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

The growth arrest-specific 5 (GAS5) rs145204276 AGGCA/-polymorphism was analyzed in 575 patients with sporadic breast cancer (BC) and 602 controls to test the association between the polymorphism and BC risk. The rs145204276 del allele might protect against the development of BC via inducing the promoter activity by binding to transcriptional factor specificity protein 1, and finally resulting in higher levels of GAS5. Introduction: Growth arrest-specific 5 (GAS5), downregulated in breast cancer (BC), functions as a tumor suppressor by affecting tumor growth and cell apoptosis in vivo and in vitro. This study was designed to determine whether an insertion (ins)/deletion (del) polymorphism (rs145204276 AGGCA/-) in the promoter region of GAS5 was a susceptibility gene to the occurrence of BC. Patients and Methods: A hospital-based case-control study was conducted and the GAS5 rs145204276 genotype was analyzed in 575 sporadic BC patients and 602 controls to test the association between the polymorphism and BC risk. Further functional analysis was performed to evaluate the effect of the polymorphism on the promoter activity and GAS5 expression levels using quantitative polymerase chain reaction and dual luciferase reporter assay. Results: The prevalence of BC was lower in carriers with rs145204276 ins/del and del/del genotypes compared with those with ins/ins genotype (adjusted odds ratio [OR], 0.74; 95% confidence interval [CI], 0.58-0.92; P = .009). An allelic test for association with BC was also significant (del vs. ins: adjusted OR, 0.78; 95% CI, 0.65-0.93; P = .007). Genotype-phenotype analysis revealed that individuals with rs145204276 ins/del and del/del genotypes expressed significantly higher levels of GAS5. Luciferase reporter analysis revealed that rs145204276 del allele enhanced the promoter activity of GAS5. Conclusion:The rs145204276 del allele might protect against the development of BC via inducing the promoter activity by binding to transcriptional factor specificity protein 1, and finally resulting in higher levels of GAS5. (C) 2018 Elsevier Inc. All rights reserved.