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Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.

ABSTRACT: Genetic polymorphisms of NEIL1 and NEIL2 maybe change protein function, and increased carcinogenesis. In this study, seven NEIL1 SNPs and three NEIL2 SNPs were selected. 400 CSCCs, 400 CIN III, and 1200 normal healthy controls were genotyped by mismatch amplification PCR. mRNA and protein expression of NEIL2 was measured in 92 freshly-obtained CSCC tumor tissues. The association between homozygote CC genotype of NEIL2 rs804270 with susceptible risk was gradually increased in CIN III (OR?=?1.44) and CSCC (OR?=?2.22). Carriers of C-allele (GC?+?CC) at rs804270 had a high risk of CSCC (OR?=?1.46). The heterozygote GT genotype of rs8191664 was also closely related to the higher risk of CINIII (OR?=?1.59) and CSCC (OR?=?2.54). Carriers of T-allele (GT?+?TT) at rs8191664 had a high risk for CIN III (OR?=?1.55) and CSCC (OR?=?2.34). The genotypes of NEIL2 rs804270 (G/C) and rs8191664 (G/T) that were related to the higher risk for CIN III were CC-GG (OR?=?1.42) and CC-GT (OR?=?2.07). More notably, there was a greater risk for CSCC with the GC-GT (OR?=?1.91), CC-GG (OR?=?1.67), and CC-GT (OR?=?6.18) genotypes. NEIL2 mRNA expression in CSCCs with the rs804270-CC genotype was lower expression than those in CSCCs with the rs804270-GG and rs804270-GC genotypes. Similarly, NEIL2 protein expression was significantly decreased in CSCCs with the rs804270-CC genotype. In summary, the two genetic polymorphisms (rs804270 and rs8191664) of NEIL2 gene were significantly associated to the increased susceptibility of CIN III or CSCC. This increased susceptibility maybe due to altered NEIL2 repair activity through altered protein expression, or changed structure of the functional domain. The genotypes of GC-GT, CC-GG, and CC-GT of rs804270 and rs8191664 of NEIL2 gene could act as a genetic predictive biomarker of susceptibility to CIN III and CSCC.

SUBMITTER: Ye F

PROVIDER: S-EPMC7083954 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.

Ye Feng F Liu Jia J Wang Hanzhi H Chen Xiaojing X Cheng Qi Q Chen Huaizeng H

Scientific reports 20200320 1

Genetic polymorphisms of NEIL1 and NEIL2 maybe change protein function, and increased carcinogenesis. In this study, seven NEIL1 SNPs and three NEIL2 SNPs were selected. 400 CSCCs, 400 CIN III, and 1200 normal healthy controls were genotyped by mismatch amplification PCR. mRNA and protein expression of NEIL2 was measured in 92 freshly-obtained CSCC tumor tissues. The association between homozygote CC genotype of NEIL2 rs804270 with susceptible risk was gradually increased in CIN III (OR = 1.44) ...[more]

PMID: 32198476

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Project description:Despite a series of attempts during the last decades, the prognosis of esophageal squamous cell carcinoma (ESCC) remains poor. Different responses of individual tumors encouraged us to look for valuable prognostic markers. As a key regulator controlling the anabolic ketogenic pathway, 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) has been reported to play a crucial role in colorectal cancer and prostate cancer. However, its importance to ESCC has not been verified. Therefore, a large cohort retrospective study was planned, to investigate the relationship between HMGCS2 expression and ESCC prognosis. By adopting real-time polymerase chain reaction (PCR) and immunohistochemical (IHC) staining, HMGCS2 expression was examined in tissues of 300 ESCC patients with complete resection. Besides, the association between HMGCS2 protein expression and survival time was evaluated through chi-square test and Kaplan-Meier analysis. With the use of Cox-proportional hazards model, the prognostic impact of clinicopathologic variables and biomarker expression was evaluated. Compared with their non-tumor counterparts, HMGCS2 downregulation occurred in 65.5% and 37.6% of primary ESCCs on the mRNA and protein levels (P<0.001), respectively. On the protein level, HMGCS2 expression was associated with tumor cell differentiation (P=0.003), pT status (P=0.006), and TNM stage (P=0.010). In the down-HMGCS2 expression group, the 5-year overall survival (OS) and relapse-free survival (RFS) are poorer than those in the normal expression group (19 months vs 24 months, P=0.002; 13 months vs 17 months, P=0.007, respectively). According to the TNM stage, stratified analysis revealed that its discernibility on RFS was only pronounced in patients with advanced clinical stage (P=0.001). In addition, multivariate Cox regression analysis showed that HMGCS2 expression was an independent risk factor for RFS (P=0.032) instead of OS (P=0.099). The findings of this study provided the evidence that HMGSC2 represented a potential novel prognostic biomarker for ESCC patients.

Dataset Information

Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.

Publications

Cervical carcinoma risk associate with genetic polymorphisms of NEIL2 gene in Chinese population and its significance as predictive biomarker.

Similar Datasets

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