PD-1 gene rs10204525 and rs7421861 polymorphisms are associated with increased risk and clinical features of esophageal cancer in a Chinese Han population

Abstract

Programmed death-1 (PD-1) polymorphisms have been associated with esophageal cancer risk. Here, the aims of this case-control study were to explore whether three PD-1 polymorphisms (rs10204525, rs7421861, and rs36084323) were related with the risk and clinical features of esophageal cancer in Chinese Han subjects (n = 814 cases and 961 controls). We found that rs10204525 and rs7421861, but not rs36084323, conferred increased susceptibility to esophageal cancer. Subgroup analysis revealed that all three loci increased the risk of esophageal cancer among men, and that rs10204525 and rs7421861 correlated with increased risk among patients ≥ 60 years old. The rs10204525 and rs7421861 polymorphisms were associated with higher TNM stage, and rs10204525 was associated with distant metastasis. The combination of smoking and either the rs10204525 or rs7421861 genotype conferred an increased risk to esophageal cancer, which is indicative of potential geneenvironment interactions. The rs10204525 and rs7421861 polymorphisms correlated with increased PD-1 gene and protein levels, and Kaplan-Meier survival curves showed higher PD-1 gene expression was related to poorer overall survival. These data indicate the rs10204525 and rs7421861 polymorphisms of PD-1 gene confer an increased risk of esophageal cancer among Chinese Han individuals.

Immune Checkpoint Molecules—Inherited Variations as Markers for Cancer Risk

“…However, two of them ( 163 , 174 ) showed a decreased risk for PD-1.6 G/G individuals (OR = 0.59 and OR = 0.68, respectively) (in the study by Qiu et al. ( 174 ) deviation from HWE was observed in controls), while Zang et al ( 175 ) reported the opposite effect—carriage of PD-1.6*G allele was associated with increased risk of esophageal cancer (OR = 1.26). Moreover, in this study individuals with PD-1.6 G/G genotype and carriers of PD-1.6*G allele had, respectively, higher TNM stage (OR = 1.81) and higher risk of distant metastasis (OR = 1.67) ( 175 ).…”

“…( 174 ) deviation from HWE was observed in controls), while Zang et al ( 175 ) reported the opposite effect—carriage of PD-1.6*G allele was associated with increased risk of esophageal cancer (OR = 1.26). Moreover, in this study individuals with PD-1.6 G/G genotype and carriers of PD-1.6*G allele had, respectively, higher TNM stage (OR = 1.81) and higher risk of distant metastasis (OR = 1.67) ( 175 ). Taking into consideration the inconsistent results presented above as well as the fact that there was no evidence of association between this SNP and overall cancer risk—more research on this issue is needed.…”

“…As for particular types of gastrointestinal cancer, according to our best knowledge, in the literature there are only three studies ( 163 , 174 , 175 ) aimed at investigating the PDCD1 SNPs as potential risk factors for esophageal cancer, more precisely esophageal squamous cell carcinoma (ESCC). In all three studies the PD-1.6 was suggested to be associated with susceptibility to esophageal cancer.…”

“…The results regarding the rs7421861T>C are also inconsistent. Some evidence suggests increased risk of esophageal cancer (OR = 1.24) and higher TNM stage (OR = 1.37) for rs7421861*T allele carriers (decreased for individuals with rs7421861 C/C genotype) ( 175 ) while another shows no association of this SNP with ESCC at al. ( 174 ).…”

“…This observation is not in line with the results of analysis regarding gastrointestinal cancers and overall cancer risk, demonstrating association of the PD-1.5 T/T genotype with decreased susceptibility. Also, the PD-1.1 was investigated in the context of ESCC ( 163 , 175 ), however, there was no evidence for association between this SNP and susceptibility to ESCC.…”