XPC Lys939Gln polymorphism,smoking and risk of sporadic colorectal cancer among Malaysians

AIM: To investigate the risk association of xeroderma pigmentosum group C (XPC ) Lys939Gln polymorphism alone and in combination with cigarette smoking on colorectal cancer (CRC) predisposition. METHODS: Peripheral blood samples of 510 study subjects (255 CRC patients, 255 controls)were collected. DNA was extracted and genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism. The association between polymorphic genotype and CRC predisposition was determined using the OR and 95%CI. RESULTS: The frequency of the homozygous variant (Gln/Gln) genotype was significantly higher in cases compared with controls (16.0% vs 10.2%, P = 0.049). The Gln/Gln genotype of XPC showed a significantly higher association with the risk of CRC (OR = 1.884; 95%CI: 1.082-3.277; P = 0.025). In the case of allele frequencies, variant allele C was associated with a significantly increased risk of CRC (OR = 1.375; 95%CI: 1.050-1.802; P = 0.020). Moreover, the risk was markedly higher for those who were carriers of the Gln/Gln variant genotype and were also cigarette smokers (OR = 3.409; 95%CI: 1.061-10.949; P = 0.032). CONCLUSION: The XPC Gln/Gln genotype alone and in combination with smoking increases the risk of CRC among Malaysians.     

Genetic association of apolipoprotein E polymorphisms with inflammatory bowel disease

AIM:To study the association of apolipoprotein E(APOE) polymorphisms with the susceptibility ofinflammatory bowel disease(IBD) in Saudi patients.METHODS:APOE genotyping was performed to evaluate the allele and genotype frequencies in 378 Saudi subjects including IBD patients with ulcerative colitis(n = 84) or Crohn's disease(n = 94) and matched controls(n = 200) using polymerase chain reaction and reverse-hybridization techniques.RESULTS:The frequencies of the APOE ε2 allele and ε2/ε3 and ε2/ε4 genotypes were significantly higher in IBD patients than in controls(P 0.05),suggesting that the ε2 allele and its heterozygous genotypes may increase the susceptibility to IBD.On the contrary,the frequencies of the ε3 allele and ε3/ε3 genotype were lower in IBD patients as compared to controls,suggesting a protective effect of APOE ε3 for IBD.The prevalence of the ε4 allele was also higher in the patient group compared to controls,suggesting that the ε4 allele may also increase the risk of IBD.Our results also indicated that the APOE ε4 allele was associated with an early age of IBD onset.No effect of gender or type of IBD(familial or sporadic) on the frequency distribution of APOE alleles and genotypes was noticed in this study.CONCLUSION:APOE polymorphism is associated with risk of developing IBD and early age of onset in Saudi patients,though further studies with a large-size population are warranted.     

Association between polymorphisms of APE1 and OGG1 and risk of colorectal cancer in Taiwan

AIM: To evaluate the effects of OGG1(Ser326Cys, 11657A/G, and Arg154His) and APE1(Asp148Glu, and T-656G) polymorphisms on colorectal cancer(CRC) risk.METHODS: We enrolled 727 cases newly diagnosed with colorectal adenocarcinoma and 736 age- and sex-matched healthy controls from a medical center in Taiwan. Genomic DNA isolated from the buffy coat was used for genotyping through polymerase chain reaction. Unconditional logistic regressions were used for calculating ORs and 95%CIs to determine the association between the genetic polymorphisms and CRC risk. Haplotype frequencies were estimated using PHASE software. Moreover, stratification analyses onthe basis of sex, age at diagnosis, and tumor subsite and stage were performed.RESULTS: The CRC risk was higher in patients with the OGG1 326Ser/Cys + Cys/Cys genotype(OR = 1.38, 95%CI: 1.03-1.85, P = 0.030), particularly high in patients with stage Ⅲ + Ⅳ cancer(OR = 1.48, 95%CI: 1.03-2.13) compared with patients with the Ser/Ser genotype. In addition, OGG1 11657 G allele carriers had a 41% reduced CRC risk among stage 0-Ⅱ patients(OR = 0.59, 95%CI: 0.35-0.98). The CRC risk was significantly higher among females with the APE1 Glu allele(OR = 1.41, 95%CI: 1.02-1.96). The APE1 148Glu/-656 G haplotype was also associated with a significant CRC risk in females(OR = 1.36, 95%CI: 1.03-1.78).CONCLUSION: OGG1 and APE1 polymorphisms are associated with stage- and sex-specific risk of CRC in the Taiwanese population.     

The potential association of tumor necrosis factor-βeta (252 G/A) cytokine gene polymorphism with immune thrombocytopenic purpura among Egyptian children

Objectives: The main objective of this study was to study tumor necrosis factor beta (TNFB)?+?252G/A gene polymorphism, known to be related to autoimmunity, in immune thrombocytopenia (ITP) patients. We also aimed to investigate the association between TNFB?+?252G/A polymorphism and susceptibility to develop persistent/chronic ITP.

Methods: One hundred pediatric ITP patients, as well as 50 age- and sex-matched healthy Egyptian subjects, were included. Genotyping of TNF-β gene (G252A) was done using the PCR-RFLP method.

Results: TNFB allele B2 frequency was (64%, 64/100) in controls, (69%, 138/200) in ITP patients, while the frequency of the variant allele B1 was 36% (36/100) in controls, (31%, 62/200) in ITP patients. TNFB genotype frequency in ITP patients showed equal frequency for B2B2 and B1B2 genotypes, (46%, 46/100), while B1B1 frequency was 8% (8/100). Among controls, frequencies of B2B2, B1B2 and B1B1 genotypes were 36% (18/50), 56% (28/50), and 8% (4/50), respectively. Odds ratio for the risk of developing ITP revealed no statistically significant risk, associated with any allele or genotype. No association was encountered between different genotypes and age, hematological parameters, gender, stage of the disease or response to treatment.

Discussion: Comparison between ITP patients and controls as regards TNFB allele and genotype frequencies showed no statistically significant difference. No increased risk for developing ITP was associated with any allele/genotype.

Conclusion: The risk of developing ITP was not related to the studied polymorphism.     

Correlation Between CASC8, SMAD7 Polymorphisms and the Susceptibility to Colorectal Cancer: An Updated Meta-Analysis Based on GWAS Results

Genome-wide association studies (GWASs) and a number of case–control studies have suggested that several single nucleotide polymorphisms (SNPs), rs7837328, rs7014346, rs6983267, rs10505477 on CASC8 gene and rs4939827, rs4464148, rs12953717 on SMAD7 gene are significantly correlated with the susceptibility to colorectal cancer (CRC). For the sake of clarifying the association, a meta-analysis was conducted and population heterogeneity was considered in the study.A total of 34 articles including 90 studies (168,471 cases and 163,223 controls) that evaluated the relationship between the CASC8, SMAD7 genes and the risk of CRC under the allelic model were reviewed. Also subgroup analysis was performed by ethnicity (Caucasian, Asian, and African) and all of the analyses were implemented in R 3.2.1 software.Pooled data from the meta-analysis revealed that the A allele of rs7837328, the A allele of rs7014346, the G allele of rs6983267, the A allele of rs10505477, the T allele of rs4939827, the T of rs4464148, and the T of rs12953717 were significantly associated with an increased risk of CRC under the allelic model. Additionally, subgroup analyses of 6 SNPs by ethnicity (rs4464148 excepted) witnessed that the A allele of rs7837328, the G allele of rs6983267, and the T of rs12953717 were notably associated with an increased risk of CRC among Caucasian and Asian. Furthermore, the A allele of rs7014346, the A allele of rs10505477, and the T allele of rs4939827 were significantly related with an elevated risk of CRC only among Caucasian.Our study suggested that for CASC8 gene, SNP of rs7837328 and rs6983267 are risk factors for CRC among both Caucasian and Asian whereas rs7014346 and rs10505477 are risky gene polymorphisms only among Caucasian. For SMAD7 gene, rs4939827 and rs4464148 are risk factors for CRC among Caucasian whereas rs12953717 could elevate the susceptibility to CRC in both Caucasian and Asian.     

Association between obesity-related adipokines and colorectal cancer:A case-control study and meta-analysis

AIM:To examine the association between obesityrelated adipokines(adiponectin,leptin,resistin,interleukin-6(IL-6),and tumor necrosis factor-α(TNF-α)and colorectal cancer(CRC)risk.METHODS:Serum levels of adipokines were measured in 100 CRC patients and age-and sex-matched controls for the data analysis.Unconditional logistic regression models were used for estimating ORs and95%CIs related to each adipokine.For the metaanalysis,studies published before July 2013 available on Medline/PubMed and EMBASE were retrieved.The analysis included a total of 17 relevant studies(including the present case-control study):nine studies on adiponectin and eight on leptin.The effect sizes of ORs and 95%CIs were estimated using RevMan 5.1.Heterogeneity was evaluated using Cochran’s Q-test and I2 statistics.RESULTS:Among the five adipokines,only resistin levels were significantly higher in cases than in controls(P<0.001).The case-control study results showed no association between adiponectin and CRC and a negative association between leptin and CRC.However,the results of the meta-analysis showed a significant inverse association between adiponectin and CRC(OR=0.91,95%CI:0.83-1.00,P=0.04)and no association between CRC and leptin.After stratification by study design,an inverse association between adiponectin and CRC was observed in prospective studies only(OR=0.90,95%CI:0.82-0.99,P=0.03),whereas the association between leptin and CRC was inconsistent(prospective studies:OR=1.14,95%CI:1.02-1.27,P=0.02 and retrospective studies:OR=0.47,95%CI:0.29-0.74,P=0.001).The associations of resistin and TNF-αwith CRC risk were positive,but no association was observed for IL-6.CONCLUSION:Our results suggest a negative association of leptin,positive associations of resistin and TNF-α,and null associations of adiponectin and IL-6with CRC.However,further studies with larger number of prospective approaches are needed.     

LBP and CD14 polymorphisms correlate with increased colorectal carcinoma risk in Han Chinese

AIM: To explore the associations of polymorphisms of lipopolysaccharide binding protein (LBP), cluster of differentiation 14 (CD14), toll-like receptor 4 (TLR-4), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) with the colorectal carcinoma (CRC) risk in Han Chinese. METHODS: Polymorphisms of LBP (rs1739654, rs223 2596, rs2232618), CD14 (rs77083413, rs4914), TLR-4 (rs5030719), IL-6 (rs13306435) and TNF-α (rs35131721) were genotyped in 479 cases of sporadic colorectal carcinoma and 486 healthy contr...     

-449 C>G polymorphism of NFKB1 gene,coding nuclear factor-kappa-B,is associated with the susceptibility to ulcerative colitis

AIM: To clarify the association between a polymorphism -449 C>G (rs72696119) in 5’-UTR of NFKB1 with ulcerative colitis (UC).METHODS: The studied population comprised 639 subjects, including patients with UC (UC cases, n = 174) and subjects without UC (controls, n = 465). We employed polymerase chain reaction-single strand conformation polymorphism to detect the gene polymorphism.RESULTS: The rs72696119 G allele frequencies in controls and UC cases were 33.4% and 38.5%, respectively (P = 0.10). Genotype frequency of the GG homozygote in UC cases was significantly higher than that in controls (P = 0.017), and the GG homozygote was significantly associated with susceptibility to UC [odds ratio (OR), 1.88; 95%CI, 1.13-3.14]. In male subjects, the GG homozygote was associated with an increased risk for UC (OR, 3.10; 95%CI, 1.47-6.54; P = 0.0053), whereas this association was not found in female subjects. In addition, the GG homozygote was significantly associated with the risk of non-continuous disease (OR, 2.06; 95%CI, 1.12-3.79; P = 0.029), not having total colitis (OR, 2.40; 95%CI, 1.09-3.80, P = 0.040), disease which developed before 20 years of age (OR, 2.80; 95%CI, 1.07-7.32, P = 0.041), no hospitalization (OR, 2.28; 95%CI, 1.29-4.05; P = 0.0090) and with a maximum of 8 or less on the UCDAI score (OR, 2.45; 95%CI, 1.23-4.93; P = 0.022).CONCLUSION: Our results provide evidence that NFKB1 polymorphism rs72696119 was significantly associated with the development of UC. This polymorphism influences the susceptibility to and pathophysiological features of UC.     

Interleukin-18 genetic polymorphisms contribute differentially to the susceptibility to Crohn’s disease

AIM: To investigate the correlation between interleukin-18 (IL-18) gene polymorphisms and the risk of developing Crohn’s disease (CD).METHODS: The PubMed, CISCOM, CINAHL, Web of Science, EBSCO, Cochrane Library, MEDLINE, EMBASE and CBM databases were searched without any language restrictions using combinations of keywords relating to CD and IL-18 for relevant articles published before November 1^st, 2013. Screening of the published studies retrieved from searches was based on our stringent inclusion and exclusion criteria and resulted in seven eligible studies for meta-analysis. A meta-analysis was conducted using a random-effects model with STATA 12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (95%CI) were calculated.RESULTS: Seven case-control studies, with a total of 1930 CD cases and 1930 healthy subjects, met our inclusion criteria. The results of our meta-analysis indicated that the IL-18 rs1946518 A>C and rs187238 G>C polymorphisms may correlate with an increased risk of CD under five genetic models (all P < 0.05). Furthermore, we observed positive associations between the IL-18 rs360718 A>C polymorphism and CD risk under three genetic models (C allele vs A allele: OR = 2.03, 95%CI: 1.20-3.43, P = 0.008; CC vs AA+AC: OR = 2.39, 95%CI: 1.2-4.43, P = 0.006; CC vs AC: OR = 2.31, 95%CI: 1.22-4.38, P = 0.010). However, such associations were not found for the IL-18 rs917997 C>T, codon 35 A>C and rs1946519 G>T polymorphisms (all P > 0.05). A subgroup analysis was conducted to investigate the effect of ethnicity on an individual’s susceptibility to CD. Our results revealed positive correlations between IL-18 genetic polymorphisms and an increased risk of CD among Asians and Africans (all P < 0.05), but not among Caucasians (all P > 0.05).CONCLUSION: This meta-analysis indicated that the IL-18 rs1946518 A>C, rs187238 G>C and rs360718 A>C polymorphisms may contribute to susceptibility to CD, especially among Asians and Africans. These polymorphisms are known to reduce IL-18 mRNA and protein levels.     

RAGE gene three polymorphisms with Crohn's disease susceptibility in Chinese Han population

AIM: To investigate the association of three polymorphisms in the receptor for advanced glycation end product (RAGE) gene with Crohn’s disease (CD) risk in a Chinese population.METHODS: A hospital-based case-control association study involving 312 CD patients and 479 healthy controls was conducted. Peripheral blood samples were collected from 791 study subjects, and genomic DNA was extracted. Genotyping was performed using polymerase chain reaction-ligase detection reaction method. The association between polymorphic genotype and CD predisposition was determined using odds ratio and 95% confidence interval (CI). Data were analyzed using Haplo.stats program.RESULTS: Significant differences were observed between patients and controls in allele/genotype distributions of rs1800624 (P_allele=0.012; P_genotype=0.005) and in allele distributions of rs2070600 (P=0.02). The risk for CD associated with the rs1800624-A mutant allele decreased by 36% (95%CI: 0.47-0.88, P = 0.005) under the additive model and by 35% (95%CI: 0.46-0.91, P=0.013) under the dominant model. Carriers of rs2070600-A mutant allele showed a 37% (95%CI: 1.02-1.83, P=0.036) increased risk of developing CD relative to the GG genotype carriers. In haplotype analysis, haplotype T-A-G (in the order rs1800625, rs1800624, and rs2070600) decreased the odds of CD by 33% (95%CI: 0.49-0.94, P=0.018).CONCLUSION: CD is an immune-related disease with genetic predisposition. Genetic defects in the RAGE gene are strongly associated with CD in Chinese population.     

HIF-1α-1790G>A polymorphism significantly increases the risk of digestive tract cancer:A meta-analysis

AIM:To investigate the association between hypoxiainducible factor-1α(HIF-1α) polymorphisms(-1772CT and-1790GA) and the risk of digestive tract cancer.METHODS:A total of 13 eligible studies were retrieved from Pub Med,EMBASE,and the ChinaNational Knowledge Infrastructure database.The odds ratios(ORs) and 95% confidence intervals(CIs) were calculated to estimate the strength of the associations.RESULTS:By pooling the eligible studies,we found that the HIF-1α-1772CT polymorphism was not associated with the risk of developing digestive tract cancer(dominant comparison,OR:1.156; 95%CI:0.839-1.593; P heterogeneity = 0.007),and no significant association was found in the Asian population or the Caucasian population.However,for the-1790GA polymorphism,carriers of the variant-1790 A allele had a significantly increased risk of digestive tract cancer compared with those with the wildtype-1790 G allele(dominant comparison,OR:3.252; 95%CI:1.661-6.368; P heterogeneity 0.001).Additionally,this increased risk of digestive cancer was only detected in Asians; there was no significant association in Caucasians.CONCLUSION:This meta-analysis demonstrates that the HIF-1α-1790GA polymorphism is associated with a significantly increased risk of digestive tract cancer,while the-1772CT polymorphism is not.     

Macrophage migration inhibitory factor gene polymorphisms in inflammatory bowel disease: An association study in New Zealand Caucasians and meta-analysis

AIM:To investigate the association of macrophage migration inhibitory factor(MIF)promoter polymorphisms with inflammatory bowel disease(IBD)risk.METHODS:One thousand and six New Zealand Caucasian cases and 540 Caucasian controls were genotyped for the MIF SNP-173G>C(rs755622)and the repeat polymorphism CATT5-8(rs5844572)using a predesigned TaqMan SNP assay and capillary electrophoresis,respectively.Data were analysed for single site and haplotype association with IBD risk and phenotype.Meta-analysis was employed,to assess cumulative evidence of association of MIF-173G>C with IBD.All published genotype data for MIF-173G>C in IBD were identified using PubMed and subsequently searching the references of all PubMed-identified studies.Imputed genotypes for MIF-173G>C were generated from the Wellcome Trust Case Control Consortium(and National Institute of Diabetes and Digestive and Kidney Diseases).Separate meta-analyses were performed on Caucasian Crohn’s disease(CD)(3863 patients,6031controls),Caucasian ulcerative colitis(UC)(1260 patients,1987 controls),and East Asian UC(416 patients and 789 controls)datasets using the Mantel-Haenszel method.The New Zealand dataset had 93%power,and the meta-analyses had 100%power to detect an effect size of OR=1.40 atα=0.05,respectively.RESULTS:In our New Zealand dataset,single-site analysis found no evidence of association of MIF polymorphisms with overall risk of CD,UC,and IBD or disease phenotype(all P values>0.05).Haplotype analysis found the CATT5/-173C haplotype occurred at a higher frequency in New Zealand controls compared to IBD patients(0.6 vs 0.01;P=0.03,OR=0.22;95%CI:0.05-0.99),but this association did not survive bonferroni correction.Meta-analysis of our New Zealand MIF-173G>C data with data from seven additional Caucasian datasets using a random effects model found no association of MIF polymorphisms with CD,UC,or overall IBD.Similarly,meta-analysis of all published MIF-173G>C data from East Asian datasets(416UC patients,789 controls)found no     

Association between TNF-a and IL-1β genotypes vs Helicobacter pylori infection in Indonesia

AIM:To investigate the correlation between the Helicobacter pylori(H.pylori)infection and host genetic background of healthy populations in Indonesia.METHODS:In March 2007,epidemiological studies were undertaken on the general population of a city in Indonesia(Mataram,Lombok).The participants included 107 men and 187 women,whose ages ranged from6 to 74 years old,with an average age of 34.0(±14.4)(±SD).The H.pylori of subject by UBT method determination,and through the polymerase chain reaction with confronting two-pair primers(PCR-CTPP)method parsing the single nucleotide polymorphism of interleukin(IL)-8,IL-4,IL-1β,CD14,tumor necrosis factor(TNF-a)and tyrosine-protein phosphates non-receptor type 11(PTPN11)genotypes.The experimental data were analyzed by the statistical software SAS.RESULTS:The H.pylori infection rates in the healthy Indonesian population studied were 8.4%for men and12.8%for women;no obvious differences were noted for H.pylori infection rates by sex or age.TC genotypes of IL-4,TC and CC genotypes of TNF-a,and GA genotypes of PTPN11,were higher in frequency.Both CC and TC genotype of TNF-a T-1031C loci featured higher expressions in the healthy Indonesian population Indonesia studied of(OR=1.99;95%CI:0.67-5.89)and(OR=1.66;95%CI:0.73-3.76),respectively.C allele of IL-1βT-31C gene locus was at a higher risk(OR=1.11;95%CI:0.70-1.73)of H.pylori infection,but no statistical significance was found in our study.CONCLUSION:We reveal that the association between the TNF-a and IL-1βgenotypes may be the susceptibility of H.pylori in the studied population.     

APE1 polymorphisms are associated with colorectal cancer susceptibility in Chinese Hans

AIM: To study the association between four base excision repair gene polymorphisms and colorectal cancer risk in a Chinese population.METHODS: Two hundred forty-seven colorectal cancer (CRC) patients and three hundred cancer-free controls were enrolled in this study. Four polymorphisms (OGG1 Ser326Cys, APE1 Asp148Glu, -141T/G in the promoter region, and XRCC1 Arg399Gln) in components of the base excision repair pathway were determined in patient blood samples using polymerase chain reaction with confronting two-pair primers. The baseline information included age, gender, family history of cancer, and three behavioral factors [smoking status, alcohol consumption, and body mass index (BMI)]. χ² tests were used to assess the Hardy-Weinberg equilibrium, the distributions of baseline characteristics, and the four gene polymorphisms between the cases and controls. Multivariate logistic regression analyses were conducted to analyze the correlations between the four polymorphisms and CRC risk, adjusted by the baseline characteristics. Likelihood ratio tests were performed to analyze the gene-behavior interactions of smoking status, alcohol consumption, and BMI on polymorphisms and CRC susceptibility.RESULTS: The APE1 148 Glu/Glu genotype was significantly associated with an increased risk of colorectal cancer (OR = 2.411, 95%CI: 1.497-3.886, P < 0.001 relative to Asp/Asp genotype). There were no associations between OGG1, XRCC1, or APE1 promoter polymorphisms and CRC risk. A multivariate analysis including three behavioral factors showed that the APE1 148 Glu/Glu genotype was associated with an increased risk for CRC among both smokers and non-smokers, non-drinkers and individuals with a BMI ≥ 25 kg/m² (ORs = 2.356, 3.299, 2.654, and 2.581, respectively). The XRCC1 399 Arg/Gln genotype was associated with a decreased risk of CRC among smokers and drinkers (OR = 0.289, 95%CI: 0.152-0.548, P < 0.001, and OR = 0.327, 95%CI: 0.158-0.673, P < 0.05, respectively). The APE1 promoter polymorphism -141 T/G genotype was associated with a reduced risk of colorectal cancer among subjects with a BMI < 25 kg/m² (OR = 0.214, 95%CI: 0.069-0.660, P < 0.05 relative to T/T genotype). There were significant gene-behavior interactions between smoking status and XRCC1 Arg399Gln, as well as BMI and APE1 -141T/G polymorphism (all P < 0.05).CONCLUSION: APE1 Asp148Glu is associated with increased CRC risk and smoking alters the association between XRCC1 Arg399Gln and CRC risk in the Chinese Han population.     

唐山地区汉族人群白细胞介素6基因-572C/G多态性与脑梗死关系的研究

目的探讨唐山地区汉族部分人群白细胞介素6(IL-6)基因-572C/G多态性与脑梗死的关系。方法采用多聚酶链反应-限制性片段长度多态性,检测118例首次新发脑梗死患者(脑梗死组)和154例健康体检者(对照组)IL-6基因-572C/G多态性位点频率,分析基因型与脑梗死的相关性。结果脑梗死组患者-572位点CC、CG、GG基因型频率分别为50.85%、41.53%、7.63%;对照组CC、CG、GG基因型频率分别为65.58%、31.82%、2.60%。脑梗死组和对照组-572位点C等位基因频率分别为71.61%、81.49%;G等位基因频率分别为28.39%、18.51%,差异有统计学意义(P0.05)。CG、GG基因型人群患脑梗死的风险分别是CC基因型的1.683倍(95% CI:1.012～2.800,P0.05)和3.788倍(95% CI:1.11 8～12.833,P0.05)。多因素logistic回归分析显示,-572G等位基因是脑梗死发生的独立危险因素。结论唐山地区汉族部分人群中存在IL-6基因-572C/G多态性,可能与脑梗死有关,-572G等位基因可能是脑梗死发病的易感基因。     

Relation between common polymorphisms in genes related to inflammatory response and colorectal cancer

AIM: To investigate the association between common single nucleotide polymorphisms (SNPs) in inflammatory response-related genes such as interleukin (IL)-6, IL-8, tumor necrosis factor a (TNFα), peroxisome proliferators-activated receptorγ(PPARγ), intercellular adhesion molecule-1 (ICAM-1) and the risk of colorectal cancer (CRC) in a group of Greek patients. METHODS: The study group consisted of 222 CRC patients and 200 healthy controls. Genotyping was performed using allele-specific PCR of PRC-RFLP and the results were confirmed by sequencing. We studied the association of SNPs in the IL-6 (-174G > C), IL-8 (-251T > A), TNFα(-308G > A), ICAM-1 (R241G and K469E), and PPARγ(Prol2Ala) genes and the risk of CRC. RESULTS: The IL-6 -174G, R241 and K469 alleles of ICAM-1 were associated with increased risk of CRC (OR = 1.77, 95% CI: 1.34-2.34; OR = 1.83, 95% CI: 1.23-2.72; and OR = 1.35, 95% CI: 1.03-1.77 respectively). The IL-8 and TNFαpolymorphisms had no effect. Whereas the PPARγPro12 genotype was associated with increased risk of disease (OR = 1.78, 95% CI: 1.25-2.49). CONCLUSION: The association between common SNPs in immunologic response-related genes and CRC is reported in the present study. Apart from shedding light on the mechanisms of malignancy initiation and progression, SNPs may improve appropriate screening for sub-populations at risk.     

Lack of association between apolipoprotein C3 gene polymorphisms and risk of nonalcoholic fatty liver disease in a Chinese Han population

AIM:To investigate the association between two polymorphisms of apolipoprotein C3(APOC3)and risk of nonalcoholic fatty liver disease(NAFLD)in a Chinese Han population.METHODS:Genotypes for rs2854116 and rs2854117in APOC3 and the known rs738409 in patatin-like phospholipase domain-containing protein 3(PNPLA3)in 390patients with NAFLD and 409 control subjects were determined by sequencing and polymerase chain reaction analysis.Serum lipid profiles were determined using biochemical methods,and an index of insulin resistance(IR,HOMA-IR),serum APOC3 concentrations and total antioxidant status(TAS)were also assessed.RESULTS:No significant differences in genotype and allele frequencies of rs2854116 and rs2854117 were found between the NAFLD population and the controls(P>0.05).The OR for the association between-455Cand-482T allele carriers and the risk of NAFLD were1.06(95%CI:0.72-1.57,P>0.05)and 1.00(95%CI:0.68-1.48,P>0.05),respectively.The variant carriers did not have a significantly increased risk of NAFLD or elevated clinical and biochemical parameters such as APOC3 concentrations,IR(1.42±0.43 vs 1.48±0.52,P>0.05),liver enzymes and TAS(13.94±2.01vs 14.38±1.92,P>0.05)compared with the controls.Moreover,the results were similar when testing was carried out independent of the genetic variation in PNPLA3.CONCLUSION:The two polymorphisms of the APOC3gene are not associated with a risk of NAFLD,or with lipid profiles,IR and oxidative stress in the Chinese Han population.     

CDH1 promoter polymorphism （-347G→GA） is a possible prognostic factor in sporadic colorectal cancer

AIM: To investigate the role of the -347G→GA polymorphism in the progression of colorectal cancer (CRC).METHODS: We designed a case-control study based on a population of CRC patients in China and normal healthy controls with no history of tumors or inherited diseases. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analyses were used to genotype the variants, and immunohistochemical staining was performed to measure the expression of E-cadherin in different allele cases among the CRC patients and normal controls.RESULTS: The GA-allele (G/GA heterozygous and GA/GA homozygous) did not increase the risk of CRC compared with the G-allele (OR = 1.232, 95% CI = 0.898-1.691). However, the frequencies of the GA-allele were higher in poorly differentiated (P = 0.002) and proximal (P = 0.019) CRC patients than in normal controls. We also observed that E-cadherin expression was lower in poorly differentiated CRC patients than in well differentiated CRC patients (P = 0.001). Furthermore, E-cadherin expression was lower for the GA-allele than for the G-allele (G/G heterozygous) in CRC patients (P = 0.018). In contrast, there was no significant difference in E-cadherin expression for the G-allele and GA-allele in normal controls (P = 0.292).CONCLUSION: The -347G→GA promoter polymorphism in E-cadherin gene is associated with specific CRC features, and may be a prognostic factor rather than a susceptibility factor during the progression of CRC.     

Association of CD14/-260 polymorphism with gastric cancer risk in Highland Tibetans

AIM:To investigate the relationship between CD14-260and-651 polymorphisms and the risk of developing gastric cancer.METHODS:DNA was extracted from peripheral blood samples obtained from 225 Tibetans with gastric cancer and 237 healthy Tibetans,and analyzed using the polymerase chain reaction/ligase detection(PCR/LDR)method to determine the genotypes at-260 and-651loci of the CD14 promoter.The allele frequencies,genotype frequencies,and haplotypes were analyzed for their association with gastric cancer risk using online SHEsis software.The luciferase reporter assay and point mutation analysis were used to construct in vitro plasmids expressing a C/T homozygote at the-260 lo-cus of the CD14 promoter.RESULTS:The frequencies of CC,CT and TT genotypes in the CD14-260 C/T locus in gastric cancer patients were 19.1%,38.7%and 42.2%,respectively,whereas they were 33.3%,32.5%and 34.2%,respectively,in healthy control subjects.CT genotype carriers were more frequently found among gastric cancer patients than healthy controls(OR=2.076;95%CI:1.282-3.360).Also,TT genotype carriers were more frequently found among gastric cancer patients(OR=2.155;95%CI:1.340-3.466).Compared to the C allele of CD14/-260,the T allele was associated with an increased risk for gastric cancer(OR=1.574;95%CI:1.121-2.045).Furthermore,the frequencies of CC,CT and TT in the CD14-651 C/T locus in gastric cancer patients were 64.4%,29.3%and 6.2%,respectively,while they were 56.5%,35.0%and 8.4%,respectively,in the healthy control subjects(P>0.05).Data obtained using the luciferase reporter assay showed that the p260T homozygote was associated with greater CD14 promoter activity(P<0.01).CONCLUSION:CD14/-260 polymorphism is associated with gastric cancer risk in Highland Tibetans and affects CD14 promoter activity,thereby regulating CD14expression.