Association between interleukin gene polymorphisms and susceptibility to gastric cancer in the Qinghai population

ObjectiveTo investigate the associations between interleukin (IL) gene polymorphisms and susceptibility to gastric cancer in the Qinghai population, China.MethodsPatients with gastric cancer and cancer-free controls were enrolled into the study from Qinghai Provincial People’s Hospital between September 2016 and September 2018. Single nucleotide polymorphisms (SNPs) were genotyped with the Sequenom MassARRAY® SNP genotype system. The Hardy–Weinberg equilibrium in allele and genotype frequencies, and general characteristics between patients with gastric cancer and cancer-free controls, were evaluated using χ²-test. Potential associations between interleukin gene variants and the risk of gastric cancer were analysed by logistic regression.ResultsAmong eight candidate SNPs, the allele and genotype frequency distribution of IL-1B rs1143634 polymorphism was significantly different between patients with gastric cancer (n = 190) and cancer-free controls (n = 186). The IL-1B rs1143634 GA genotype and IL-1B rs1143634 GA + AA genotype were associated with a reduced risk of gastric cancer, however, the remaining SNPs were not statistically associated with gastric cancer risk in the Qinghai population.ConclusionThe IL-1B rs1143634 polymorphism might be associated with a decreased risk of gastric cancer, and may be a protective factor against gastric cancer.     

Influence of ADRB1, ADRB2, and COMT Genetic Polymorphisms on Postoperative Outcomes of Patients Undergoing Cardiac Valve Surgery

PurposeThe aim of this study is to prospectively investigate the influence of ADRB and COMT gene polymorphisms on postoperative outcomes of patients undergoing cardiac surgery.MethodsThis prospective cohort study included 223 patients undergoing elective cardiac valve surgery using cardiopulmonary bypass. Demographic information, intraoperative data, postoperative data, and blood samples were collected. Patients were genotyped for single-nucleotide polymorphisms (SNPs) of ADRB1 rs1801253, ADRB2 rs1042713, and COMT rs4680. Major adverse cardiovascular and cerebrovascular events (MACCEs) were used as the primary outcome to evaluate the postoperative prognosis of patients. Secondary outcomes included the duration of mechanical ventilatory support, intensive care unit stay, postoperative hospital stay, and postoperative need of inotropic or vasoactive agents.FindingsThe overall incidence of MACCEs was 15.2%. Among 3 SNP loci, only different genotyped carriers of ADRB2 rs1042713 had statistically significant differences in the incidence of MACCEs (P = 0.005), especially for acute kidney injury (P = 0.023). The proportions of postoperative norepinephrine demand of patients carrying the AA genotype of ADRB2 rs1042713 (P = 0.016) and the AG genotype of COMT rs4680 (P = 0.018) were low. The duration of mechanical ventilatory support (P = 0.034) and postoperative hospital stay (P = 0.045) of patients carrying the AG genotype of COMT rs4680 was shortest. After multiple logistic regression analysis, we found that the G allele carriers of ADRB2 rs1042713 had a higher risk of MACCEs (AG vs AA genotype: odds ratio [OR] = 4.348; 95% CI, 1.529–12.359, P = 0.006; GG vs AA genotype: OR = 3.722; 95% CI, 1.060–13.071; P = 0.040), in particular with acute kidney injury (AG vs AA genotype: OR = 5.273; 95% CI, 1.093–25.451; P = 0.038; GG vs AA genotype: OR = 7.533; 95% CI, 1.275–44.522; P = 0.026). There was no SNP-SNP interaction found among the 3 SNPs with multifactor dimensionality reduction analysis.ImplicationThe ADRB2 rs1042713 polymorphism might be related to prognosis of patients undergoing cardiac surgery. Patients carrying the G allele of ADRB2 rs1042713 had a higher risk of developing MACCEs, especially acute kidney injury. chictr.org.com identifier: ChiCTR1800015105.     

TLR4基因多态性与重症社区获得性肺炎易感性和预后的关联

目的 探讨Toll样受体4(toll-like-receptor4,TLR4)基因单核苷酸多态性(single nucleotide polymorphism,SNP)与中国汉族人群重症社区获得性肺炎(severe community-acquired pneumonia,SCAP)的易感性和预后的相关性.方法 收集2005年5月至2008年4月复旦大学附属中山医院急诊科收治的360例社区获得性肺炎(conununity-acquired pneumonia,CAP)患者进行前瞻性研究.排除既往患有自身免疫性疾病、正在应用免疫抑制剂、AIDS和肿瘤患者.本研究获得复旦大学附属中山医院伦理委员会同意.根据患者的病情程度分为SCAP组和NSCAP组,每组各180例.根据患者30 d内是否存活,分为存活组和死亡组,存活组300例,死亡组60例.利用Hapmap中国人群数据库选择SNPs和标签SNPs(TagSNPs),利用Primer 3软件设计引物;采用DNA抽提试剂盒提取外周血DNA,PER-直接测序法进行SNPs分型.基因型频率和等位基因频率在各组之间的比较采用χ2检验.结果 TLR4基因3个TagSNPs(rs2149356,rs11536879,rs1927907)等位基因频率分布在研究样本中符合Hardy-Weinberg平衡.TagSNPs等位基因频率和基因型频率在SCAP组和非重症肺炎(non-SCAP,NSCAP)组相比,差异无统计学意义;存活组和死亡组相比,差异无统计学意义(P＞0.05);研究发现由rs2149356和rs11536879组成的3种单倍型(GA,TA,TG)频率在SCAP组和NSCAP组差异无统计学意义,在死亡组和存活组中差异无统计学意义(P＞0.05).结论 TLR4基因多态性与中国汉族人群SCAP的易感性和预后无相关性.     

Association study of genetic variants at TTC32‐WDR35 gene cluster with coronary artery disease in Chinese Han population

BackgroundTTC32‐WDR35 gene cluster has been genome‐wide significantly associated with coronary artery disease (CAD). However, the common variants in this region contributing to CAD risk remain elusive.MethodsWe performed a case‐control study enrolling 935 CAD cases and 935 age‐sex‐frequency‐matched controls from unrelated southwest Chinese Han population. Five variants were determined by TaqMan assay.ResultsThis study indicated that rs721932 CG genotype was associated with CAD risk (OR = 0.68, 95% CI: 0.54‐0.86; P = .001). Stratified analysis showed that the risk associated with rs12617744 AA genotype was robust in male (OR = 0.62, 95% CI: 0.42‐0.93, P = .02). The gene dosage of the risk allele at rs12617744 showed a significant association with left circumflex artery disease (P = .027) and the number of vascular lesions in patients (P = .034). Moreover, the gene dosage of rs721932 risk allele was associated with vascular lesion numbers (P = .048) and the progression of CAD (P = .028). Compared with carriers of major alleles, the AA genotype of rs12617744 and GG genotype of rs721932 were both associated with plasma HDL level (P = .009 and 0.004, respectively). Expression quantitative trait locus (eQTL) results showed significantly different TTC32 expression of subjects as a function of SNPs (rs2278528, rs7594214, and rs721932) genotype in the artery. Besides, FPRP analysis did support the strong links between polymorphisms and CAD risk.ConclusionsSNP rs721932 at TTC32‐WDR35 Gene Cluster was associated with CAD risk, and rs12617744 was associated with the risk of CAD among males. Both SNPs may contribute to the regulation of plasma HDL levels and possibly to the severity of CAD in Chinese Han population.     

Relationships of interleukin-17 polymorphisms with recurrent aphthous ulcer risk in a Han Chinese population

ObjectiveInterleukin (IL)-17 is a multifunctional cytokine with important roles in inflammatory and autoimmune diseases. This case–control study explored the relationships of IL-17A rs2275913 and IL-17F rs763780 single-nucleotide polymorphisms (SNPs) with recurrent aphthous ulcer (RAU) morbidity and severity.MethodsIL-17A rs2275913 and IL-17F rs763780 SNPs were measured in 125 patients with RAU and 116 healthy control participants. The genotype distributions, disease risks, and relationships with RAU severity were analyzed.ResultsRAU risk was associated with rs2275913 after adjustment for age, body mass index, sex, smoking status, and drinking status (AA vs. GG: odds ratio [OR], 2.759; 95% confidence interval [CI], 1.381–5.512; A allele vs. G allele: OR, 1.783; 95% CI, 1.242–2.560). TC and CC genotypes in rs763780, and the corresponding C allele, demonstrated greater prevalence among patients with RAU, compared with the TT genotype (TC vs. TT, OR: 1.895; 95% CI: 1.088–3.301; CC vs. TT, OR: 4.080, 95% CI: 1.079–15.425; C allele vs. T allele, OR: 1.969, 95% CI: 1.257–3.083). Serum IL-17 concentrations were also higher in patients with RAU than in control participants. These concentrations were associated with IL-17 polymorphisms.ConclusionsIL-17 polymorphisms might be associated with greater risk of RAU pathogenesis.     

The CDKN2A polymorphisms and the susceptibility of HBV‐related gestational diabetes mellitus

Background

Single‐nucleotide polymorphisms (SNPs) were discovered in HBV‐related gestational diabetes mellitus, but it still unclear whether these SNPs are associated with the susceptibility of HBV‐related gestational diabetes mellitus.

Methods

The investigation of the association between CDKN2A polymorphisms and occurrence of HBV‐related gestational diabetes mellitus (GDM) in Chinese was assessed in the case‐control study. A total of 480 pregnant patients with HBV and 530 pregnant controls were consecutively recruited from January 2015 to December 2016. Polymerase chain reaction‐restriction fragment length polymorphisms (PCR‐RFLP) method was applied to measure genotyping for the detection of CDKN2A.

Results

The significant differences in the frequency of CDKN2A genotype distributions, rs10811661 and rs564398, were found by Chi‐square test. Using conditional logistic analysis, individuals carrying the CDKN2A rs10811661 TC and TT genotypes and CDKN2A rs564398 AA and AG genotypes were related to a greater risk of HBV‐related GDM compared with the genotype.

Conclusions

In conclusion, the CDKN2A rs10811661 and rs564398 polymorphisms showed association with a greater risk of HBV‐related GDM in a Chinese population.

     

Association of FAM13A polymorphisms with COPD and COPD-related phenotypes in Han Chinese

ObjectivesGenome-wide association studies (GWAS) and integrative genomics approaches have demonstrated significant associations between chronic obstructive pulmonary disease (COPD) and FAM13A polymorphisms in non-Asian populations. The aim of this study was to investigate whether FAM13A polymorphisms would be associated with COPD susceptibility and COPD-related phenotypes in a Chinese Han population.MethodsSeven single nucleotide polymorphisms (SNPs) (rs7671167, rs10007590, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) in FAM13A gene were genotyped in a case–control study (680 COPD patients and 687 controls). Allele frequencies and genotype distributions were compared between patients and controls. To estimate the strength of association, odds ratios (OR) (with 95% CI) were calculated and potential confounding variables were tested by using logistic regression analysis.ResultsStatistical analysis revealed that SNP rs7671167 was associated with COPD in former smokers with adjusted P-value of 0.026. Five SNPs (rs7671167, rs2869966, rs2869967, rs2045517, and rs6830970) were associated with FEV1/FVC ratio in the entire cohort and rs6830970 was associated with FEV1/FVC ratio in COPD cases (P range 0.003–0.034). Borderline associations with FEV1/FVC ratio were found for rs2869966, rs2869967 and rs2045517 among cases (P = 0.05). Six SNPs (rs7671167, rs2869966, rs2869967, rs2045517, rs1903003, rs6830970) showed strong linkage disequilibrium (r² ≥ 0.9). Four major haplotypes were observed but showed no significant difference between case and control groups (P = 0.2356, 0.1273, 0.6266 and 0.3006 respectively).ConclusionsThe current study suggests that the FAM13A locus might be a contributor to COPD susceptibility in Chinese Han population.     

Polymorphism at the mucin-like protocadherin gene influences susceptibility to gallstone disease

BackgroundGallstone disease (GSD) is a common disease that can be caused by environmental influences, common genetic factors and their interactions. Mucin glycoproteins may be one important factor for GSD. We conducted a case–control study to investigate the relationship between the mucin-like protocadherin (MUPCDH) gene polymorphisms and GSD.MethodsThe study included 452 GSD cases and 491 healthy controls who had no evidence of gallstones by ultrasound examination. Two common tagging single nucleotide polymorphism (SNP) rs3758650 and rs7932167, and four non-synonymous SNPs rs34362213, rs2740375, rs7108757 and rs2740379 were genotyped. The genetic effects were evaluated using the multivariate regression model.ResultsThe genotypes of these SNPs were all in Hardy–Weinberg equilibrium. Three non-synonymous SNPs (rs34362213, rs7108757 and rs2740379) were monomorphic. The single SNP analysis showed two SNPs (rs7932167 and rs2740375) were not associated with GSD and only SNP rs3758650 had the association of the presence of GSD with an odds ratio (OR) of 1.59 (adjusted P = 0.013) for the AG genotype and 5.82 (adjusted P = 0.007) for the AA genotype when compared with the reference GG genotype. The haplotype analysis of the three polymorphic SNPs showed GCA was significant for GSD (adjusted p = 0.001) with an odds ratio (OR) of 1.41 when compared to other haplotypes.ConclusionsThe MUPCDH genetic polymorphism rs3758650 was considered a genetic marker to predict symptomatic GSD subjects. It may be of importance for GSD patients with the risk SNPs to be frequently checked because they may develop symptomatic GSD.     

A polymorphism in the 3′-untranslated region of the matrix metallopeptidase 9 gene is associated with susceptibility to idiopathic calcium nephrolithiasis in the Chinese population

ObjectiveTo investigate whether single nucleotide polymorphisms (SNPs) in the 3′ untranslated region (UTR) of the matrix metallopeptidase 9 gene (MMP9) are associated with susceptibility to calcium oxalate stones.MethodsA total of 428 patients with kidney stone disease (KSD) and 450 control individuals were enrolled. Three MMP9 SNPs (rs20544, rs9509, and rs1056628) were genotyped, and MMP9 mRNA and protein expression was determined in patients and controls. The dual luciferase reporter gene assay was conducted by transfecting HEK293 cells with miR-491-5p mimics and plasmids containing MMP9 with rs1056628 AA/CC genotypes.ResultsThe rs1056628 CC genotype was significantly increased in KSD patients compared with controls (CC vs AA: odds ratio [OR] = 2.279, 95% confidence interval [CI] = 1.048–4.956). The rs1056628 C allele frequency was higher in KSD patients than controls. The increased KSD risks associated with rs1056628 were more evident in individuals aged <30 years (OR = 3.504, 95% CI = 1.102–11.139) and men (OR = 2.522, 95% CI = 1.004–6.334). mRNA and protein levels of MMP9 were significantly higher in KSD patients with the CC genotype than in those with the AA genotype.ConclusionThis study demonstrates that MMP9 SNP rs1056628 is associated with a significant KSD risk in Chinese Han individuals.     

A genetic polymorphism of IL17F rs763780 associated with anti-E production in the Han Chinese population

ObjectiveThis study aimed to investigate the association among 4 single nucleotide polymorphisms (SNPs) in the genes TLR3, IL17F, ERAP1 and ERAP2 with anti-E alloantibody production.BackgroundAnti-E alloantibodies can lead to clinically significant delayed hemolytic transfusion reactions (DHTRs) and hemolytic disease of the newborn (HDN). Some individuals produce anti-E alloantibodies post- transfusion. The mechanisms controlling this process is poorly understood.MethodsNinety-five patients with anti-E alloantibodies were enrolled, and samples from 186 healthy donors were used as controls. Four SNPs in the immune-related genes (TLR3, IL17F, ERAP1 and ERAP2) were selected. SNPs were analyzed by polymerase chain reactions (PCR) and TaqMan assays. Allele and genotype frequencies were compared using Pearson's chi-square test.ResultsThe C allele and CC + CT genotypes of rs763780 in the IL17F gene were overrepresented in the E- alloimmunized patient group (14.2 % vs. 5.1 %, P < 0.001; 23.2 % vs. 9.7 %; P = 0.004). Individuals with CC + CT genotypes of rs763780 had a higher risk of E-alloimmunization. (OR, 2.81; 95 % CI, 1.42–5.56). No significant difference was observed among the other 3 SNPs.ConclusionsSNP rs763780 in the IL17F gene was associated with E-alloimmunization in a sample of the Han Chinese population, with the allele C as a risk allele.     

Impact of YTHDF1 gene polymorphisms on Wilms tumor susceptibility: A five‐center case‐control study

BackgroundWilms tumor is the most frequent renal malignancy in children. YTHDF1 is associated with the development of several kinds of cancers, yet whether common variants of the YTHDF1 gene influence Wilms tumor risk is unknown. We present, here, a hospital‐based case‐control study specifically designed to investigate the role of YTHDF1 genetic variants on Wilms tumor.MethodsWe successfully genotyped samples of 408 Wilms tumor cases and 1198 controls which were collected from five hospitals across China. The unconditional logistic regression was adopted to analyze the contributions of YTHDF1 gene single nucleotide polymorphisms (SNPs) to the risk of Wilms tumor. The odds ratio (OR) and 95% confidence interval (CI) were generated to evaluate the conferring risk of YTHDF1 gene SNPs (rs6011668 C>T, rs6090311 A>G).ResultsNeither of the two SNPs could contribute to the risk of Wilms tumor. A negative association was also detected in the combined effects of protective genotypes on Wilms tumor risk. The stratification analysis revealed that compared with those with CC genotype, rs6011668 CT/TT genotype was associated with increased Wilms tumor risk in those ≤18 months (OR = 1.54, 95% CI = 1.02–2.30, p = 0.038), and with decreased Wilms tumor risk in those >18 months (OR = 0.70, 95% CI = 0.50–0.97, p = 0.034).ConclusionOur present work sheds some light on the potential role of YTHDF1 gene polymorphisms on Wilms tumor risk.     

Association between genetic polymorphisms of the NPHS1 gene and membranous glomerulonephritis in the Taiwanese population

BackgroundMembranous glomerulonephritis (MGN) is one of the most common causes of nephrotic syndrome in adults. NPHS1 encoding nephrin is a transmembrane protein of the immunoglobulin family. We clarified the relationship between NPHS1 gene polymorphisms and the susceptibility or progression of MGN.MethodsWe recruited a cohort of 132 biopsy-diagnosed MGN patients and 257 healthy subjects. Genotyping of three SNPs (rs401824, rs437168 and rs3814995) at chromosome positions 41034749 (5′UTR), 41026259(exon17) and 41034052 (exon 3) was performed using a Taqman SNP genotyping assay.ResultsThere was a significant difference in genotype frequency distribution of rs437168 polymorphism between MGN patients and controls. The results also showed that the frequency of the G allele was significantly higher in the patient group. Among the polymorphisms rs437168, rs401824 and rs3814995, no significant haplotype was shown in MGN patients. A stratified analysis revealed that a high disease progression in the AA genotype of rs401824 and GG genotype of rs437168 patients were associated with a low rate of remission.ConclusionsThe presence of the different genotypes of NPHS1 was associated with susceptibility of MGN and the remission of proteinuria during disease progression after the therapy.     

Alpha-fetoprotein gene polymorphisms and risk of HCC and cirrhosis

BackgroundElevated level of alpha fetoprotein (AFP) is found in approximately 60% of hepatocellular carcinoma (HCC) cases. Other liver diseases including cirrhosis and chronic hepatitis are related with an increased level of AFP. The regulation of AFP gene expression has been relatively less studied although the gene has been suggested to play a role in HCC development. This study aimed at identifying genetic variations in AFP that might be associated with the presence of HCC and cirrhosis among ethnic Indonesians.MethodsDirect DNA sequencing was carried out to sequence AFP promoter, exons, and 3′ untranslated region (UTR) in DNA samples isolated from 119 HCC, 119 cirrhosis and 105 control subjects. For each sample serum AFP level was determined and association studies with single nucleotide polymorphisms (SNPs) and haplotypes were performed.ResultsIn this study we identified 47 SNPs in the AFP gene. Statistically significant associations with HCC and cirrhosis were detected for six individual SNPs in the AFP promoter, AFP intron 1 and intron 2 (rs6834059, rs3796678, rs3796677, rs3796676, rs28532518 and rs4646038). Furthermore, we identified two SNPs in AFP intron 7 and 3′UTR, rs2298839 and rs10020432, which are associated with increased risk of cirrhosis.ConclusionGenetic variants in the AFP gene may be associated with HCC and cirrhosis risk for ethnic Indonesians.     

Association between SNPs in pre-miRNA and risk of chronic obstructive pulmonary disease

ObjectivesChronic obstructive pulmonary disease (COPD) is characterized by irreversible airway obstruction and persistent chronic airway inflammation and is influenced by genetic and environmental factors. This study aimed to explore the genetic aspect of its initial occurrence.Design and methodsWe conducted a case–control study of 432 COPD patients and 511 control subjects frequency-matched in age and gender distribution. We genotyped three single nucleotide polymorphisms (SNPs) in pre-miRNAs using a PCR-RFLP assay and evaluated their relevance to COPD susceptibility.ResultsWe found that the TT genotype and T allele of miR-196a2 rs11614913 were significantly associated with a decreased risk for COPD, compared with the CC genotype and C allele. Similarly, the GG genotype and G allele of miR-499 rs3746444 were associated with a decreased risk for COPD, compared with the AA genotype and A allele.ConclusionsThese findings suggest that both rs11614913 and rs3746444 may be involved in susceptibility to COPD.     

Association of ALOX5AP with ischemic stroke in eastern Chinese

BACKGROUND:

5-lipoxygenase protein (ALOX5AP) has been recognized as a susceptibility gene for stroke and coronary artery diseases. The present study was to explore the role of this gene in the eastern Chinese patients with ischemic stroke.

METHODS:

Using a case-control design, we studied 658 patients with ischemic stroke and 704 unrelated population-based controls who were age- and sex-matched. The 658 patients were classified by the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Two single-nucleotide polymorphisms (SNPs) covering ALOX5AP were genotyped.

RESULTS:

The genotype frequencies of TG of the SNPs rs17222919 located in the promoter of the ALOX5AP gene were significantly higher in patients with ischemic stroke than in controls (OR^*=1.34, 95%CI^*=1.02-1.75), especially in patients with ischemic stroke caused by small-artery occlusion (SAO) (OR^*=1.40, 95%CI^*=1.02-1.93). Meanwhile, the genotype frequencies of TG and TG/GG were higher in female patients than in the controls. After specification, the genotype frequencies of TG and TG/GG were higher in the patients than in controls with hypertension. The genotype frequencies of AG and AG/GG of the SNPs rs9579646 located in the intron of the ALOX5AP gene were higher in the controls than in the patients. After specification, the genotype frequencies of TG were higher in the controls than patients without hypertension.

CONCLUSION:

The present study suggests that sequence variants in the ALOX5AP gene are significantly associated with ischemic stroke.KEY WORDS: 5-lipoxygenase activating protein (ALOX5AP), Leukotrienes (LTs), Trial of Org 10172 in Acute Stroke Treatment (TOAST), Single nucleotide polymorphisms (SNPs), Ischemic stroke     

RAD51 gene is associated with advanced age-related macular degeneration in Chinese population

ObjectivesThis study aims to investigate whether variations in RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 are associated with advanced forms of age-related macular degeneration (AMD) in Chinese population.Design and methodsA total of 119 Chinese patients with AMD and 99 control individuals were recruited. Genomic DNA was extracted from peripheral blood leukocytes. Seven single nucleotide polymorphisms (SNPs) from CFH, HTRA1, RAD51, B3GALTL, TNFRSF10A and REST-C4ORF14-POLR2B-IGFBP7 were genotyped by polymerase chain reaction (PCR) followed by allele-specific restriction enzyme digestion or SNaPshot.ResultsRs10483810 in RAD51 was significantly associated with advanced AMD (P = 0.045). Compared with the wild-type genotype GG, the odds ratio for the risk of advanced AMD was 4.92 (95% confidence interval: 1.04–23.36) for the heterozygous TG genotype. Moreover, the GT genotype at rs10483810 confers significantly increased risk of bilateral AMD compared to unilateral AMD (OR = 12.04, 95% CI: 2.50–57.69, P = 0.002). Rs13278062 in TNFRSF10A, rs1713985 in REST-C4ORF14-POLR2B-IGFBP7 and rs9542236 in B3GALTL were not found to be associated with AMD (all P > 0.05).ConclusionOur data suggested that the risk allele T of rs10483810 in RAD51 gene is associated with an increased risk of advanced AMD, especially bilateral AMD, in Chinese population.     

Programmed death-1 (PD-1) polymorphisms in Chinese patients with esophageal cancer

ObjectivesEsophageal 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 methodsA 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.ResultsIn 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.ConclusionsOur 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.