的两个SNP与接受乳腺癌治疗的患者发生继发性淋巴水肿的风险增加有关。我们的结果为评估人类乳腺癌患者继发性淋巴水肿易感性的一种新型遗传生物标志物提供了证据。检测此处所述的与疾病相关的等位基因可为乳腺癌患者的治疗和术后护理计划提供帮助并提供信息，对疾病进展的管理可能产生积极结果。
