Genetic polymorphisms of Cathepsin B are associated with gastric cancer risk and prognosis in a Chinese population

Article type: Research Article

Authors: Ma, Xiang^{a; 1} | Wang, Younan^{b; 1} | Fan, Hao^{a; 1} | Zhu, Chuming^{c; 1} | Chen, Wangwang^a | Li, Zengliang^a | Xiao, Jian^a | Ni, Peidong^a | Xu, Zekuan^a | Yang, Li^{a; c; *}

Affiliations: [a] Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [b] Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [c] Department of General Surgery, Liyang People’s Hospital, Liyang Branch Hospital of Jiangsu Province Hospital, Liyang, Jiangsu, China

Correspondence: [*] Corresponding author: Li Yang, Department of General Surgery, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, Jiangsu, 210029, China. Tel.: +86 25 83718836; E-mail: pwkyangli@njmu.edu.cn.

Note: [1] Xiang Ma, Younan Wang, Hao Fan and Chuming Zhu contributed equally to this study.

Abstract: BACKGROUND: Genetic polymorphisms are believed to represent a key aspect of predisposition to gastric cancer (GC). Therefore, considering the important role of Cathepsin B (CTSB) in promoting cancer onset and development, it could be very worthful to explore the function of CTSB-related genetic polymorphisms in GC. OBJECTIVE:In this study, we investigated the correlation of CTSB-related polymorphisms (rs9009A>T, rs6731T>C, rs1293303G>C, rs1874547C>T, rs3779659C>T, rs17814426C>T and rs148669985C>T) with GC risk and prognosis in a case-control study of 994 cases and 1000 controls. METHODS: All tag single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) sequencing technology. RESULTS: The results indicated rs9009, rs6731 and rs17814426 correlated with decreased risks of GC (HR = 0.97, p< 0.001; HR = 0.86, P= 0.019; HR = 0.85, P= 0.017; respectively). Stratification analysis further showed rs17814426 variant genotypes correlated with earlier T stage (p= 0.044). In addition, GC patients carrying the C allele of rs6371 had better overall prognosis (HR = 0.62, 95%CI = 0.44–0.88). CONCLUSION: Our results firstly suggested the importance of CTSB-related polymorphisms on GC which could predict GC risk and prognosis.

Keywords: Gastric cancer, Cathepsin B, Polymorphism, Susceptibility, Prognosis

DOI: 10.3233/CBM-203208

Journal: Cancer Biomarkers, vol. 32, no. 2, pp. 189-198, 2021