PARP1 Gene Polymorphisms and the Prognosis of Esophageal Cancer Patients from Cixian High-Incidence Region in Northern China.

Rong-Miao Zhou,Yan Li,Shi-Ru Cao,Na Wang,Xiang-Ran Huo,Chao-Xu Niu,Xi Huang

doi:10.31557/apjcp.2020.21.10.2987

Abstract

Objective:Poly (ADP-ribose) polymerase 1 (PARP1), as a key enzyme in the base excision repair pathway, plays a crucial role in tumorigenesis and progression. This study aimed to assess whether polymorphisms of PARP1 gene could be used as predictive biomarkers for the survival of esophageal squamous cell carcinoma (ESCC) patients from Cixian high-incidence region in northern China. Methods:In 203 ESCC patients with survival information, PARP1 rs1136410 T/C and rs8679 T/C single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction ligase detection reaction (PCR-LDR) method. All statistical analyses were performed using the SPSS ver. 22.0 software package (SPSS, Chicago, IL, USA). Results:The mean age ± standard deviation of the ESCC patients was 60.4 ± 7.9 years. There was no significant relation of sex, age, smoking status and upper gastrointestinal cancer family history with the survival time of the ESCC patients. The mean survival time of rs1136410 T/T, T/C and C/C genotype carriers were 43.3, 42.3 and 46.6 months, respectively. The rs1136410 was not associated with the survival time of the ESCC patients. For rs8679, the mean survival time of T/T genotype carriers was 43.7 months, which was not significantly different from that of the patients with T/C genotype (42.1 months).Conclusion:In Cixian high-incidence region from northern China, rs1136410 and rs8679 SNPs might not be used to predict survival of ESCC patients. There is a need to explore whether other SNPs of PARP1 gene have an effect on prognosis of ESCC patients.

Highlights

DNA repair system plays an important role in maintaining genomic integrity and stability
Age, smoking status and upper gastrointestinal cancer (UGIC) family history were not associated with the survival time of the esophageal squamous cell carcinoma (ESCC) patients (Table 1)
Age, smoking status and UGIC family history, rs1136410 and rs8679 single nucleotide polymorphisms (SNPs) were not associated with the survival time of ESCC patients (Table 2 and Table 3)

Summary

Introduction

DNA repair system plays an important role in maintaining genomic integrity and stability. Poly(ADP-ribose) polymerase 1 (PARP1) functions as a key enzyme in the BER pathway. PARP1 consists of three domains: N-terminal DNA-binding domain, central automodification domain, and C-terminal catalytic domain (Cottet et al, 2000). PARP1 can detect and bind the damaged DNA by its DNA-binding domain, catalyze poly(ADP-ribosyl)-ation of target protein including itself using nicotinamide adenine dinucleotide (NAD+) as a substrate, recruit other DNA repair proteins to the damaged site, and eventually jointly perform DNA damage repair (Caldecott et al, 1996; El-Khamisy et al, 2003; Kim et al, 2005; Shiokawa et al, 2005). Besides DNA repair function, PARP1 is implicated in other molecular and cellular processes such as chromatin modification, transcription and mitotic spindle formation (Kim et al, 2005). The application of PARP inhibitors in patients with various cancers has improved patients’ clinical outcome, which highlights the crucial role of PAPR1 in tumorigenesis and progression

Methods

Results

Conclusion