Hao Qiu1, Liang Zheng2, Weifeng Tang3, Pengfei Yin1, Feng Cheng1, Lixin Wang4. 1. Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing 210008, China. 2. Department of Cardiothoracic Surgery, The First People's Hospital of Changzhou and The Third Affiliated Hospital of Soochow University, Changzhou 213003, China. 3. Department of Cardiothoracic Surgery, Affiliated People's Hospital of Jiangsu University, Zhenjiang 212009, China. 4. Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing 210008, China. Electronic address: lxwang@seu.edu.cn.
Abstract
OBJECTIVES: Esophageal cancer is an extremely aggressive gastrointestinal malignancy, which appears to result from a complex interplay between genetic and environmental agents. The genetic loci conferring susceptibility have yet to be fully defined. Considering the role of programmed death-1 (PD-1) in immune regulation and tumor pathogenesis, we genotyped three functional single nucleotide polymorphisms (SNPs) in PD-1 in a Chinese population to explore whether these three SNPs confer susceptibility to esophageal cancer. DESIGN AND METHODS: A total of 629 new diagnosed esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this hospital-based case-control study. Genotyping was performed by the polymerase chain reaction-ligase detection reaction (PCR-LDR) method in all the subjects. RESULTS: In the recessive model, when the PD-1 rs10204525 AA/AG genotypes were used as the reference group, the GG homozygote genotype was associated with a borderline statistically decreased risk of ESCC [adjusted odds ratio (OR)=0.68, 95% confidence interval (CI)=0.45-1.03, P=0.067]. However, there were no significant associations between the other two SNPs and ESCC risk. Stratified analyses showed that a significantly decreased risk of ESCC associated with PD-1 rs10204525 A>G polymorphism was overt among male and younger patients. CONCLUSIONS: Our results demonstrate for the first time that the PD-1 rs10204525 polymorphism might contribute to susceptibility of ESCC and may therefore support the hypothesis that genetic variants, influencing T cell activity-associated gene regulation, may modify cancer risk.
OBJECTIVES:Esophageal cancer is an extremely aggressive gastrointestinal malignancy, which appears to result from a complex interplay between genetic and environmental agents. The genetic loci conferring susceptibility have yet to be fully defined. Considering the role of programmed death-1 (PD-1) in immune regulation and tumor pathogenesis, we genotyped three functional single nucleotide polymorphisms (SNPs) in PD-1 in a Chinese population to explore whether these three SNPs confer susceptibility to esophageal cancer. DESIGN AND METHODS: A total of 629 new diagnosed esophageal squamous cell carcinoma (ESCC) cases and 686 controls were recruited for this hospital-based case-control study. Genotyping was performed by the polymerase chain reaction-ligase detection reaction (PCR-LDR) method in all the subjects. RESULTS: In the recessive model, when the PD-1rs10204525 AA/AG genotypes were used as the reference group, the GG homozygote genotype was associated with a borderline statistically decreased risk of ESCC [adjusted odds ratio (OR)=0.68, 95% confidence interval (CI)=0.45-1.03, P=0.067]. However, there were no significant associations between the other two SNPs and ESCC risk. Stratified analyses showed that a significantly decreased risk of ESCC associated with PD-1rs10204525 A>G polymorphism was overt among male and younger patients. CONCLUSIONS: Our results demonstrate for the first time that the PD-1rs10204525 polymorphism might contribute to susceptibility of ESCC and may therefore support the hypothesis that genetic variants, influencing T cell activity-associated gene regulation, may modify cancer risk.
Authors: S Stremitzer; Y Sunakawa; W Zhang; D Yang; Y Ning; S Stintzing; A Sebio; S Yamauchi; S Matsusaka; R El-Khoueiry; J Stift; F Wrba; T Gruenberger; H-J Lenz Journal: Pharmacogenomics J Date: 2015-03-10 Impact factor: 3.550