CDH1 Gene rs1801552 C/T Polymorphism Increases Susceptibility to Esophageal Squamous Cell Carcinoma but Not to Gastric Cardiac Adenocarcinoma.

PURPOSE: The present study aimed to investigate whether the single nucleotide polymorphism (SNP) rs1801552 C/T in CDH1 gene is correlated with the risk of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), as a preliminary study. METHODS: The rs1801552 C/T polymorphism was genotyped by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 1316 cancer patients (810 ESCC and 506 GCA) and 1966 controls in north China. We performed two case-control studies, each of which included a population-based set and a hospital-based set. RESULTS: The data showed that the rs1801552 C/T polymorphism was associated with the risk of ESCC. Allelotype and genotype distributions of the rs1801552 C/T polymorphism in ESCC patients of high-incidence region and hospital were significantly different from that in their respective controls (p < 0.05). Compared with C/C genotype, T/T genotype increased the risk of ESCC in high-incidence region and hospital (age, sex, smoking status and family history of UGIC adjusted odds ratio (OR) = 1.79 and 2.10, 95% confidence interval (CI) = 1.23-2.60 and 1.10-4.04, respectively). Allelotype and genotype distributions of the rs1801552 C/T polymorphism in GCA patients were not significantly different from that in their controls, respectively (p > 0.05). CONCLUSIONS: The findings in the present pilot study suggest that the rs1801552 C/T polymorphism was associated with the risk of ESCC, but was not associated with the risk of GCA in high-incidence region and hospital.

The effect of polymorphisms in the promoter of the BIRC5 gene on the risk of oesophageal squamous cell carcinoma and patient's outcomes.

Baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) is an inhibitor of apoptosis proteins and plays a key role in apoptosis or programmed cell death. In the present study, we evaluated the effect of BIRC5 gene polymorphisms on the risk of developing oesophageal squamous cell carcinoma (ESCC) and patients' outcomes in a high-incidence population from northern China. A population-based case-control study was performed in 597 ESCC patients and 597 control subjects.Survival data were available for 211 patients who received platinum-based chemotherapy after surgery. Five polymorphisms (-31 C>G, -241 C>T, -625 G>C, -644 T>C and -1547 A>G) in the promoter of the BIRC5 gene were genotyped by the polymerase chain reaction-ligase detection reaction (PCR-LDR) method. Compared with the -31 CC genotype, the -31 CG/GG genotype of -31 C>G single nucleotide polymorphism (SNP) was associated with a significant elevated risk of ESCC [adjusted odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.07-1.84]. Interestingly, this association was stronger among females, younger patients and non-smokers in stratified analyses (adjusted OR = 1.72, 95% CI = 1.07-2.75; adjusted OR = 1.61, 95% CI = 1.10-2.36; adjusted OR = 1.80, 95% CI = 1.26-2.58, respectively]. Survival analyses showed that the T allele of -241 C>T SNP was associated with poor prognosis [hazard ratio (HR) = 2.99, 95% CI = 1.09-8.19) and that the C allele of -625 G>C SNP was associated with good prognosis (HR = 0.62, 95% CI = 0.38-0.99) in ESCC patients. The -31 C>G polymorphism may be involved in the development of ESCC, and the -241 C>T and -625 G>C polymorphisms may be useful prognostic markers for ESCC.

TIM-3 polymorphism is involved in the progression of esophageal squamous cell carcinoma by regulating gene expression.

The T-cell immunoglobulin and mucin domain containing molecule 3 (TIM-3), a crucial immune regulatory molecule, is an emerging immune checkpoint target for cancer therapy. Our study aimed to investigate the association between TIM-3 polymorphisms (rs10053538 C > A, rs10515746 C > A, and rs1036199 A > C) and the susceptibility and prognosis of esophageal squamous cell carcinoma (ESCC). We further detect the effects of polymorphisms on TIM-3 expression. Two independent case-control sets (population-based and hospital-based sets) were performed in total 994 ESCC patients and 998 controls. TIM-3 polymorphisms were genotyped by polymerase chain reaction-ligase detection reaction (PCR). Survival data were available for 198 patients who received platinum-based chemotherapy after surgery. The regulation on TIM-3 expression by the polymorphisms was investigated in 35 patients using real-time quantitative PCR. The association between mRNA level of TIM-3 and survival was detected by using Kaplan-Meier plotter database. We found that for rs10053538 C > A polymorphisms, A allele was associated with significant increased risk of ESCC (odds ratios [OR] = 1.34, 95%CI = 1.05-1.72), and CA/AA genotypes enhanced susceptibility to ESCC for smokers (adjusted OR = 1.61, 95%CI = 1.00-2.59). The patients with AA genotypes had significantly poor prognosis (adjusted HR = 4.98, 95%CI = 1.14-21.71). The patients carrying CA/AA genotypes had significantly higher mRNA levels of TIM-3 than those carrying the CC genotype. Furthermore, high mRNA level of TIM-3 had a shorter overall survival in patients (HR = 2.56, 95%CI = 1.04-6.28). For rs10515746 C > A and rs1036199 A > C polymorphisms, there were no statistical correlation with the progression of ESCC. These data demonstrate that rs10053538 C > A polymorphisms may be associated with the susceptibility and prognosis of ESCC patients through regulating expression of TIM-3.

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

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.

XPG Gene Polymorphisms and the Risk of Gastric Cardia Adenocarcinoma.

BACKGROUND: Polymorphisms in DNA repair genes can alter an individual's DNA repair capability and contribute to the risk of various cancers. AIMS: This study was designed to evaluate the association of single-nucleotide polymorphisms (SNPs) in the XPG gene with the risk of gastric cardia adenocarcinoma (GCA) in a high-incidence population in northern China. METHODS: Two SNPs from 431 GCA patients and 432 healthy controls were genotyped using the polymerase chain reaction/ligase detection reaction (PCR-LDR) method. RESULTS: The rs751402 C/T SNP T allele and the T/T genotype were associated with an increased risk of GCA in younger individuals (≤61 years) (odds ratio [OR] = 1.33 and 1.77, 95% confidence interval [CI] = 1.00-1.76 and 1.12-3.30, respectively). The rs873601 G/A SNP was not associated with susceptibility to GCA. CONCLUSIONS: Our findings indicate that the rs751402 C/T SNP has potential as a predictive marker for the risk of GCA and that carriers of the T/T genotype should receive periodic upper gastrointestinal fiber tests to facilitate the early detection and early treatment of GCA.