Association of cytotoxic T‐lymphocyte associated protein 4 gene polymorphisms with the risk and prognosis of oesophageal cancer in a high‐incidence region from northern China

Abstract

The most important anti‐tumour immune response is mediated by T lymphocytes. Cytotoxic T lymphocyte‐associated protein 4 (CTLA4) plays a critical role in the immune surveillance against tumours as an inhibitory immune checkpoint molecule of T‐cell activation. This study was designed to explore the association of CTLA4 polymorphisms with the susceptibility to oesophageal squamous cell carcinoma (ESCC) and prognosis of patients with ESCC in a high‐incidence population from northern China. CTLA4 rs5742909 C/T and rs231775 G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase chain reaction–ligase detection reaction (PCR‐LDR) method in 577 ESCC patients and 580 controls. Upper gastrointestinal cancer family history increased the risk of ESCC (the sex‐, age‐ and smoking status‐adjusted OR = 1.383, 95%CI = 1.094–1.749). The genotype frequencies of these two SNPs in the patients with ESCC were similar to that in the controls. Survival analyses were conducted in 204 patients with ESCC with five‐year survival information. The mean survival time of ESCC patients with rs231775 SNP A/A genotype in age over 60 years group was 23.2 months, significantly shorter than that of those with G/G genotype (47.3 months). The A/A genotype was associated with increased death risk of patients with ESCC older than 60 years (adjusted HR = 4.544, 95%CI = 1.913–10.790). CTLA4 rs231775 SNP might be used as genetic marker of worse prognosis for patients with ESCC over 60 years in a high‐incidence population from northern China.

CTLA‐4 polymorphism contributes to the genetic susceptibility of epithelial ovarian cancer

“…Previously, there have been many reports about the association between rs5742909 C/T and cancer risk, but the results were still controversial. The meta‐analysis suggested that the T allele of rs5742909 C/T might increase an individual's susceptibility to gastric cancer, cervical cancer, and leukemia, 19–21 but it may not be related to the risk of esophageal cancer, lymphoid malignancy, and breast cancer 16,22,23 . However, the results show that the frequency of the T allele of rs5742909 C/T in epithelial ovarian cancer patients is significantly lower than that in the control group in the present study.…”

“…The metaanalysis suggested that the T allele of rs5742909 C/T might increase an individual's susceptibility to gastric cancer, cervical cancer, and leukemia, [19][20][21] but it may not be related to the risk of esophageal cancer, lymphoid malignancy, and breast cancer. 16,22,23 However, the results show that the frequency of the T allele of rs5742909 C/T in epithelial ovarian cancer patients is significantly lower than that in the control group in the present study. Women carrying the T allele may have a lower risk of developing epithelial ovarian cancer than those with the C allele.…”

“…Studies of non-small-cell lung cancer (NSCLC) and esophageal cancer have shown that rs5742909 C/T polymorphism may not be related to the patient's clinical prognosis. 16,31 However, one multicenter study showed that the rs231775 G/A polymorphism was associated with improved survival of epithelial ovarian cancer patients, particularly in patients with clear cell and endometrioid epithelial ovarian cancer. 30 Our study results suggested that rs231775 G/A, rs3087243 G/A, and rs5742909 C/T polymorphisms may not be associated with the clinical outcomes of epithelial ovarian cancer patients.…”

“…There are few reports on the impact of CTLA‐4 genetic variants on the clinical outcomes of cancer patients. Studies of non‐small‐cell lung cancer (NSCLC) and esophageal cancer have shown that rs5742909 C/T polymorphism may not be related to the patient's clinical prognosis 16,31 . However, one multicenter study showed that the rs231775 G/A polymorphism was associated with improved survival of epithelial ovarian cancer patients, particularly in patients with clear cell and endometrioid epithelial ovarian cancer 30 .…”

Mining genes related to microenvironment of esophageal squamous cell carcinoma based on TCGA database

“…In the PPI network of 68 DEGs, we found that some immune response genes are at the relative core of the PPI network, such as CD86, LCP2, TLR7, CSF1R, C1QA, IRF8, CTLA4 and so on. Among them, TLR7 has been reported to be overexpressed in ESCC [23] , and CTLA4 is related to the poor prognosis of patients with ESCC [24] . Finally, we searched the genes related to the risk and prognosis of ESCC from the CCGD-ESCC database.…”