Influence of a 5-bp Indel Polymorphism at Promoter of the GAS5 lncRNA and Risk of Breast Cancer.

Rafat Sharifi,Zivar Salehi,Laleh Mirzanezhad,S Shirin Shahangian,Soheila Talesh Sasani,Farhad Mashayekhi

doi:10.31557/apjcp.2020.21.12.3705

Abstract

Long non-coding RNAs (lncRNAs) are RNA molecules (>200 nucleotides in length) with no protein-coding capacity. Recent studies have demonstrated that lncRNAs involve in the regulation of their target genes at transcriptional, post-transcriptional and epigenetic levels. The aim of this case-control study was to explore whether growth arrest-specific 5 (GAS5) lncRNA 5-bp Ins/Del (rs145204276) polymorphism is involved in the breast cancer susceptibility. A total of 170 cases and 220 age matched controls were recruited in this study. GAS5 lncRNA polymorphism was genotyped using tetra primers amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method. Statistical analysis was performed using SPSS. The distribution of the genotype ins/ins, ins/del and del/del were %75.29, 21.76% and 2.94% and 52.27%, 39.55% and 8.81% in the cases and controls, respectively. The ins/del or del/del genotype had a significantly decreased risk of breast cancer as compared with the ins/ins genotype under a codominant model (OR=0.38, 95%CI 0.24-0.60, p=0.0001; OR= 0.25, 95%CI 0.09-0.69, p=0.008, respectively). Moreover, the deletion allele of this polymorphic site is associated with a protective effect (OR=0.41, 95%CI 0.28-0.60, p=0.0001). Our study provided the first evidence that the deletion allele of GAS5 rs145204276 may have a protective role in mediating individual susceptibility to breast cancer. However, further comprehensive studies are warranted in a larger sample.

Highlights

Breast cancer ranks the first most common type of malignancies among females worldwide (Behjati et al, 2005; Torre et al, 2015)
3708 Asian Pacific Journal of Cancer Prevention, Vol 21. In this case-control study, we studied the impact of growth arrest-specific 5 (GAS5) Long non-coding RNAs (lncRNAs) polymorphism in breast cancer susceptibility in Iranian population
This is the first study in Iranian population showing a significant association between the GAS5 lncRNA del allele and decreased breast cancer susceptibility

Summary

Introduction

Breast cancer ranks the first most common type of malignancies among females worldwide (Behjati et al, 2005; Torre et al, 2015). Breast cancer accounts for approximately 450,000 dead worldwide every year (Coughlin and Ekwueme, 2009). The etiology of breast cancer comprises interactions of genetic factors and multiple environmental components. Many variants of different genes have been associated with breast cancer risk worldwide; including p53 (Murphy et al, 2017), IL1 (Zuo et al, 2018), SEEP1 (Mohammaddoust et al, 2018). Includ¬ing lower age of menarche, late age of first pregnancy, fewer pregnancies, shorter or no periods of breastfeeding, later menopause, obesity, alcohol consumption, inactivity, and hormone replacement therapy (HRT), have been reported to contribute to the pathogenesis of breast cancer (Colditz and Bohlke, 2014). The underlying etiological mechanisms of breast cancer are not fully understood

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