Manganese Superoxide Dismutase (MnSOD Val-9Ala) Gene Polymorphism and Susceptibility to Gastric Cancer

Background: Oxidative stress caused by the generation of reactive oxygen species plays an important rolein human carcinogenesis. Manganese superoxide dismutase (MnSOD) Val-9Ala in the mitochondrial targetsequence is the best known polymorphism of this enzyme. The purpose of the current research was to assess theassociation of MnSOD Val-9Ala genotypes with the risk of gastric cancer. Materials and Methods: This casecontrolstudy covered 54 gastric cancer patients compared to 100 cancer free subjects as controls. Extractionof DNA was performed on bioptic samples and genotypes were identified with a polymerase chain reactionrestrictionfragment length polymorphism (PCR-RFLP) method. Results: The frequencies of MnSOD Ala/Ala,Ala/Val and Val/Val genotypes in healthy individuals were 24.3, 66.7 and 9%, respectively. However, in gastriccancer patients, Ala/Ala, Ala/Val and Val/Val were observed in 24.0, 48.0 and 28.0% (p=0.01). In patients thefrequency of MnSOD Val allele was higher (52%) compared to that in controls (42%). Conclusions: The resultsof this study show a positive association between MnSOD Val-9Ala gene polymorphism and risk of gastric cancerdisease in Iranian population.     

白细胞介素-12B基因多态性与胃癌遗传易感性的关系

[目的]研究白细胞介素（IL-12B）基因3’UTR（A1188C）位点多态性与江苏地区胃癌发生的关系。[方法]采用聚合酶链反应-限制性片段长度多态性（RFLP）分析法检测1045例胃癌新发病例和1100例与病例性别、年龄匹配的健康对照人群的IL-12B基因1188A／C位点多态性。[结果]IL-12B基因1188A／C位点基因多态性在正常人群和胃癌患者中的分布无显著性差异（P〉0．05）,但在饮酒的人群中,携带1188C等位基因可降低患胃癌的危险（OR=0．69,95％CI=0．47～0．99）。[结论]IL-12B基因1188A／C位点基因多态性可能与江苏地区饮酒人群胃癌的发生有关。     

Interleukin-6 Genetic Variation and Susceptibility to Gastric Cancer in an Iranian Population

Background: Despite recent decrease in the incidence of gastric cancer, it is still a common type of cancer in the north of Iran. Many evaluations have shown that polymorphisms of cytokine genes like that for interleukin 6 (IL-6), which play important roles in regulation of the immune response, can increase the risk of gastric cancer. This study examined the role of the IL-6-174 gene polymorphism in susceptibility in an Iranian population. Method: Genomic DNA was extracted from peripheral whole blood of 100 patients and 361 healthy controls. Genotyping was accomplished by the sequence-specific primer-polymerase chain reaction (SSP-PCR) method and statistical analyses were carried out using Fisher’s exact test. Frequencies of the IL-6-174 G/C genotypes were determined under co-dominant, dominant, and recessive genetic models. Results: An association between the polymorphism of IL-6 -174 G/C and susceptibility to gastric cancer was observed. The frequency of G allele was higher in patients (78%) than in controls (70.5 %) (OR=1.48, 95% CI=1.01-2.20, P=0.04). Conclusions: The high G allele and G/G genotype frequency in patients compared to control subjects suggests that the IL-6 -174 G/C polymorphism may influence the susceptibility to gastric cancer. In addition, the demographic information showed that most of the subjects were male (69.0%) that gastric cancer is related to environmental factors.     

白细胞介素-1B 基因多态性、幽门螺杆菌感染与胃癌发生的相关性

 目的 探讨湖南衡阳地区白细胞介素-1B（IL-1B）基因多态性与胃癌的关系以及幽门螺杆菌（Helicobacter pylori,HP）感染后胃癌发生的易感基因型。方法 52例胃癌患者癌旁正常胃粘膜组织和55例慢性胃炎患者胃粘膜组织,均经快速尿素酶和PCR检测HP,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析技术,进行基因型检测,并对C/C、T/T进行测序,比较各基因型在胃癌组和胃炎组中的分布差异。结果 IL-1B-31T、IL-1B-511T等位基因和IL-1B-31T/T、IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为1.97（95%CI=1.15-3.59）、2.52（95%CI=1.45-4.39）和2.71（95%CI=1.10-6.66）、3.33（95%CI=1.14-9.73）。在伴有HP感染的群体中进行比较,IL-1B-31位点各基因型未见明显差异;但IL-1B-511T等位基因和IL-1B-511T/T基因型在胃癌组的分布频率高于胃炎组（P〈0.05）,OR值分别为2.16（95%CI=1.10-4.23）和3.43（95%CI=1.01-11.62）。结论 在湖南衡阳地区IL-1B-31T/T、IL-1B-511T/T基因型与胃癌发病风险相关,在HP被感染后IL-1B-511T/T基因型可能为湖南衡阳地区胃癌易感基因型。     

A Cyclin D1 (CCND1) Gene Polymorphism Contributes to Susceptibility to Papillary Thyroid Cancer in the Turkish Population

Cyclin D1 is an important positive regulator of the G1/S phase of the cell cycle. We investigated the association between the CCND1 G870A polymorphism and susceptibility to papillary thyroid cancer in Turkish people. This study covered 102 patients with papillary thyroid cancer and 174 healthy controls. CCND1 genotypingwas determined by the PCR-RFLP method. We found that the A allele frequency was higher in the cases than in the controls (p=0.042). On stratification analysis, papillary thyroid cancer risk was significantly elevated in individuals older than 45 years with the A allele (OR=1.91, 95% CI, 1.09-3.35, p=0.024) and in females with the A allele (OR=1.73, 95% CI, 1.06-2.84, p=0.029), compared to the G allele. According to the subject age, there was an increased papillary thyroid cancer risk for the individuals older than 45 years with the AA genotype (OR=2.28, 95% CI, 1.02-5.13, p=0.046) compared to the AG+GG combined genotypes. In conclusion, it is suggested that the CCND1 G870A polymorphism may contribute to the susceptibility to papillary thyroid cancer, especially in those who were older subjects (45≤ years old) and female, in the Turkish population.     

DNA修复基因hOGG1多态与肺癌遗传易感性

背景与目的 :研究修复8_羟基鸟嘌呤的hOGG1基因Ser326Cys多态与中国人肺癌易感性的关系。 材料与方法 :采用病例_对照分子流行病学方法 ,以PCR_限制性片段多态(Restrictionfragmentlengthpolymorphism,RFLP)技术 ,对128名正常对照和124例肺癌患者hOGG1基因第326位点Ser/Cys多态性进行分析 ,并比较不同基因型与肺癌发病危险的关系。 结果: 对照组和肺癌组人群的Cys等位基因频率基本相同(37.5 %和39.9 %) ,但肺癌组的Cys/Cys基因型频率为19.4 % ,高于对照组的10.2 %。与携带Ser/Ser或Ser/Cys基因型者比较 ,携带Cys/Cys基因型个体患肺癌的危险约增加1倍(OR^ =2.12 ,95 %CI=1.03～4.39)。 结论: hOGG1基因Ser326Cys多态可能与中国人肺癌易感性相关 ,可以作为肺癌遗传易感性标志物 ,用于易感个体的预警和预防。     

Association Between the GSTP1 Codon 105 Polymorphism and Gastric Cancer Risk: an Updated Meta-analysis

Objective: The current meta-analysis was performed to address a more accurate estimation of the associationbetween glutathione S-transferase P1 (GSTP1) codon 105 polymorphism and risk of gastric cancer (GC), whichhas been widely reported with conflicting results. Methods: A comprehensive literature search was conductedto identify all the relevant studies. Fixed or random effect models were selected based on the heterogeneitytest. Publication bias was estimated using Begg’s funnel plots and Egger’s regression test. Results: A total of 20studies containing 2,821 GC cases and 6,240 controls were finally included in the analyses. Overall, no significantassociation between GSTP1 polymorphism and GC risk was observed in worldwide populations. However,subgroup analysis stratified by ethnicity showed that GSTP1 polymorphism was significantly associated withincreased risk of GC in Asians (G vs. A, OR = 1.273, 95%CI=1.011-1.605; GG vs. AA, OR=2.103, 95%CI=1.197-3.387; GG vs. AA+AG, OR =2.103, 95%CI=1.186-3.414). In contrast, no significant association was found inCaucasians in any genetic models, except for with AG vs. AA (OR=0.791, 95%CI=0.669-0.936). Furthermore, theGSTP1 polymorphism was found to be significantly associated with GC in patients with H. pylori infection andin those with a cardiac GC. Subgroup analysis stratified by Lauren’s classification and smoking status showedno significant association with any genetic model. No studies were found to significantly influence the pooledeffects in each genetic mode, and no potential publication bias was detected. Conclusions: This meta-analysissuggested that the GSTP1 polymorphism might be associated with increased risk of GC in Asians, while GSTP1heterozygote genotype seemed to be associated with reduced risk of GC. Since potential confounders could notbe ruled out completely, further studies are needed to confirm these results.     

Analysis of Polymorphism and Expression Profile of ASIC1 and IL-6 Genes in Patients with Gastric Cancer

Abstract: Gastric cancer is one of the most common upper gastrointestinal malignancies. Some Iranian provinces,such as in the northern and northwestern areas, are at a high risk, whereas the central and western provinces are ata medium and the southern regions at low risk. This study was carried out to estimate the impact of the expressionpatterns of ASIC1 and IL-6 genes and the IL-6rs-174 and ASIC1rs 75624685 polymorphisms in the pathogenesis ofgastric cancer. Materials and methods: Tetra-ARMS PCR was employed to analyze the polymorphism status of theASIC1 and IL-6 genes with 85 paraffin-embedded tissue blocks from cases and 117 normal blood samples as controls.We also investigated mRNA expression levels of these genes in 12 cases and controls using real-time PCR. Results:Our results showed a significant association between expression of ASIC1 and elevated risk of gastric cancer (p<0.001).     

MTHFR基因遗传多态与食管癌贲门癌易感性的关系

目的:探讨食管癌高发区亚甲基四氢叶酸还原酶(MTHFR)基因单核苷酸多态与食管癌、贲门癌发病风险的关系。方法:以聚合酶链反应和限制性片段长度多态方法,分析584例食管癌患者、467例贲门癌患者和540例正常对照的MTHFR基因C677T基因型及其与食管癌、贲门癌发病风险的相关性。结果:在正常对照中,MTH-FR677CC、CT、TT基因型频率分别为22.1%、43.3%和34.6%,在食管癌患者中分别为12.5%、45.0%和42.5%(P=0.000);在贲门癌患者中分别为15.8%、43.5%和40.7%(P=0.024)。多因素分析发现,携带677TT基因型和677CT基因型的个体发生食管癌的风险分别是677CC基因型的2.36倍和1.76倍,发生贲门癌的风险分别是1.34倍和1.23倍。结论:MTHFR单核苷酸多态是食管癌高发区食管癌和贲门癌的遗传易感性因素。     

Clinicopathological Factors and Gastric Cancer Prognosis in the Iranian Population: a Meta-analysis

Background: Gastric cancer is the most common cancer in the Iranian population. The aim of this study wasto determine the effect of clinicopathological factors on prognosis by meta-analysis. Materials and Methods:A literature search was conducted using MEDLINE, EMBASE and Cochrane library and extensive literaturesearch using the Persian databases until February 2011. Prospective follow up studies with multivariate analysisof overall survival of the patients with gastric cancer were included in this review. The data were analyzed byCMA.2. Publication bias are checked by funnel plot and data are shown as Forest plots. Results: From a totalof 63 articles, 14 retrospective studies which examined 5 prognostic factors and involving 10,500 patients wereincluded. Tumor size (>35mm) was the main significant factor predicting an unfavorable prognosis for the patientswith gastric cancer (RR=1.829 , p<0.001) followed by presence of distant metastases (RR=1.607 , p<0.001), poordifferentiation (RR=1.408 , p<0.001) and male sex (RR=1.194, p<0.001). Lymph node metastases (RR=1.058,p=0.698) and moderate differentiation (RR=0.836, p=0.043) were not statistically significant as prognosticfactors. Conclusions: This meta-analysis suggests that tumor size>35mm, poor differentiation, presence of distantmetastasis and male gender are strongly associated with a poor prognosis in Iranian patients with gastric cancer.     

Evaluation of Insulin Like Growth Facror-1 Genetic Polymorphism with Gastric Cancer Susceptibility and Clinicopathological Features

Gastric cancer (GC) is one of the most common malignancies in the world. It is the first cause of cancerdeaths in both sexes In Iranian population. Circulating insulin-like growth factor-one (IGF-1) levels have beenassociated for gastric cancer. IGF-1 protein has central roles involved in the regulation of epithelial cell growth,proliferation, transformation, apoptosis and metastasis. Single nucleotide polymorphism in IGF-1 regulatoryelements may lead to alter in IGF-1expression level and GC susceptibility. The aim of this study was to investigatethe influence of IGF-1 gene polymorphism (rs5742612) on risk of GC and clinicopathological features for thefirst time in Iranian population. In total, 241 subjects including 100 patients with GC and 141 healthy controlswere recruited in our study. Genotypes were analyzed using polymerase chain reaction-restriction fragmentlength polymorphism (PCR-RFLP) assay with DNA from peripheral blood. The polymorphism was statisticallyanalyzed to investigate the relationship with the risk of GC and clinicopathological properties. Logistic regressionanalysis revealed that there was no significant association between rs5742612 and the risk of GC. In addition,no significant association between genotypes and clinicopathological features was observed (p value>0.05). Thefrequencies of the CC, CT, and TT genotypes were 97%, 3%, and 0%, respectively, among the cases, and 97.9%,2.1%, and 0%, respectively, among the controls. CC genotype was more frequent in cases and controls. Thefrequencies of C and T alleles were 98.9% and 1.1% in controls and 98.5% and 1.5% in patient respectively.Our results provide the first evidence that this variant is rare in Iranian population and it may not be a powerfulgenetic predisposing biomarker for prediction GC clinicopathological features in an Iranian population.     

Lack of Effects of Single Nucleotide Polymorphisms of the DNA Methyltransferase 1 Gene on Gastric Cancer in Iranian Patients: A Case Control Study

Background: Gastric cancer is one of the most common malignant tumors in Iran. Hypomethylation and/orhypermethylation of DNA has been described in gastric cancer and is presumed to be an early event incarcinogeneisis. Objective: We therefore hypothesized that single nucleotide polymorphisms of the DNMT1gene may be associated with the genetic susceptibility to gastric cancer. Methods: Totals of 200 patients and 200controls, both of Iranian origin, were studied. Three polymorphisms were genotyped by PCR-RFLP and allelefrequencies and genotypes were compared between the cases and controls. Odds ratios were calculated and theinteractions between the polymorphisms, age and sex were examined. Results : There were no significantassociations between the DNMT1 polymorphisms and gastric cancer. Conclusion: We could not show anyassociation between DNMT1 polymorphisms and gastric cancer. Larger sets of polymorphisms and samplesizes are required for future testing of possible associations.     

SLCO1B1基因多态性与伊立替康所致不良反应的关系

伊立替康(CPT-11)是一种临床应用广泛的抗肿瘤药物,但其可能发生的严重不良反应却常常影响它的临床使用.有关报道称,特异性分布于肝细胞基底膜外侧的有机阴离子转运蛋白1B1(OATP1B1)可显著影响CPT-11及其活性产物SN-38的血药浓度,进而影响它的不良反应.文章就负责编码OATP1B1的编码基因SLCO1B1的基因多态性与CPT-11所致不良反应的关系作一综述.     

Polymorphism in GSTM1, GSTT1, and GSTP1 and Susceptibility to Lung Cancer in a Japanese Population

Polymorphisms in glutathione S-transferases (GSTs) may predispose to lung cancer through deficient detoxification ‍of carcinogenic or toxic constituents in cigarette smoke, although previous results have been conflicting. Three GST ‍polymorphisms (GSTM1, GSTT1 and GSTP1) were determined among 86 male patients with lung carcinomas and ‍88 healthy male subjects. We found no significant increase in the risk of lung cancer for any genotypes for the nulled ‍GSTM1 [odds ratio (OR)=2.0; 95% confidence interval (95% CI)= 0.8-5.3], the nulled GSTT1 (OR=2.0; 95% CI=0.8- ‍5.1) or the mutated (the presence of a Val-105 allele) GSTP1 (OR=0.96; 95% CI=0.4-5.5). The GST polymorphisms ‍alone may thus not be associated with susceptibility to lung carcinogenesis in male Japanese. However, individuals ‍with a concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR=2.7; 95% CI=1.0-7.4) when ‍compared with those having at least one of these genes. No other combinations were associated with lung cancer ‍risk. These results suggest that there may be carcinogenic intermediates in cigarette smoke that are substrates for ‍both GSTM1 and GSTT1 enzymes and that lung cancer risk is increased for individuals who are doubly deleted at ‍GSTM1 and GSTT1 gene loci. Additional large studies are needed to confirm this observation.     

IL-1β基因多态性、幽门螺旋杆菌感染及其交互作用与新疆汉族胃癌发生的关系

目的探讨IL-1β基因多态性、幽门螺旋杆菌(Helicobacter pylori,HP)感染及其交互作用与新疆汉族胃癌发生的关系。方法采用Snapshot技术分析229例胃癌患者和作为对照的256例非胃癌患者IL-1β基因rs1143633、rs3136558和rs1143630位点基因型的分布;采用幽门螺旋杆菌IgG抗体检测试剂盒检测研究对象Hp感染率。结果IL-1β基因rs3136558位点多态性、Hp感染与新疆汉族胃癌的发病有关;Hp感染与基因之间的交互作用表明,在汉族人群中,Hp感染阳性,同时携带IL-1β基因 rs3136558 TT基因型个体发生胃癌的危险性是Hp感染阴性并携带IL-1β基因 rs3136558 CT+CC基因型个体的2.25倍 (95% CI：1.37~3.69)。结论Hp感染和IL-1β基因多态之间存在着交互作用,共同促进胃癌的发生。     

IL-17A Levels in the Sera of Patients with Gastric Cancer Show Limited Elevation

Background: Inflammation plays a major role in the development and progression of gastric and othergastrointestinal tumors. The IL-17 family of cytokines has been under investigation as targets of immunotherapy.Materials and Methods: We investigated the levels of IL-17A inflammatory cytokine in the sera of 57 patients withgastric cancer (GC) and 90 healthy age/sex matched controls using ELISA methods. Results: In only 5 (8.8%) ofthe patients’ sera was IL-17A detectable. No IL-17A was apparent in the sera of healthy controls. The maximumconcentration of IL-17A in patients was 7.004 pg/ml. Vascular and lymphatic invasions were only seen in oneof the 5 positive cases. Although all of them were in the age group >60 years, no correlation was seen betweenage and IL-17A level. These results are somewhat different from our findings for colorectal cancer (CRC) in thesame population. Conclusions: It is possible that the inflammopathology of CRC and GC are rather different,at least in Fars, a southern province of Iran.     

Lack of Association of the MDR1 C3435T Polymorphism with Susceptibility to Gastric Cancer and Peptic Ulcer: a Systemic Review and Meta-analysis

Background: The multidrug resistance 1 gene (MDR1) C3435T polymorphism has been demonstrated toinfluence the P-glycoprotein (P-gp) activity level which is related to inflammation and carcinogenesis. Thismeta-analysis was performed to estimate the association between the MDR1 C3435T polymorphism and therisk of gastric cancer (GC) and peptic ulcer (PU). Materials and Methods: A literature search was conductedwith PubMed, Embase and the Cochrane library up to November 2013. Odds ratios (ORs) with 95% confidenceintervals (CIs) were used to assess the strength of association. Data were analyzed using Review Manager (Version5.2), and Stata package (version 12.0) for estimation of publication bias. Results: Six case-control studies wereincluded, of which five were for GC and two for PU. Overall, no evidence was found for any association betweenthe MDR1 C3435T polymorphism and the susceptibility to GC and PU. In the stratified analysis by H. pyloriinfection status, stage and histology classification of GC, and PU type, there was still no significant associationbetween them. Conclusions: This meta-analysis suggested that the MDR1 C3435T polymorphism is not associatedwith susceptibility to GC and PU. Large and well-designed studies are warranted to validate our findings.     

Interleukin-12 and Interleukin-6 Gene Polymorphisms and Risk of Bladder Cancer in the Iranian Population

Interleukin-12 (IL-12) as an antitumor and interleukin-6 (IL-6) as an inflammatory cytokine, areimmunomodulatory products that play important roles in responses in cancers and inflammation. We testedthe association between two polymorphisms of IL-12(1188A>C; rs3212227) and IL-6 (-174 C>G) and the riskof bladder cancer in 261 patients and 251 healthy individuals. We also investigated the possible association ofthese SNPs in patients with high-risk jobs and smoking habits with the incidence of bladder cancer. The genotypedistributions of IL-6 (-174 C/G) genotype were similar between the cases and the control groups; however, amongpatients with smoking habits, the association between IL-6 gene polymorphism and incidence of bladder cancerwas significant. After a control adjustment for age and sex, the following results were recorded: CC genotype(OR= 2.11, 95%CI=1.56-2.87, p=0.007), GC genotype (OR=2.18, 95%CI=1.16-4.12, p=0.014) and GC+ CC(OR=2.6, 95%CI=1.43-4.47, p=0.011). A significant risk of bladder cancer was observed for the heterozygousgenotype (AC) of IL-12 (OR=1.47, 95%CI=1.01-2.14, p=0.045) in all cases, and among smokers (AC) (OR=3.13,95%CI=1.82-5.37, p=0.00014), combined AC+CC (OR=3.05, 95%CI=1.8-5.18, p=0.000015). Moreover amonghigh risk job patients, there was more than a 3-fold increased risk of cancer in the carriers of IL-12 betaheterozygous (OR=3.7, 95%CI=2.04-6.57, p=0.000056) and combined AC+CC(OR=3.29, 95%CI=1.58-5.86,p=0.00002) genotypes as compared with the AA genotype with low-risk jobs. As a conclusion, this study suggeststhat IL-12(3’UTR A>C) and IL-6 (-174 C>G) genotypes are significantly associated with an increased risk ofbladder cancer in the Iranian population with smoking habits and/or performing high-risk jobs.