Long non-coding RNA polymorphisms on 8q24 are associated with the prognosis of gastric cancer in a Chinese population

Abstract

Background Gastric cancer (GC) remains the third leading cause of cancer death in China. Although genome-wide association studies have identified the association between several single nucleotide polymorphisms (SNPs) on 8q24 and the risk of GC, the role of these SNPs in the prognosis of GC in Chinese populations has not yet been fully evaluated. Therefore, this study was conducted to explore the association between long non-coding RNA (lncRNA) polymorphisms on 8q24 and the prognosis of GC. Methods We genotyped 726 surgically resected GC patients to explore the association between eight SNPs in the lncRNAs CCAT1 (rs10087719, rs7816475), PCAT1 (rs1026411), PRNCR1 (rs12682421, rs13252298), and CASC8 (rs1562430, rs4871789, rs6983267) transcribed from the 8q24 locus and the prognosis of GC in a Chinese population. Results We found that the patients carrying rs12682421 AA genotypes survived for a shorter time than those with the GG/GA genotype (HR = 1.39, 95% confidence interval (CI) [1.09–1.78]). Compared with the CC/CT genotype, the TT genotype of rs1562430 was associated with an increased risk of death (HR = 1.38, 95% CI [1.06–1.80]). Furthermore, the results also identified the rs1026411 SNP as an independent prognostic factor for poor survival in GC patients. Patients carrying AA/AG variant genotypes had a 36% increased risk of death compared to those carrying the GG genotype (HR = 1.36, 95% CI [1.06–1.74]). These findings suggested that the rs12682421, rs1026411 and rs1562430 SNPs may contribute to the survival of GC and be prognostic markers for GC.

High Cancer Susceptibility Candidate 8 Expression Is Associated With Poor Prognosis of Pancreatic Adenocarcinoma: Validated Analysis Based on Four Cancer Databases

“…Most of the studies on CASC8 have focused on its polymorphism. CASC8 rs10505477 polymorphism was found to be greatly associated with gastrointestinal toxicity in small cell lung cancer (SCLC) and could serve as a possible risk marker for diagnosing lung cancer and could be used to forecast the response and toxicity of platinum-based treatment in lung cancer patients (Hu et al, 2016;Zhang et al, 2020). The rs10505477 is located in the intron of CASC8 which overlaps with the POU5F1B (POU class 5 homeobox 1 pseudogene 1) gene.…”

“…The rs10505477 is located in the intron of CASC8 which overlaps with the POU5F1B (POU class 5 homeobox 1 pseudogene 1) gene. A study on a Chinese population found that rs10505477 GA heterozygote in CASC8 was associated with a significantly lower survival rate in gastric cancer (Zhang et al, 2020). A meta-analysis for CASC8 in cancer showed that, compared with the individuals carrying the rs10505477 TT genotype, those with the TC or CC genotype had a decreased risk of cancer, whereas for rs7837328, the GA and AA genotypes were associated with increased risks of cancer as compared with the GG genotype.…”

“…A meta-analysis for CASC8 in cancer showed that, compared with the individuals carrying the rs10505477 TT genotype, those with the TC or CC genotype had a decreased risk of cancer, whereas for rs7837328, the GA and AA genotypes were associated with increased risks of cancer as compared with the GG genotype. These two polymorphisms might be associated with the risk of cancer (Hu et al, 2016;Zhang et al, 2020). A meta-analysis including 22 studies (47,003 cases and 45,754 controls) evaluated the rs6983267 of CASC8 in colorectal cancer, suggesting that the rs6983267 G > T polymorphism is a risk factor in Asians, Europeans, and Americans with European ancestry (Haerian et al, 2017).…”

“…It might be possible that CASC8 has similar functions because it is also involved in the development of several human tumors. Moreover, CASC8 polymorphisms (rs1447295 and rs10505477) have been reported as risk factors for some cancer types, such as gastric, hepatic, and breast cancers (Cui P. et al, 2018;Wu et al, 2019;Zhang et al, 2020). However, not much is known about the alteration of CASC8 expression in PAAD.…”

“…Based on the information available in four cancer databases (starBase, cBioPortal, circlncRNAnet, and UCSC Xena), we analyzed the CASC8 expression and its mutations, and the effect of this lncRNA on the survival in PAAD. We also analyzed the competing endogenous RNA (ceRNA) network, and CASC8 polymorphisms to unravel the mechanism underlying its role in the development of PAAD (Wu et al, 2018;Zhang et al, 2020). We finally evaluated the expression level of CASC8 in PAAD tissues and paired adjacent normal pancreatic tissues collected from 13 Chinese patients after surgical resection.…”