br Clinical Breast Cancer Vol No e Elsevier
Clinical Breast Cancer, Vol. 19, No. 3, e415-21 ª 2018 Elsevier Inc. All rights reserved. Keywords: Growth arrest-specific 5, Polymerase chain reaction (PCR)-polyacrylamide gel electrophoresis, Polymorphism, Quantitative PCR, Transcriptional activity
Breast cancer (BC) is the most common cancer, accounting for an expected 30% of all new cancer diagnoses in 2018.1 It is also the
Y.T. and Y.W. contributed equally to this work.
Department of Breast Surgery, the Third Affiliated Hospital of Kunming Medical University, Kunming Yunnan, P.R. China
Address for correspondence: Kai Zheng, MS, Department of Breast Surgery, Third Affiliated Hospital of Kunming Medical University, No 519 Kunzhou Rd, Kunming 650118, China
leading cause of cancer death from ages 20 to 59 years in women who are still raising and supporting families, making it a public health problem worldwide.1 Risk factors for BC included smoking con-sumption,2 high alcohol drinking,3 high-fat diet,4 and high levels of blood cholesterol.5 In addition to these environment factors, genetic factors have been shown to be involved in the occurrence and development of BC. Yan et al reported that a minor allele of C677T in methylenetetrahydrofolate reductase reduced activity of the enzyme, increased the level of homocysteine, and finally resulted in an increased risk of BC.6 Sawyer et al reported that BC patients with -161CC genotype in uridine glucuronosyltransferase 2B7 had a decreased epirubicin clearance and an increased risk of Grade 3 to 4 leukopenia, suggesting that the single nucleotide polymorphism
GAS5 Indel Polymorphism and Risk of Breast Cancer
(SNP) might be a predictor for drug metabolism, toxicity, and ef-ficacy in BC patients receiving chemotherapy.7 To date, a series of susceptibility genes of BC have been discovered. The precise etiol-ogy, however, remains poorly understood.
Long noncoding RNAs (lncRNAs), a set of noncoding RNAs more than 200 nucleotides in length, were recently identified to contribute important roles in a variety of biological processes.8-10 In BC, hundreds of lncRNAs were reported to be deregulated, and the deregulation led to aberrant gene T-5224 that were key events in the progression of BC.11-13 Current evidence showed that an lncRNA growth arrest-specific 5 (GAS5) was downregulated in BC, and the downregulation was not only associated with cell prolifer-ation and apoptosis, but also associated with clinical features of BC such as clinical stage, lymph node metastasis, and overall survival.14-
16 These findings indicate that lncRNA GAS5 might be a critical player in BC tumorigenesis.
Within the promoter region of lncRNA GAS5, a polymorphism rs145204276 AGGCA/- was found to be functional, with the deletion (del) allele increasing luciferase activity and expression levels of GAS5.17 Previously, the association of GAS5 rs145204276 polymorphism with cancer risk has been studied with conflicting results.17-21 Tao et al reported that the rs145204276 del allele increased the risk of hepatocellular carcinoma.17 In contrast, a reduced risk of the rs145204276 del allele was associated with gastric cancer,18,19 lung cancer,20 colorectal cancer,21 cervical squamous cell carcinoma,22 and osteosarcoma.23 To date, no report investigated the relationship between GAS5 rs145204276 and BC risk. In this study, we aimed to examine whether the rs145204276 in the promoter of lncRNA GAS5 contributes to the susceptibility of BC in a Chinese Han population. Furthermore, whether the SNP affected GAS5 expression level was also analyzed.
Patients and Methods
The study population consisted of 575 sporadic BC patients obtained from the Third Affiliated Hospital of Kunming Medical University between April 2013 and August 2017. All patients were breast adenocarcinoma with pathological confirmation of malig-nancy on resection. None of the patients received preoperative systemic chemotherapy or radiotherapy. The exclusion criteria for patients were as follows: (1) a history or family history of cancer; (2) recurrent BC; and (3) patients with breast hyperplasia. Clinical information relevant to the disease status was obtained from pa-tients’ medical charts, including positive or negative estrogen re-ceptor (ER) and progesterone receptor (PR), size of the primary tumor (T), presence and extent of regional lymph node metastasis (N), and absence or presence of distant metastasis (M). We also recruited 602 female controls visiting the same hospital for comprehensive medical checkup and matched them with cases according to age, ethnicity, age at menarche, and living area. We excluded controls who had a personal history or family history of any malignancy, breast hyperplasia, and/or breast mastitis. This study was reviewed and approved by the Ethical Committee of the Kunming Medical University. After informed constant was provided by each participant, blood and paraffin wax-embedded BC tissues were collected from the same patient.