Risk modification of colorectal cancer susceptibility by interleukin-8 -251T>A polymorphism in Malaysians

AIM: To investigate the allele and genotype frequencies and associated risk of interleukin (IL)-8 -251T>A polymorphism on colorectal cancer (CRC) susceptibility risk.METHODS: Peripheral blood samples of 255 normal controls and 255 clinically and histopathologically confirmed CRC patients were genotyped for IL-8 -251T>A polymorphism employing allele-specific polymerase chain reaction. The relative association of variant allele and genotypes with CRC susceptibility risk was determined by calculating the odds ratios (ORs). Corresponding χ² tests on the CRC patients and controls were carried out and 95% confidence intervals (CIs) were determined using Fisher’s exact test. The allele frequencies and its risk association were calculated using FAMHAP, haplotype association analysis software.RESULTS: On comparing the frequencies of genotypes of patients and controls, the homozygous variant AA was significantly higher in CRC patients (P = 0.002) compared to controls. Investigation on the association of the polymorphic genotypes with CRC susceptibility risk, showed that the homozygous variant IL-8 -251AA had a significantly increased risk with OR 3.600 (95% CI: 1.550-8.481, P = 0.001). In the case of allele frequencies, variant allele A of IL-8 -251 showed a significantly increased risk of CRC predisposition with OR 1.32 (95% CI: 1.03-1.69, P = 0.003).CONCLUSION: Variant allele and genotype of IL-8 (-251T>A) was significantly associated with CRC susceptibility risk and could be considered as a high-risk variant for CRC predisposition.     

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.     

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.     

Association of colorectal cancer susceptibility variants with esophageal cancer in a Chinese population

AIM: To investigate the association between colorectal cancer(CRC) genetic susceptibility variants and esophageal cancer in a Chinese Han population.METHODS: A case-control study was conducted including 360 esophageal cancer patients and310 healthy controls. Thirty-one single-nucleotide polymorphisms(SNPs) associated with CRC risk from previous genome-wide association studies were analyzed. SNPs were genotyped using Sequenom Mass-ARRAY technology, and genotypic frequencies in controls were tested for departure from HardyWeinberg equilibrium using a Fisher's exact test. The allelic frequencies were compared between cases and controls using a χ 2 test. Associations between the SNPs and the risk of esophageal cancer were tested using various genetic models(codominant, dominant,recessive, overdominant, and additive). ORs and95%CIs were calculated by unconditional logistic regression with adjustments for age and sex.RESULTS: The minor alleles of rs1321311 and rs4444235 were associated with a 1.53-fold(95%CI:1.15-2.06; P = 0.004) and 1.28-fold(95%CI: 1.03-1.60;P = 0.028) increased risk of esophageal cancer in the allelic model analysis, respectively. In the genetic model analysis, the C/C genotype of rs3802842 was associated with a reduced risk of esophageal cancer in the codominant model(OR = 0.52, 95%CI:0.31-0.88; P = 0.033) and recessive model(OR =0.55, 95%CI: 0.34-0.87; P = 0.010). The rs4939827C/T-T/T genotype was associated with a 0.67-fold(95%CI: 0.46-0.98; P = 0.038) decreased esophageal cancer risk under the dominant model. In addition,rs6687758, rs1321311, and rs4444235 were associated with an increased risk. In particular, the T/T genotype of rs1321311 was associated with an 8.06-fold(95%CI: 1.96-33.07; P = 0.004) increased risk in the codominant model.CONCLUSION: These results provide evidence that known genetic variants associated with CRC risk confer risk for esophageal cancer, and may bring risk for other digestive system tumors.     

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.     

Colorectal cancer mortality in Inner Mongolia between 2008 and 2012

AIM: To determine the extent of colorectal cancer (CRC) mortality and the association between demographic characteristics and CRC mortality in Inner Mongolia.METHODS: Data were collected from the Death Registry System, maintained by the Inner Mongolia Centers for Disease Control and Prevention, from 2008 to 2012. Deaths were classified according to the International Classification of Disease, 10^th Revision. Years of life lost, average years of life lost (AYLL), and mortality were calculated over the five years between 2008 and 2012. A conditional logistic regression model was used to analyze the association between marital status, occupational status, education level, area of residence, and the risk of CRC.RESULTS: The AYLL of CRC was 17.39 years. The average mortality of CRC was 5.6/100000. People living in urban areas and having a higher education level had a significantly higher risk of CRC (OR = 1.74 and 95%CI: 1.29-2.35, P < 0.001 and OR = 2.39, 95%CI: 1.76-3.25, P < 0.001, respectively). People who were employed had a lower risk of CRC (OR = 0.64, 95%CI: 0.48-0.86, P = 0.003). The mortality of CRC was positively correlated with the education level (P < 0.001). No statistically significant association was observed between marital status and CRC risk (P = 0.259).CONCLUSION: Living in urban areas, higher education level and unemployment are associated with CRC mortality in Inner Mongolia.     

Xeroderma pigmentosum group D polymorphisms and esophageal cancer susceptibility: A meta-analysis based on case-control studies

AIM: To clarify the effects of the xeroderma pigmentosum group D(XPD) Asp312 Asn and Lys751 Gln gene polymorphisms on the risk of esophageal cancer(EC).METHODS: A computerised literature search was conducted to identify the relevant studies from the PUBMED and EMBASE databases, reviews, and reference lists of relevant articles. Odds ratios(ORs) with 95% confidence intervals(CIs) were used to assess the associations between the XPD Asp312 Asn and/or Lys751 Gln polymorphisms and EC susceptibility. Statistical analyses were performed using the software Stata 12.0. A fixed or random effects model was selected based on a heterogeneity test. Publication bias was estimated using funnel plots and Egger’s linear regression method. Subgroup analyses were performed based on histological type and ethnicity.RESULTS: Thirteen case-control studies with a total of 10 comparisons for the Asp312 Asn polymorphism, including 2373 cases and 3175 controls, and 15 comparisons for the Lys751 Gln polymorphism, including 3226 cases and 5237 controls, were recruited for the meta-analysis. In terms of the XPD Asp312 Asn polymorphism, significantly increased EC risks were identified in the Asp/Asn vs Asp/Asp comparison(OR = 1.17, 95%CI: 1.02-1.33, P = 0.03) and in the dominantmodel comparison(Asn/Asn+Asp/Asn vs Asp/Asp: OR = 1.18, 95%CI: 1.04-1.34, P = 0.01). However, no significant associations were found in the Asn/Asn vs Asp/Asp comparison(OR = 1.30, 95%CI: 1.00-1.70, P = 0.05) or in the recessive-model comparison(Asn/Asn vs Asp/Asn + Asp/Asp: OR = 1.17, 95%CI: 0.91-1.50, P = 0.22). In terms of the XPD Lys751 Gln polymorphism, a significant association with EC susceptibility was found under the recessive model(Gln/Gln vs Lys/Gln+Lys/Lys: OR = 1.21, 95%CI: 1.02-1.43, P = 0.03). However, no associations were identified in the other comparisons(co-dominant model: Lys/Gln vs Lys/Lys: OR = 1.11, 95%CI: 0.94-1.31, P = 0.20; Gln/Gln vs Lys/Lys: OR = 1.31, 95%CI: 0.98-1.75, P = 0.07; dominant model: OR = 1.14, 95%CI: 0.96-1.35, P = 0.14).CONCLUSION: The results of this meta-analysis suggest that the XPD Asp312 Asn and Lys751 Gln gene polymorphisms are associated with a significantly increased risk for EC.     

X线损伤交叉互补基因1多态性与结直肠癌易感性研究

目的 探讨DNA修复酶X线损伤交叉互补基因1(XRCC1 )外显子三个位点的基因多态性(Arg194Trp 、Arg280His、Arg399Gln)与结直肠癌(CRC)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性(PCR-RFLP)分析方法,采用病例-对照研究,对250例CRC患者(病例组,其中结肠癌128例,直肠癌122例)和213名健康人(对照组)的XRCC1基因三个位点的多态性进行了检测,采用SPSS 11.0软件包统计分析各位点的基因型分布和等位基因频率.结果 XRCC1基因194和399二个位点的各基因型频率在两组间分布差异均无统计学意义(P值均>0.05),但病例组XRCC1基因280 Arg/His基因型频率较对照组显著增高(校正后OR=1.66,95%CI:1.01～2.73,P=0.047).在直肠癌患者组中,280Arg/His基因型频率较对照组显著增高(OR=1.82,95%CI:1.02～3.27),携等位基因280His(Arg280His +His280His)的CRC患者的频率显著高于其在对照组中的频率(校正后OR=1.85,95%CI:1.06～3.22),而在结肠癌患者中风险系数相对较低且差异无统计学意义(校正后OR=1.31,95%CI:0.74～2.35).结论 XRCC1 Arg194Trp和 Arg399Gln基因多态性与结肠癌易感性无关,但280Arg/His基因型能增加CRC易感性,等位基因280His是直肠癌风险因素.

Abstract：

Objective To investigate the correlation between three gene locus polymorphisms of X-ray repair cross-complementary protein 1 (XRCC1) exon (Arg194Trp, Arg280His and Arg399Gln) and the risk of colorectal cancer (CRC). Methods A case-control study was performed in 250 CRC patients (case group, 128 colon cancer patients and 122 rectal cancer patients) and 213 healthy individuals (control group). The three gene locus polymorphism of XRCC1 was tested by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. The genotype distribution and allele frequency of each locus was analyzed with SPSS 10.0 software. Results There was no significant difference in allele frequency of XRCC1 at 194 and 399 loci (P > 0.05). However, the 280 Arg/His allele frequency of XRCC1 was higher in case group than that in control group (OR=1.66,95%CI:1.01~2.73,P=0.047). The 280Arg/His allele frequency was higher in rectal cancer group than that in control group (OR =1.82,95%CI:1.02~3.27). The frequency of 280His allele (Arg280His and His280His) was higher in case group than that in control group (OR=1.85,95%CI:1.06~3.22). However, it was a relative low risk factor of colon cancer and there was no significant difference between colon cancer group and control group (OR=1.85, 95%CI:1.06~3.22). Conclusions There was no correlation between XRCC1 Arg194Trp and Arg399Gln polymorpohisms and the risk of CRC. However, 280Arg/His genotype may increase the risk of CRC, and 280His allele is a risk factor of rectal cancer.     

XPC gene variants: a risk factor for recurrence of urothelial bladder carcinoma in patients on BCG immunotherapy

Purpose

To investigate the association between two Xeroderma pigmentosum group C polymorphism (XPC Lys939Gln and insertion/deletion PAT ?/+ in intron 9) and bladder cancer (BC) susceptibility.

Materials and methods

Genotyping was performed in 208 BC patients and 245 controls by PCR–RFLP method.

Results

XPC PAT +/+ genotype was associated with elevated risk of BC (p = 0.021, OR = 2.49). XPC Lys939Gln AC + CC genotype was significantly associated with risk in invasive stage of BC (p = 0.041, OR = 2.52). Haplotype analysis revealed that variant genotypes C of XPC Lys939Gln and + of PAT, C+ were significantly associated with risk of BC (p = 0.004, OR = 1.70). The CC genotype of Lys939Gln was associated with high risk for recurrence in BCG-treated patients (HR = 3.21, p = 0.036) thus, showing reduced recurrence-free survival (AC + CC/AA = 36/60 months; log rank p = 0.045).

Conclusion

Polymorphisms and haplotypes in XPC appear to influence susceptibility to BC risk. The variant C allele at Lys939Gln may be responsible for early recurrence in BCG-treated patients.     

Relationship between interleukin-6 polymorphism and susceptibility to chronic hepatitis B virus infection

AIM:To identify the relationship between tag single nucleotide polymorphisms(tag SNPs) of interleukin-6(IL-6) gene and susceptibility to chronic hepatitis B virus(HBV) infection in a Han Chinese population.METHODS:We performed a case-control study of501 Chinese patients with chronic HBV infection and301 self-limiting HBV-infected individuals as controls.Genomic DNA was isolated from the whole blood of all subjects using phenol/chloroform with MaXtract highdensity tubes. Tag SNPs were identified using genotype data from the panel(Han Chinese in Beijing) of the phase II HapMap Project. Four tag SNPs in IL-6(rs17147230A/T,rs2066992G/T,rs2069837A/G and rs2069852A/G) were genotyped by the Multiplex Snapshot technique. The genotype and allele frequencies were calculated and analyzed.RESULTS:Five haplotypes were involved in the analysis,with frequencies higher than 0.03. One of the haplotypes,TTAA,was significantly different between the two groups. Overall haplotype P values were:ATAA,P = 0.605,OR(95%CI) = 1.056(0.860-1.297); TGAG,P = 0.385,OR(95%CI) = 1.179(0.813-1.709); TGGG,P = 0.549,OR(95%CI) = 1.087(0.827-1.429); TTAA,P = 0.004,OR(95%CI) = 0.655(0.491-0.873); TTAG,P = 0.266,OR(95%CI) = 1.272(0.832-1.944). However,the four SNPs showed no significant genotype/allele associations with susceptibility to chronic HBV infection. Overall allele P values were:rs17147230,P = 0.696,OR(95%CI) = 1.041(0.850-1.276); rs2066992,P = 0.460,OR(95%CI)= 1.090(0.868-1.369); rs2069837,P = 0.898,OR(95%CI) = 0.983(0.759-1.274); rs2069852,P = 0.165,OR(95%CI) = 0.859(0.693-1.064). Overall genotype P values were:rs17147230,P = 0.625; rs2066992,P= 0.500; rs2069837,P = 0.853; and rs2069852,P =0.380.CONCLUSION:The four tag SNPs of IL-6 gene may be associated with susceptibility to chronic HBV infection in the Han Chinese population.     

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.     

-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.     

Elevated risk of colorectal cancer associated with the AA genotype of the cyclin D1 A870G polymorphism in an Indian population

Purpose: To investigate whether the common cyclin D1 (CCND1) A870G polymorphism is a risk factor for colorectal cancer (CRC) in an Indian population. Methods: In this study, 301 newly diagnosed CRC patients and 291 healthy control subjects were genotyped by the PCR-RFLP method. Genotype frequencies were compared between cases and controls, and the association of genotypes with CRC was studied. Results: The CCND1 870 A allele was more frequently observed in CRC patients than controls (0.63 vs. 0.56, P=0.01), and after adjustment for age, sex, smoking habits, family history, family income and the consumption of meat, fish, vegetables and fruit, an increased risk was observed for the AA genotype compared to the GG+AG genotype (OR=1.56; 95% CI: 1.10–2.21). The increased risk were also found for colon (OR=1.96; 95% CI: 1.08–3.57) and rectal cancer (OR=1.51; 95% CI: 1.04–2.19). No correlation was observed between genotypes and age of diagnosis of CRC (49.9, 48.7 and 49.4 years for the GG, AG and AA genotypes, respectively; P=0.84). Multivariate analysis also revealed a stronger positive association with the AA genotype among patients with high meat intake (OR=2.67; 95% CI: 1.29–5.51), and particularly significant inverse associations with the GG+AG genotypes were also found for those with high vegetable consumption (OR=0.46; 95% CI: 0.27–0.79 of 2–3 servings/day, and OR=0.31; 95% CI: 0.18–0.53 for >3 servings/day) and fish intake (OR=0.48; 95% CI: 0.28–0.82). Conclusion: These data support the hypothesis that the CCND1 A870G polymorphism may increase the risk of CRC in our Indian population.     

Association of Helicobacter pylori babA2 with peptic ulcer disease and gastric cancer

AIM: To investigate the association between babA2 gene and peptic ulcer disease (PUD) and gastric cancer (GC) in Helicobacter pylori -infected populations. METHODS: We evaluated the relationship between babA2 and clinical outcomes (PUD and GC) using a meta-analysis. A literature search was performed using the PubMed and Web of Science databases for relevant case-control studies that met the defined inclusion criteria. The ORs and 95%CIs were calculated to estimate the association between babA2 genotype and clinical outcomes. A fixed-effect or random-effect model was performed depending on the absence or presence of significant heterogeneity. RESULTS: A total of 25 articles with 38 studies met the inclusion criteria and were finally included in this metaanalysis. The results showed that the babA2 genotype was significantly associated with an increased risk of PUD (OR = 2.069, 95%CI: 1.530-2.794, P < 0.001) and especially in the subgroup of duodenal ulcer (OR = 1.588, 95%CI: 1.141-2.209, P = 0.006). Moreover, a significant association between babA2 gene and PUD and duodenal ulcer (OR = 2.739, 95%CI: 1.860-4.032, P < 0.001; OR = 2.239, 95%CI: 1.468-3.415, P < 0.001, respectively) was observed in western countries but not in Asian countries. CONCLUSION: We demonstrated that the presence of babA2 may be associated with increased risks for PUD, especially duodenal ulcer, in western countries.     

Evaluation of the colorectal cancer risk conferred by rare UNC5C alleles

AIM:To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer(CRC).METHODS:We screened patients with familial CRC forms as well as patients with sporadic CRCs.In a first time,we analyzed exon 11 of the UNC5C gene in 120unrelated patients with suspected hereditary CRC,58patients with suspected Lynch-associated cancer or polyposis,and 132 index cases of Lynch syndrome families with a characterized mutation in a DNA mismatch repair(MMR).Next,1023 patients with sporadic CRC and1121 healthy individuals were screened for the variants identified in patients with familial cancer.RESULTS:Of 120 patients with familial CRC of unknown etiology,one carried the previously reported mis-sense mutation p.Arg603Cys(R603C)and another exhibited the unreported variant of unknown significance p.Thr617Ile(T617I).The p.Ala628Lys(A628K)mutation previously described as the main UNC5C risk variant for familial CRC was not detected in any cases of familial CRC of unknown etiology,but was present in a patient with familial gastric cancer and in two Lynch syndrome patients in co-occurrence with MMR mutations.A statistically non-significant increase in cancer risk was identified in familial CRC and/or other Lynchassociated cancers(1/178 patients vs 2/1121 healthy controls,OR=3.2,95%CI:0.29-35.05,P=0.348)and in sporadic CRCs(4/1023 patients vs 2/1121 healthy controls,OR=2.2,95%CI:0.40-12.02,P=0.364).CONCLUSION:We confirm that UNC5C mutations are very rare in familial and sporadic CRCs,but further investigations are needed to justify routine UNC5C testing for diagnostic purposes.     

Susceptibility to ulcerative colitis in Hungarian patients determined by gene-gene interactions

AIM:To study the inflammatory bowel disease-5 locus（IBD5）and interleukin-23 receptor（IL23R）gene variants in UC patients and test for gene-gene interaction.METHODS:The study population（n=625）was comprised of 320 unrelated ulcerative colitis（UC）patients with Caucasian origin and 316 age-and gendermatched,healthy controls.Five variants in the IBD5 locus（IGR2198a₁ rs11739135,IGR2096a₁ rs12521868,IGR2230a₁ rs17622208,SLC22A4 rs1050152 and SLC22A5 rs2631367）and two of the IL23R gene（rs1004819,rs2201841）were analysed.PCR and restriction fragment length polymorphism methods were used for genotyping,the SLC22A4 rs1050152 genotypes were determined by direct sequencing.Interactions and specific genotype combinations of the seven variants were tested by binary logistic regression analysis.The IL23R genotypes were stratified by IBD5 genotypes for further interaction analyses.RESULTS:For the IL23R rs1004819 A allele we found significantly higher allele frequency（P=0.032）in UC patients compared to control subjects.The SNP rs1004819 showed significant association with UC risk for carriers（P=0.004,OR=1.606;95%CI:1.160-2.223）and the SNP rs2201841 for homozygotes（P=0.030,OR=1.983;95%CI:1.069-3.678）.Individually none of the IBD5 markers conferred risk to UC development.There was no evidence for statistical interaction either between IBD5 loci and IL23R genes using logistic regression analysis.After genotype stratification,we could detect a positive association on the background of rs1004819 A allele for SLC22A4 T,SLC22A5 C,IGR2198a₁ C or IGR2096a₁ T allele,the highest OR was calculated in the presence of SLC22A4T allele（P=0.005,OR=2.015;95%CI:1.230-3.300）.There was no association with UC for any combinations of rs1004819 and IGR2230a₁.The IL23R rs2201841homozygous genotype and IBD5 carrier status together did not confer susceptibility for UC.CONCLUSION:The present study has shown that UC susceptibility genes are likely to act in a complex interactive manner similar to CD.     

亚甲基四氢叶酸还原酶基因C677T多态与结直肠癌遗传易感性的相关性

目的:探讨亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态与结直肠癌(CRC)遗传易感性的关系.方法:采用TaqMan方法检测CRC 449例与对照672例的MTHFR C677T的基因型分布及差异.以非条件Logistic回归法计算表示相对危险度的比值比(OR)及其95%可信区间(CI).OR值均经性别、年龄、吸烟、饮酒、体质量指数和一级亲属CRC家族史等因素校正.结果:CRC组677T等位基因频率显著低于对照组,其为CRC发生的保护因素(OR:0.70,95%CI:0.58-0.83,P<0.01).与CC纯合子相比,CT杂合子的CRC风险显著降低至0.73倍(95%CI:0.56-0.95,P<0.05),而TT纯合子的CRC风险进一步降至0.47倍(95%CI:0.33-0.68,P<0.01).在非饮酒人群中,C677T的CRC风险保护效应略有增强;而在饮酒人群中,CT和TT基因型携带者的CRC发病风险虽仍低于CC基因型携带者,但差异无统计学意义.在CRC人群中,荷大肿瘤(最大直径>4cm)者携带TT基因型的比例高于荷小肿瘤者(16.3% vs 8.3%,P<0.05);荷黏液腺癌者携带TT基因型的比例高于荷乳头状腺癌及管状腺癌者(22.2% vs 17.1%,10.3%,P=0.084).结论:MTHFR C677T降低CRC发病风险,饮酒可能削弱该多态的CRC风险保护效应.TT基因型可能与CRC肿瘤进展有关.     

TIM-3-574G>T基因多态性与中国汉族人群支气管哮喘的相关性分析

目的采用Meta分析评价T细胞免疫球蛋白黏蛋白域蛋白-3(TIM-3)-574 G>T(rs10515746)基因多态性与中国汉族人群支气管哮喘易感性的关系。 方法检索中外文献数据库中TIM-3-574 G>T基因多态性与中国汉族人群支气管哮喘易感性关系的病例对照研究，末次检索时间为2017年12月20日。采用RevMan 5.0对TIM-3-574 G>T基因多态性与哮喘易感的显性模型OR值进行合并、敏感性分析和亚组分析，以及采用Stata对纳入文献的发表偏倚情况进行评估。 结果共纳入5篇文献，其中病例组患者1 241例，对照组患者1 005例。Meta分析显示中国汉族人中TIM-3-574 G>T基因上突变型GT者的支气管哮喘发病风险较野生型纯合子GG者增加3.06倍(OR＝4.06，95%CI：2.34，7.05)，携带突变基因T者患支气管哮喘的风险比携带野生型G基因者增加3.31倍(OR＝4.31，95%CI：2.50，7.43)。亚组分析显示携带GT基因型的成人和儿童患病风险均较纯合子GG高(儿童组：OR＝4.07，95%CI：1.62，10.20；成人组：OR＝3.09，95%CI：1.40，6.85)。 结论T细胞免疫球蛋白黏蛋白域蛋白-3-574 G>T基因多态性与中国汉族人群支气管哮喘易感性有密切相关，突变T基因携带者患支气管哮喘的风险更高。     

Null genotype of glutathione S-transferase Tl contributes to colorectal cancer risk in the Asian population: a meta-analysis

Background and Aim: Previous studies investigating the association between the glutathione S‐transferase Tl (GSTT1) null genotype and colorectal cancer (CRC) risk in the Asian population have reported controversial results. Thus, a meta‐analysis was performed to clarify the effect of the GSTT1 null genotype on CRC risk in the Asian population. Methods: A comprehensive study was conducted, and 12 case‐control studies were finally included, involving a total of 4517 CRC cases and 6607 controls. Subgroup analyses were performed by the sample size. Results: A meta‐analysis of all 12 studies showed that the GSTT1 null genotype was significantly associated with an increased CRC risk in the Asian population (odds ratio [OR] = 1.10, 95% confidence interval [CI] = 1.02–1.19, the P‐value of the OR [P_OR] = 0.02, the value of the heterogeneity analysis [I²] = 42%). A more obvious association was observed after the heterogeneity was eliminated by excluding one study (OR = 1.15, 95% CI: 1.06–1.25, P_OR = 0.001, I² = 0%). This association was further identified by both subgroup analyses and a sensitivity analysis. Conclusions: This meta‐analysis suggests that the GSTT1 null genotype contributes to an increased colorectal cancer risk in the Asian population.