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Genetic variants in long noncoding RNA H19 contribute to the risk of breast cancer in a southeast China Han population

Authors Lin Y, Fu F, Chen Y, Qiu W, Lin S, Yang P, Huang M, Wang C

Received 17 November 2016

Accepted for publication 6 August 2017

Published 7 September 2017 Volume 2017:10 Pages 4369—4378


Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 4

Editor who approved publication: Prof. Dr. Geoffrey Pietersz

Yuxiang Lin,1,* Fangmeng Fu,1,* Yazhen Chen,1,* Wei Qiu,1 Songping Lin,1 Peidong Yang,1 Meng Huang,2 Chuan Wang1

1Department of Breast Surgery, Affiliated Union Hospital of Fujian Medical University, 2Fujian Center for Disease Control and Prevention, Fuzhou, China

*These authors contributed equally to this work

Abstract: The long noncoding RNA (lncRNA) H19 is a maternally expressed imprinted gene that plays important roles in tumorigenesis, progression, and metastasis. However, the association between polymorphisms on H19 and breast cancer (BC) susceptibility has remained obscure. In this case–control study, we assessed the interaction between two lncRNA H19 single-nucleotide polymorphisms (SNPs) (rs217727 C>T, rs2839698 C>T) and the risk of BC in a Chinese Han population. In total, 1,005 BC cases and 1,020 healthy controls were enrolled in this study. Correlations between genotypes and BC risk were evaluated by multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). False-positive report probability calculation was also utilized to identify false-positive associations. We observed that the rs217727 T variant was consistently significantly associated with an increased risk of BC in both codominant and dominant models (CT vs CC, OR 1.25, 95% CI 1.03–1.51; TT vs CC, OR 1.56, 95% CI 1.15–2.09; CT + TT vs CC, OR 1.31, 95% CI 1.09–1.57), and all associations remained significant after Bonferroni correction (P<0.025). Subsequent stratified analyses also revealed that associations between BC risk and rs217727 genotypes were more profound in patients with estrogen receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, and hormone receptor-positive–HER2-negative molecular subtypes (all passed the threshold for Bonferroni correction, P<0.005). These findings extend available data on the association of H19 polymorphisms and BC susceptibility. Based on these results, we encourage further large-scale studies and functional research to confirm our findings and better elucidate the underlying biological mechanisms.

Keywords: breast cancer, H19, lncRNA, polymorphisms, genetic susceptibility

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