Association between genetic variants in pre-miRNA and colorectal cancer risk in a Chinese population

Introduction

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA expression levels or processing and then contribute to the susceptibility of cancer development. We hypothesized that SNPs in pre-miRNAs may be associated with the risk of colorectal cancer (CRC).

Materials and methods

We genotyped four common polymorphisms (i.e., rs11614913, rs3746444, rs2910164, and rs2292832) in pre-miRNAs of 353 CRC patients and 540 healthy controls to investigate the association between the SNPs and the risk of CRC using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) assay.

Results

The rs11614913 CT, TT genotypes, and T allele were associated with an increased risk of CRC compared with the CC genotype and C allele (CT vs. CC: OR = 7.34, 95 % CI 3.76–14.34; TT vs. CC: OR = 13.66, 95 % CI 6.76–27.6; T vs. C: OR = 1.99, 95 % CI 1.63–2.42, respectively). Interestingly, using the rs2910164 GG genotype as a reference, the rs2910164 GC genotype was associated with an increased risk of CRC (OR = 1.49, 95 % CI 1.02–2.18), whereas the rs2910164 CC genotype was associated with a decreased risk of CRC (OR = 0.58, 95 % CI 0.37–0.93). When compared with the rs2910164G allele, rs2910164 C allele was associated with a reduced risk of CRC (OR = 0.80, 95 % CI 0.66–0.97, p = 0.02).

Conclusion

These findings suggest that rs11614913 and rs2910164 polymorphisms may be associated with the etiology of CRC.     

Polymorphisms in DNA repair genes XRCC1, XRCC3 and XPD, and colorectal cancer risk: a case–control study in an Indian population

Purpose

Genetic polymorphisms in DNA repair genes may influence variations in individual DNA repair capacity, which could be associated with the development of cancer. We detected the distributions of three single-nucleotide polymorphisms (XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln) in DNA repair genes, and assessed the associations of these genetic polymorphisms with colon and rectal cancer susceptibility as well as evaluated the interactions of gene–gene and gene–environment in a case–control study of an Indian population.

Methods

This case–control study was conducted with 302 cases (including 59 colon and 243 rectal cancer patients) and 291 cancer-free healthy controls. Genotypes were determined by PCR–RLFP assays. The effects [odds ratios (ORs) and 95% confidence intervals (95% CIs)] of genetic polymorphisms on colorectal cancer were estimated using unconditional logistic regression.

Results

The XRCC1 399Gln allele was found to be associated with a significantly increased rectal cancer risk among men (OR = 1.65, 95% CI 1.04–2.64). Whereas the XRCC3 241Met allele showed a protective tendency against rectal cancer (OR = 0.68, 95% CI 0.46–1.02) for both men and women. Furthermore, a combination of the XRCC1 399Gln allele with XRCC3 Thr/Thr genotype and the XPD 751Gln allele demonstrated the highest rectal cancer risk (OR = 3.52, 95% CI 1.43–9.44).

Conclusions

The combined effects of putative risk alleles/genotypes for different DNA repair pathways may strengthen the susceptibility to rectal cancer.     

A meta-analysis of the relation of polymorphism at sites −1082 and −592 of the IL-10 gene promoter with susceptibility and clearance to persistent hepatitis B virus infection in the Chinese population

Background

Up to now, many publications about the Chinese population have evaluated the correlation between interleukin-10 (IL-10) ?1082 and ?592 polymorphisms and persistent hepatitis B virus (HBV) infection. However, the results remain inconclusive. In order to resolve this conflict, a meta-analysis was performed.

Methods

Seven studies were included and dichotomous data are presented as the odds ratio (OR) with a 95% confidence interval (CI).

Results

The results of our study suggest that carriers of the IL-10 ?592A allele were more likely to clear HBV spontaneously in the Chinese pooled population (A vs. C: OR = 0.799, 95% CI = 0.678–0.941, P = 0.007; AC vs. AA: OR = 1.343, 95% CI = 1.017–1.684, P = 0.011; AA vs. AC + CC: OR = 0.736, 95% CI = 0.594–0.912; AA + AC vs. CC: OR = 0.588, 95% CI = 0.408–0.848, P = 0.004) and the IL-10 ?1082A allele was associated with significantly reduced persistent HBV infection risk in Chinese (A vs. G: OR = 0.701, 95% CI = 0.494–0.996, P = 0.047; AA vs. GG + GA: OR = 0.684, 95% CI = 0.476–0.982, P = 0.040).

Conclusions

Persistent HBV infection susceptibility is associated with the gene polymorphism IL-10 ?1082GA in the Chinese population and the clearance of HBV is associated with the gene polymorphism IL-10 ?592CA in the Chinese population.     

Association between survivin -31G>C polymorphism and cancer risk: meta-analysis of 29 studies

Purpose

A growing body of evidence has shown the possible relevance of survivin -31G>C (rs9904341) promoter polymorphism to the genetic susceptibility of cancer. Because of the lack of available conclusive data, we performed a meta-analysis of all relevant available studies to derive a more precise estimation of the relationship.

Methods

A comprehensive literature search of Medline electronic database was conducted to collect relevant studies until August 18, 2013. References of the retrieved articles were also screened. The extracted data were statistically analyzed, and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the association strength using Stata version 11.2 software.

Results

A total of 29 studies with 7,473 cancer cases and 9,086 controls were included in the meta-analysis. Overall, the pooled analysis revealed that suvivin -31G>C polymorphism was significantly associated with increased cancer risk under multiple genetic models (CC vs. GG: OR = 1.37, 95 % CI 1.06–1.76; CC vs. CG: OR = 1.27, 95 % CI = 1.10–1.46; CC vs. CG + GG: OR = 1.31, 95 % CI = 1.10–1.57). In subgroup analysis with different cancer types, the -31G>C polymorphism significantly increased the risk of colorectal, gastric, and urothelial cancers, while this SNP remarkably decreased the susceptibility to hepatocellular carcinoma. Further stratification analysis by ethnicity showed an increasing cancer risk in the Asian population (CC vs. GG: OR = 1.61, 95 % CI 1.17–2.21; CC vs. CG: OR = 1.31, 95 % CI 1.12–1.53; CC vs. CG + GG: OR = 1.43, 95 % CI 1.16–1.77) but not in Europeans.

Conclusions

The survivin -31G>C polymorphism is associated with elevated cancer risk, especially among colorectal, gastric, and urothelial cancers and Asian populations.     

Assessment of the XPC (A2920C), XPF (T30028C), TP53 (Arg72Pro) and GSTP1 (Ile105Val) polymorphisms in the risk of cutaneous melanoma

Purpose

We examined the influence of XPC A2920C, XPF T30028C, TP53 Arg72Pro and GSTP1 Ile105Val polymorphisms in the risk of cutaneous melanoma (CM).

Methods

DNA from 146 CM patients and 146 controls was analysed by polymerase chain reaction (PCR)—restriction fragment length polymorphism (RFLP).

Results

The frequencies of XPC CC (15.1 vs. 6.9 %, P = 0.02), TP53 ArgArg (59.6 vs. 45.9 %, P = 0.02), XPC CC plus TP53 ArgArg (19.7 vs. 5.2 %, P = 0.01) and TP53 ArgArg plus GSTP1 IleIle (50.7 vs. 35.6 %, P = 0.03) genotypes were higher in patients than in controls. Carriers of the respective genotypes were under a 2.51 (95 % CI: 1.13–5.55), 1.76 (95 % CI: 1.09–2.83), 4.52 (95 % CI: 1.35–15.16), and 2.01 (95 % CI: 1.04–3.90)-fold increased risks for CM than others, respectively. An excess of TP53 ArgArg genotype was seen in patients with excessive sun exposure compared to patients with standard sun exposure (69.2 vs. 44.1 %, P = 0.02) and also compared to controls (69.2 vs. 45.9 %, P = 0.002). Individuals with TP53 ArgArg genotype and highly exposed to sunlight had 2.65 (95 % CI: 1.42–4.92)-fold increased risk for CM than others. XPC CC (27.8 vs. 10.4 %, P = 0.02) and the GSTP1 IleIle (58.3 vs. 36.8 %, P = 0.04) genotypes were more common in patients with advanced tumours than in patients with localized tumours and were also more common in these patients than in controls (27.8 vs. 6.9 %, P = 0.001; 58.3 vs. 37.0 %, P = 0.02, respectively). Individuals with the respective genotypes had 5.23 (95 % CI: 1.97–13.82)-fold and 2.38 (95 % CI: 1.13–5.01)-fold increased risks for advanced tumour than others, respectively.

Conclusion

Our data suggest that inherited abnormalities of XPC, XPF, TP53 and GSTP1 pathways of the DNA repair, apoptosis and metabolism of reactive oxygen species are important determinants of CM in individuals from south-eastern Brazil.     

XRCC1 Arg399Gln, Arg194Trp, and Arg280His Polymorphisms in Esophageal Cancer Risk: A Meta-Analysis

Background

The X-ray repair cross-complementation group 1 (XRCC1) protein plays an important role in base excision repair.

Aim

To elucidate the role of XRCC1 Arg399Gln, Arg194Trp and Arg280His genotypes in esophageal cancer risk, all available studies were considered in the present meta-analysis.

Methods

Eligible studies were identified by searching several electronic databases for relevant reports published before June 2012.

Results

According to the inclusion criteria and exclusion criteria, a total of 21 eligible studies were included in the pooled analyses. Among the 21 studies, 18 focused on Arg399Gln polymorphism, 11 described the Arg194Trp, and 4 articles investigated on Arg280His. Our analysis suggested that there was no evidence of significant association between XRCC1 Arg399Gln polymorphism and esophageal cancer risk in any genetic model. In the stratified analysis by ethnicity for Arg399Gln polymorphism and esophageal cancer, the results showed that Arg399Gln polymorphism was not associated with esophageal cancer risk. Only 4 studies analyzed the relationship between XRCC1 Arg280His polymorphism and the risk of esophageal cancer. The Arg/His and His/His genotypes were not significantly associated with increased risk of EC. A similar negative association was maintained in dominant and recessive models. However, for XRCC1 Arg194Trp polymorphism, our study showed individuals carrying the variant genotype Trp/Trp had a significant increased risk of esophageal cancer (OR = 1.295, 95 % CI 1.053–1.591, P = 0.014). In addition, increased associations were found in recessive model (OR = 1.332, 95 % CI 1.093–1.624, P = 0.005).

Conclusions

Our meta-analysis suggested that Arg194Trp Trp allele might act as a risk allele in its association with esophageal cancer.     

Familial clustering of hepatocellular carcinoma in HBsAg-positive patients in the United States

Purpose

The impact of familial clustering of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV)-infected persons in a low HBV endemic area was investigated.

Methods

Four hundred thirteen HBsAg-positive patients, 173 with HCC and 240 without HCC, were subgrouped into those with or without a family history of HCC and analyzed for risk factors associated with HCC development. In families with HCC clustering, the ages of HCC onset in parents and siblings were compared.

Results

Forty-four of 173 (25.4 %) HCC patients, all of Asian descent, had 82 other blood relatives with HCC. Of these, 69 (84.1 %) were first-degree relatives. Compared to HCC patients without HCC family history, male HCC patients with family history developed HCC at a younger age than either their mothers or fathers with HCC (45.2 ± 10.3 years vs. 63.0 ± 6.8 years, p < 0.001 and 41.2 ± 14.8 years vs. 60.5 ± 5.5 years, p = 0.001, respectively); however, this was not observed in female HCC patients. In mothers of index HCC cases, 22/26 (84.6 %) tested were HBsAg positive and 14 (63.6 %) had HCC; in fathers, 11/21 (52.4 %) tested were HBsAg positive and 10 (90.9 %) had HCC. By multivariate analysis, independent risk factors for HCC development included family history (OR = 2.58, p = 0.05), male gender (OR = 3.23, p = 0.03), cirrhosis (OR = 2.4, p = 0.04), Child-Pugh classification (OR = 7.62, p = 0.004), AFP per log₁₀ increase (OR = 1.68, p = 0.01), precore mutation (OR = 3.77, p = 0.003), and basal core promoter mutation (OR = 8.33, p < 0.001).

Conclusions

HBsAg-positive male HCC patients presented at a younger age than their parents with HCC. In adult patients with an HCC family history, HCC surveillance should begin at the time of the initial clinic encounter.     

Cholecystectomy and Clinical Presentations of Gastroparesis

Background

Many patients with gastroparesis have had their gallbladders removed.

Aim

To determine if clinical presentations of patients with gastroparesis differ in those with prior cholecystectomy compared to patients who have not had their gallbladder removed.

Methods

Gastroparetic patients were prospectively enrolled in the NIDDK Gastroparesis Registry. Detailed history and physical examinations were performed; patients filled out questionnaires including patient assessment of GI symptoms.

Results

Of 391 subjects with diabetic or idiopathic gastroparesis (IG), 142 (36 %) had a prior cholecystectomy at the time of enrollment. Patients with prior cholecystectomy were more often female, older, married, and overweight or obese. Cholecystectomy had been performed in 27/59 (46 %) of T2DM compared to 19/78 (24 %) T1DM and 96/254 IG (38 %) (p = 0.03). Patients with cholecystectomy had more comorbidities, particularly chronic fatigue syndrome, fibromyalgia, depression, and anxiety. Postcholecystectomy gastroparesis patients had increased health care utilization, and had a worse quality of life. Independent characteristics associated with prior cholecystectomy included insidious onset (OR = 2.06; p = 0.01), more comorbidities (OR = 1.26; p < 0.001), less severe gastric retention (OR(severe) = 0.68; overall p = 0.03) and more severe symptoms of retching (OR = 1.19; p = 0.02) and upper abdominal pain (OR = 1.21; p = 0.02), less severe constipation symptoms (OR = 0.84; p = 0.02), and not classified as having irritable bowel syndrome (OR = 0.51; p = 0.02). Etiology was not independently associated with a prior cholecystectomy.

Conclusions

Symptom profiles in patients with and without cholecystectomy differ: postcholecystectomy gastroparesis patients had more severe upper abdominal pain and retching and less severe constipation. These data suggest that prior cholecystectomy is associated with selected manifestations of gastroparesis.     

Association Between Cyclin D1 Polymorphism with CpG Island Promoter Methylation Status of Tumor Suppressor Genes in Gastric Cancer

Background

CpG island hypermethylation of tumor suppressor genes is highly involved in gastric carcinogenesis, and enhanced cell proliferation could accelerate this process. Cyclin D1 regulates cell cycle function and may play a role in methylation-related carcinogenesis.

Aims

We investigated the association between Cyclin D1 gene G870A polymorphism and the methylation status of tumor suppressor genes in gastric cancer.

Methods

Polymorphisms at G870A in the Cyclin D1 gene were genotyped, and methylation status of the p14, p16, DAP-kinase, and CDH1 genes were determined by methylation-specific-polymerase chain reaction in 139 gastric cancer tissues. CIHM high was defined as three or more methylated CpG islands.

Results

Although no association was found between methylation status and different stages and Lauren’s subtypes, patients with CIHM of DAP-kinase showed significantly worse survival than those without (p = 0.017). In addition, the number of methylated sites was also associated with survival curves (p = 0.0397). The 870G carrier a significantly lower prevalence of CIHM high compared to the AA genotype in advanced-stage gastric cancer (adjusted OR = 0.32, p = 0.047). A weak correlation between the same genotypes and CIHM of p14 were found in the same subtype (adjusted OR = 0.32, p = 0.052). The mean methylation number was significantly lower in G carriers than in AA genotypes in advanced-stage gastric cancer (p = 0.017).

Conclusions

Genetic polymorphism of CCND1 is associated with CIHM status in gastric cancer, especially in the advanced stage, but is independent of clinico-pathological features.     

The effect of systemic antibiotic prophylaxis for cirrhotic patients with peptic ulcer bleeding after endoscopic interventions

Purpose

All previous studies reported the benefit of antibiotic prophylaxis in cirrhotic patients with either a mixture of nonvariceal and variceal bleeding or variceal bleeding alone. Reports on sole peptic ulcers bleeding are lacking. We aimed to assess the effect of antibiotic prophylaxis in cirrhotic patients with peptic ulcer bleeding after endoscopic interventions and the risk factors associated with recurrent bleeding.

Methods

A cross-sectional retrospective chart review study was conducted on 148 cirrhotic patients with acute peptic ulcer hemorrhage who underwent therapeutic endoscopic procedures. Patients who received prophylactic intravenous ceftriaxone were classified as group A (n = 38) and those who did not receive antibiotics were classified as group B (n = 110). The outcomes were prevention of infection, length of hospital stay, time of rebleeding, and death.

Results

More patients suffered from recurrent bleeding and infection in group B than those in group A (28.2 vs. 5.3 %; p = 0.003, and 26.4 vs. 10.5 %; p = 0.043, respectively). The risk factors associated with recurrent bleeding were being male (OR = 3.4; p = 0.024), those with advanced stage of cirrhosis with Child–Pugh’s class C (OR = 3.8; p < 0.001), and those without antibiotic prophylaxis (OR = 8.9; p = 0.003). The observed 30-day survival was virtually identical for both groups (p = 0.279).

Conclusions

Antibiotic prophylaxis in cirrhotic patients after endoscopic interventions for acute peptic ulcer hemorrhage reduced infections and decreased rebleeding. Male gender, cirrhosis Child–Pugh’s class C, and no antibiotic prophylaxis were independent predictors of recurrent bleeding. Further studies should be directed to explore ways to improve the overall outcome of these patients.     

Polymorphisms of Tumor Necrosis Factor-Alpha and Hepatocellular Carcinoma Risk: A HuGE Systematic Review and Meta-Analysis

Background

Studies investigating the associations between tumor necrosis factor-alpha (TNFA) polymorphisms and hepatocellular carcinoma (HCC) risk report conflicting results. We conducted a meta-analysis to assess the association between TNFA gene TNFA-308(G/A), TNFA-238(G/A), TNFA-863(C/A), TNFA-857(C/T), TNFA-1031 (T/C) polymorphisms and HCC susceptibility.

Methods

Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Database. Summary odds ratios (ORs) and 95% confidence intervals (95% CIs) for TNFA polymorphisms and HCC were calculated in a fixed-effects model (the Mantel?CHaenszel method) and a random-effects model (the DerSimonian and Laird method) when appropriate.

Results

This meta-analysis included 17 case?Ccontrol studies, which included 2,357 HCC cases and 3,161 controls. Overall, the variant genotypes AA/AG of -308G/A were associated with a significantly increased HCC risk, when compared with GG genotype (AA vs. GG, OR = 1.97, 95%CI = 1.01?C3.83; AG vs. GG, OR = 1.88, 95%CI = 1.23?C2.88; AA/AG vs. GG, OR = 1.80, 95%CI = 1.19?C2.72). When stratifying for ethnicity, significantly elevated HCC risk was found among Asians. Moreover, similar results were observed between TNFA-238G/A, TNFA-863C/A polymorphisms and HCC risk among Asians (for -238G/A, AG vs. GG OR = 1.63, 95%CI = 1.17?C2.26, AA/AG vs. GG OR = 1.61, 95%CI = 1.16?C2.24; for -863 C/A, AC vs. CC OR = 1.72, 95%CI = 1.03?C2.88, AA/AC vs. CC OR = 1.71, 95%CI = 1.02?C2.86), while no associations were observed between TNFA-857C/T, TNFA-1031T/C polymorphisms and HCC susceptibility.

Conclusions

This meta-analysis shows that TNFA-308G/A, TNFA-238G/A and TNFA-863C/A polymorphisms may be associated with HCC among Asians. TNFA-857C/T and TNFA-1031T/C polymorphisms were not detected to be related to the risk for HCC.     

Angiotensinogen Promoter Polymorphisms Predict Low Diffusing Capacity in U.S. and Spanish IPF Cohorts

Background

Single nucleotide polymorphisms (SNPs) in angiotensinogen (AGT) at positions ?20 and ?6 are associated with increased severity and progression of various fibrotic diseases. Our earlier work demonstrated that the progression of idiopathic pulmonary fibrosis (IPF) was associated with the A-6 allele. This study examined the hypothesis that the homozygous CC genotype at ?20 and the AA genotype at ?6 would confer worse measures of pulmonary function (measured by pulmonary function tests) in IPF.

Methods

Multiple logistic regression analysis was applied to a NIH Lung Tissue Research Consortium cohort and a Spanish cohort, while also adjusting for covariates to determine the effects of these SNPs on measures of pulmonary function.

Results

Analysis demonstrated that the CC genotype at ?20 was strongly associated with reduced diffusing capacity in males in both cohorts (p = 0.0028 for LTRC and p = 0.017 for the Spanish cohort). In females, the AA genotype was significantly associated with lower FVC (p = 0.0082) and V _alv (p = 0.022). In males, the haplotype CA at ?20 and ?6 in AGT was also strongly associated with reduced diffusing capacity in both cohorts.

Conclusions

This study is the first to demonstrate an association of AGT polymorphisms (?20A > C and ?6G > A) with lower measures of pulmonary function in IPF. It is also the first to relate the effect of gender in lung fibrosis with polymorphisms in AGT.     

Backwash Ileitis and the Risk of Colon Neoplasia in Ulcerative Colitis Patients Undergoing Restorative Proctocolectomy

Background

The significance of backwash ileitis (BWI) relating to the risk of colon neoplasia in ulcerative colitis (UC) patients is controversial.

Aim

We investigated the association between BWI and the presence of colon neoplasia in the colectomy specimen.

Methods

From 4,198 UC patients in a prospectively maintained pouch database from 1983 to 2011, patients with extensive colitis and BWI (n = 178) in proctocolectomy were compared with 537 controls [extensive colitis (n = 385) and left-sided colitis (n = 152)] without ileal inflammation.

Results

Colon neoplasia (colon dysplasia and/or colon cancer) was seen in 32 (18 %) patients with BWI in contrast to 45 (11.7 %) with extensive colitis and 13 (8.6 %) with left-sided colitis alone (p = 0.03). Of those with BWI, colon cancer was seen in 10 patients (5.6 %), while low grade and high grade dysplasia were seen in 7 (3.9 %) and 15 (8.4 %) patients respectively. On multivariate analysis, the presence of BWI with extensive colitis [odds ratio (OR) = 3.53; 95 % confidence interval (CI) 1.01–12.30, p = 0.04], presence of primary sclerosing cholangitis (PSC) (OR = 5.79, 95 % CI 1.92–17.40, p = 0.002) and moderate to severe disease activity at UC diagnosis (OR 4.29, 95 % CI 2.06–9.01, p < 0.001) were associated with an increased risk for identifying any colon neoplasia. For colon cancer, the presence of PSC (OR = 11.30, 95 % CI 1.54–80.9, p = 0.01) was the only factor independently associated with an increased risk.

Conclusions

The presence of BWI with extensive colitis was associated with the risk of identifying colon neoplasia but not cancer alone in the proctocolectomy specimen.     

IL28B polymorphisms predict the virological response to standard therapy in patients with chronic hepatitis C virus genotype 4 infection

Background

Genome-wide association studies have recently revealed that several single-nucleotide polymorphisms (SNPs) in the interleukin (IL) 28B genes can predict the sustained virological response (SVR) to pegylated interferon-α2a/b plus ribavirin in hepatitis C virus (HCV)-genotype 1 patients. However, data for patients infected with HCV genotype 4 (HCV-G4) are limited.

Aim

We analyzed the association of IL28B SNPs (hematological, biochemical, virological, and pathological factors) with SVR in the HCV-G4 monoinfected cohort of patients.

Patients and methods

One hundred twenty-nine treatment-naïve HCV-G4 patients undergoing treatment were recruited from three tertiary care centers in Saudi Arabia. Five IL28B SNPs (rs12979860, rs12980275, rs8105790, rs8099917, and rs72486680) were identified by polymerase chain reaction and DNA sequencing. SVR was statistically correlated with various clinical, histopathological, virological, and genetic parameters.

Results

SVR was significantly associated with the CC and AA alleles of rs12979860 (p = 0.008) and rs12980275 (p = 0.004), respectively. Moreover, albumin levels (p = 0.002) and platelet count (p = 0.039) showed significant differences in the SVR and No SVR groups. On multivariate analysis, the CC allele of rs12979860 (OR, 2.89; 95 % CI 1.6–6.2, p = 0.006) and albumin levels (OR, 1.2; 95 % CI 1.1–1.4, p = 0.001) independently predicted SVR.

Conclusions

IL28B polymorphism (CC allele of rs12979860) predicts the sustained response to antiviral therapy in HCV-G4.     

Individual risk assessment in bladder cancer patients based on a multi-marker panel

Purpose

To investigate whether a combined application of urine cytology (CYT) and molecular markers for bladder cancer (BC) can predict tumor aggressiveness.

Methods

The study comprised 2,113 patients who underwent urethrocystoscopy and transurethral resection of the bladder. CYT, fluorescence in situ hybridization (FISH), immunocytology (uCyt+) and nuclear matrix protein 22 test (NMP22-ELISA) were performed. Results of the individual tests and of a multi-marker panel were correlated with pT-stages and tumor grades.

Results

Five hundred and two of 2,113 (23.8 %) patients had BC. False-negative test rates of CYT (p < 0.001), FISH (p = 0.01) and NMP22-ELISA (p = 0.05) were lower in patients with muscle-invasive BC compared with patients with non-muscle-invasive BC. Furthermore, false-negative rates of CYT (p < 0.001), FISH (p = 0.0002) and NMP22-ELISA (p < 0.001) were lower in patients with G3/CIS compared with patients with G1–G2 BC. In patients with evidence of tumor in urethrocystoscopy, the presence of simultaneously positive CYT and NMP22 was associated with a 20-fold risk for G3/CIS (p < 0.0001).

Conclusions

This is the first study investigating the combined use of four urine markers in addition to cystoscopy to predict tumor aggressiveness. Our results indicate that combined application of urine markers as an adjunct to cystoscopy may facilitate identification of patients harboring high-grade tumors.     

Water infusion versus air insufflation for colonoscopy: a meta-analysis of randomized controlled trials

Background

The aim of this meta-analysis was to determine whether water infusion colonoscopy (WIC) is a more effective diagnostic tool than standard air insufflation colonoscopy (AIC).

Methods

All articles pertinent to a comparison of water-related methods and air insufflation to facilitate insertion of the colonoscope were retrieved from PubMed, Web of Science, Embase, and Cochrane databases. Pooling results were derived by using the Review Manager Software. Outcomes were assessed using the weighted mean difference (MD) with 95 % confidence intervals (CI) for continuous variables and the odds ratios (OR) with 95 % CI for dichotomous variables.

Results

Eighteen studies involving 2,797 patients were included. WIC was associated with a significantly higher cecal intubation rate than AIC (OR = 1.90; 95 % CI 1.21–2.99; p = 0.005). The intubation time was similar for the two types of colonoscopy, but in WIC there was a significantly lower visual analog scale score for abdominal pain than in AIC (MD = ?1.30; 95 % CI ?2.03 to ?0.58; p < 0.001) without sacrificing the polyp detection rate (OR = 1.17; 95 % CI 0.78–1.77; p = 0.44). Statistically, the patient’s willingness to repeat colonoscopy was significantly greater for WIC than for AIC (OR = 1.74; 95 % CI 1.14–2.67; p < 0.01). Furthermore, in the subgroup for trainees, the WIC group achieved a higher cecal intubation rate (OR = 1.83; 95 % CI 1.15–2.93; p = 0.01) and a shorter intubation time (MD = ?1.72 min; 95 % CI ?3.34 to ?0.11; p = 0.04) than the AIC group.

Conclusions

In contrast to AIC, WIC improved cecal intubation, alleviated abdominal pain, and increased patients’ willingness to repeat the procedure.     

Association of KIR genotype with susceptibility to HLA-B27-positive ankylosing spondylitis

Objective

Recent studies have explored the role of killer cell immunoglobulin-like receptors (KIRs) in chronic autoimmune diseases. The purpose of this study was to demonstrate whether KIR genes contribute to the pathogenesis of ankylosing spondylitis (AS) in Chinese populations.

Methods

Sixteen KIR genes were genotyped from 60 unrelated patients with AS and 60 HLA-B27-positive matched healthy controls by PCR-SSP. The frequencies of the KIR alleles and genotypes in the AS and control groups were assessed by the χ ² test.

Results

Our results showed that the frequency of the activator receptor KIR3DS1 gene in the AS group was significantly increased compared to the controls (χ ² = 5.263, P = 0.006, OR = 3.059, 95 % CI = 1.357–6.896). Moreover, the frequency of the KIR3DL1/3DS1 genotype was greater in the AS group than in the control group (P = 0.039, OR = 3.059, 95 % CI = 1.357–6.896). In contrast, the frequency of the no KIR3DL1/no 3DS1 genotype was lower in patients with AS compared with the controls (P = 0.032, OR = 0.110, 95 % CI = 0.013–0.911).

Conclusion

KIR3DS1, in addition to HLA-B27, may play an important independent role in the pathogenesis of AS in the Chinese population.     

S100A Expression and Interleukin-10 Polymorphisms Are Associated with Ulcerative Colitis and Diarrhea Predominant Irritable Bowel Syndrome

Background

Both ulcerative colitis (UC) and diarrhea-predominant irritable bowel syndrome (IBS-D) are associated with alterations in enteric serotonin (5-HT) signaling.

Aims

The purpose of this study was to compare the rectal and sigmoid colonic mucosal expression of S100A proteins and functional polymorphisms of the 5-HT transporter (5HTT) and interleukin-10 genes in patients with IBS-D or UC with healthy controls.

Methods

mRNA expression of S100 proteins was measured in sigmoid and rectal biopsies and in rectal epithelium isolated by laser-captured microdissection. Leucocyte DNA was analyzed by PCR-based reaction fragment length polymorphisms and direct sequencing. Clinical symptoms were assessed by the self-rating depression scale and by the gastrointestinal symptom rating scale.

Results

Fifty patients with IBS-D, 56 with UC and 50 healthy controls were studied. Colonic mucosal expression of S100A8 and S100A9 in UC was significantly higher than in IBS or controls and correlated with the UC disease activity index (r = 0.65, p < 0.001). S100A10 expression in the rectal epithelium of the IBS patients was significantly higher (0.643 vs. 0.402, p = 0.01) than in controls and correlated with the SDS scores (r = 0.41, p = 0.002). The frequency of IL10-819 CC genotype was significantly higher in IBS-D (10.7 vs. 0 %, p = 0.047) and UC (16 vs. 0 %, p = 0.007) than that in controls.

Conclusion

Overexpression of S100A10 in the rectum may play a role in IBS as it is involved in modulating 5-HT1B receptors. The IL10-819 CC is a candidate genotype for both IBS and UC in Japanese.     

ADAM33 Gene Polymorphisms are Associated with the Risk of Idiopathic Pulmonary Fibrosis

Background

Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function due to remodeling of the lung, including epithelial mesenchymal transition. ADAM33 is a disintegrin and metalloprotease domain-containing protein, which may be related to lung fibrosis by exerting angiogenesis and remodeling of the lung. Thus, we evaluated the association of single-nucleotide polymorphisms (SNPs) of ADAM33 with the risk of IPF.

Methods

A total of 237 patients with IPF and 183 healthy subjects participated in the present study. Nine polymorphisms were selected. Genotyping was performed by single-base extension. Polymorphisms and haplotypes were analyzed for associations with the risk of IPF using multiple logistic regression models controlling for age, gender, and smoking status as covariates.

Results

All SNPs were in Hardy-Weinberg equilibrium. The minor allele frequency (MAF) of rs628977G>A in intron 21 was significantly lower in subjects with surgical IPF than in normal controls in the recessive model [33.2 vs. 38.0 %, p = 0.02, OR = 0.40 (0.19–0.84)]. When the subjects with clinical IPF were included, the difference in MAF persisted with a p value of 0.03 [OR = 0.50 (0.27–0.94)].

Conclusions

ADAM33 rs628977G>A was marginally associated with a decreased risk of IPF in a recessive model.     

Positive association between circulating 25-hydroxyvitamin D levels and prostate cancer risk: new findings from an updated meta-analysis

Purpose

To investigate and clarify the relationship between circulating 25-hydroxyvitamin D level and prostate cancer risk.

Methods

We conducted the meta-analysis to better evaluate the association. Terms “25-Hydroxyvitamin D”/“vitamin D” and “prostate cancer” were used for literature search.

Results

We identified 21 relevant publications from databases of PubMed and MEDLINE and included 11,941 cases and 13,870 controls in the meta-analysis. Overall studies revealed a significant 17 % elevated risk of prostate cancer for individuals with higher level of 25-hydroxyvitamin D (OR = 1.17, 95 % CI = 1.05–1.30, P  = 0.004), and no publication bias was found in the calculations (P  = 0.629). Subgroup analysis confirmed the association from nested case–control study group, studies from USA group and studies using serum samples group (nested case–control studies: OR = 1.17, 95 % CI = 1.08–1.27, P < 0.001; USA: OR = 1.15, 95 % CI = 1.03–1.29, P = 0.017; serum: OR = 1.20, 95 % CI = 1.01–1.42, P = 0.042); moreover, sensitivity tests also indicated significant results in studies from Europe and studies conducting with plasma samples after exclusion of some influential single study from the analysis, respectively (Europe: OR = 1.21, 95 % CI = 1.04–1.40, P = 0.014; plasma: OR = 1.13, 95 % CI = 1.00–1.27, P = 0.05).

Conclusions

Our meta-analysis, for the first time, suggested significant positive relationship between high level of 25-hydroxyvitamin D and increased risk of prostate cancer, reminding us that more concern should be taken into account during assessing the effect of 25-hydroxyvitamin D.