A Genetic Variant of rs145204276 in the Promoter Region of Long Noncoding RNA GAS5 Is Associated With a Reduced Risk of Breast Cancer

Association between lncRNA GAS5, MEG3, and PCAT-1 Polymorphisms and Cancer Risk: A Meta-Analysis

“…On the one hand, researchers observed that the del polymorphism rs145204276 may influence GAS5 transcriptional activity by affecting the methylation status of a CpG island in the promoter region of GAS5, which affects its tumorsuppressing function [34]. The rs145204276 del allele could also induce promoter activity by binding to SP1 and enhancing the expression level of lncRNA GAS5, which results in a higher risk factor for the development of breast cancer [17]. On the other hand, further studies showed that the overexpression of GAS5 induced by indel polymorphism rs145204276 can inhibit the expression of miR-221 and miR-182-5p, thereby reducing the proliferation, migration, and invasion properties of cancer [19].…”

“…The characteristics of the studies included in this metaanalysis are presented in Table 1. Among these articles, 11 involved rs145204276 in lncRNA GAS5 [13][14][15][16][17][18][19][20][21][22][23]. Within these 11 articles, 10 investigated Asian and one investigated Caucasian (Iran) ethnicity, and the source of controls was mainly population-based (9 studies).…”

“…However, the downregulation of GAS5 expression accelerates depletion of the YBX1 protein and decreases the expression of p21, thereby eliminating G1 arrest to control the proliferation of gastric cancer [12]. A functional 5-base pair (AGGCA/-) insertion/deletion (indel) polymorphism (rs145204276) that exists in the promoter region of lncRNA growth arrest-specific 5 (lncRNA GAS5) has been investigated in multiple cancer types [13][14][15][16][17][18][19][20][21][22][23]. A deletion (del) allele appears to enhance gene transcription activity when compared to an insertion (ins) allele [15].…”

Long Noncoding RNAs Involved in the Endocrine Therapy Resistance of Breast Cancer

“…Consistent with these findings, GAS5 is downregulated in breast tumors compared with normal tissues, and low expression of GAS5 is associated with poor overall survival in patients with breast cancer and TNBC [102,104,106]. Moreover, a recent study showed that an insertion (ins)/deletion (del) polymorphism located within the GAS5 promoter (rs145204276 AGGCA/-) affects the risk of breast cancer [109]. In that study, the rs145204276 ins/del and del/del genotypes, as well as the del allele, were associated with a reduced risk of breast cancer [109].…”

“…Moreover, a recent study showed that an insertion (ins)/deletion (del) polymorphism located within the GAS5 promoter (rs145204276 AGGCA/-) affects the risk of breast cancer [109]. In that study, the rs145204276 ins/del and del/del genotypes, as well as the del allele, were associated with a reduced risk of breast cancer [109]. As GAS5 expression is significantly higher in patients with breast cancer carrying the rs145204276 ins/del and del/del genotypes versus the rs145204276 ins/ins genotype carriers, and since the rs145204276 del allele increases the transcription of GAS5, this polymorphism may affect the risk of breast cancer by modulating GAS5 expression levels [109].…”