Programmed death-1 polymorphisms is associated with risk of esophagogastric junction adenocarcinoma in the Chinese Han population: A case-control study involving 2,740 subjects.

Weifeng Tang,Mingqiang Kang,Yafeng Wang,Jihong Lin,Yu Chen,Chao Liu,Jiangbo Lin,Shuchen Chen

doi:10.18632/oncotarget.17338

Weifeng Tang, Mingqiang Kang + Show 6 more

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https://doi.org/10.18632/oncotarget.17338

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Abstract

Single nucleotide polymorphisms (SNPs) in Programmed cell death 1 (PD-1) gene may contribute to the development of cancer. In this study, we selected PD-1 rs10204525 T>C, rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and designed a hospital-based case-control study to determine the potential relationship between these functional SNPs in PD-1 gene and esophagogastric junction adenocarcinoma (EGJA) risk. A total of 1,063 EGJA patients and 1,677 controls were enrolled from Eastern Chinese Han population. SNPscanTMgenotyping assay was used to analyze the genotyping of PD-1 polymorphisms. We found that PD-1 rs7421861 A>G polymorphism was associated with the development of EGJA. However, PD-1 rs2227982 A>G polymorphism was a protective factor for EGJA. In addition, PD-1 rs36084323 CC homozygote genotype might be associated with a borderline decreased risk of EGJA. In a subgroup analysis, a decreased risk of EGJA in never drinking and never smoking groups was identified. Haplotype comparison analysis suggested that PD-1 Trs10204525Grs2227982C36084323Ars7421861 haplotype significantly decreased the risk of EGJA. However, Trs10204525Grs2227982C36084323Grs7421861 haplotype in PD-1 gene may confer risk to EGJA. In conclusion, our study highlights rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms and haplotypes in PD-1 gene, especially within the intron region, are significantly associated with the risk of EGJA. Further case-control studies with larger sample size and detailed gene-environmental data to replicate these findings in different populations are needed to validate our conclusion.

Highlights

A steady decline of gastric carcinoma (GC) incidence has been observed worldwide, primarily as a result of a reduction in distal GC [1]
We found that Programmed cell death 1 (PD-1) rs7421861 A>G polymorphism was associated with the development of esophagogastric junction adenocarcinoma (EGJA)
We found that TGCA haplotypes with the order of PD-1 rs10204525 T>C, rs2227982 A>G, rs36084323 T>C and rs7421861 A>G polymorphisms in gene position significantly decreased the risk of EGJA (OR = 0.83, 95% confidence intervals (CI) = 0.71–0.96; P = 0.015)

Summary

Introduction

A steady decline of gastric carcinoma (GC) incidence has been observed worldwide, primarily as a result of a reduction in distal GC [1]. GC is the fourth most common malignancy and is a relatively higher incidence in Eastern Asian (e.g. China, Korea and Japan). Esophagogastric junction adenocarcinoma www.impactjournals.com/oncotarget (EGJA) is one of the most rapidly increasing malignancies in North America and Europe and is thought to have different etiology compared to distal GC [2]. The increasing incidence of EGJA was identified in Eastern Asian [3, 4]. EGJA is a highly fatal form of malignancies and is a major public health problem in China. A number of studies have focused on the etiology of EGJA, it is not well understood. Some studies reported the immune system might be implicated in the etiology of EGJA [5, 6]

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