Article Abstract

A novel functional indel polymorphism within long non-coding RNAs growth arrest specific 5 conferred risk for cervical squamous cell carcinoma in Chinese Han populations

Authors: Zhansheng Zhu, Lanjun Feng, Futian Li, Yuanzhi Xue, Chaoyang Li, Huiping Wang

Abstract

Background: Growth arrest specific 5 (GAS5) has been reported as a tumor repressor in multiple cancers, but the role of the indel polymorphism rs145204276 within GAS5 in cervical squamous cell carcinoma (CSCC) susceptibility has not been well established yet.
Methods: A hospital based case-control study in Shehong and Xuzhou centers was performed to evaluate the potential association of the indel polymorphism rs145204276 within GAS5 with CSCC risk, and further in vivo and in vitro assays were applied to confirm the plausible association.
Results: When taking ins/ins genotype as reference in codominant model, ins/del genotype confers a slightly increased risk for CSCC [odds ratio (OR) =1.27, 95% confidence interval (CI): 1.04–1.52, P=0.02], the homozygous del/del genotype shows an increased risk for CSCC (OR =2.24, 95% CI: 1.60–2.97, P<0.00001), linear trend test confirms that it has the linear correlation between the polymorphism and CSCC risk (Ptrend<0.00001). In recessive model, the homozygous del/del genotype shows an increased risk for CSCC (OR= 1.98, 95% CI: 1.42–2.66, P<0.00001). Similar trends are observed in dominant model and additive model. Further genotype and phenotype correlation confirmation is applied in vivo and in vitro, and stratified analysis has revealed that the relation is more marked in subjects with postmenopausal status, tobacco consumption, or senior age (>49 years). Furthermore, the association of the polymorphism with CSCC risk is salient in cases with tumor stage IV (P=0.001).
Conclusions: We have found that the novel functional indel polymorphism rs145204276 is associated with CSCC risk. Replication investigations and further functional assays are required for the current investigation.

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