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.     

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.     

DNA Methylation of NDRG2 in Gastric Cancer and Its Clinical Significance

Background

Gastric cancer is one of the most common digestive malignancies worldwide. N-myc downstream-regulated gene 2 (NDRG2) is a differentiation-related gene that is considered to be a metastasis suppressor gene. In this study, we examined the expression and DNA methylation of NDRG2 in gastric cancer cell lines and tissues, as well as its clinical significance.

Methods

Six gastric cancer cell lines and 42 paired normal and gastric cancer tissue samples were used to assess NDRG2 mRNA expression using RT-PCR. NDRG2 DNA methylation status was evaluated by methylation-specific PCR (MSP) in gastric cancer cell lines and tissues. The suppression of NDRG2 in BGC823 cells by siRNA transfection was utilized to detect the role of NDRG2 in gastric cancer progression.

Results

NDRG2 mRNA was down-regulated in gastric cancer cell lines and tissues, and its expression was just related to lymph node metastasis (p = 0.032). MSP showed methylation of NDRG2 in 54.0 % (47/87) of primary gastric cancer specimens and in 20.0 % (16/80) of corresponding nonmalignant gastric tissues. NDRG2 methylation was related to depth of tumor invasion, Borrmann classification and TNM stage (p < 0.05). Upon treatment with 5-aza-2′-deoxycytidine and trichostatin A, NDRG2 expression was upregulated in HGC27 cells, and demethylation of the highly metastatic cell line, MKN45, inhibited cell invasion. Furthermore, the suppression of NDRG2 by siRNA transfection enhanced BGC823 cells invasion.

Conclusions

Our results suggest that the aberrant methylation of NDRG2 may be mainly responsible for its downregulation in gastric cancer, and may play an important role in the metastasis of gastric cancer.     

Association between promoters polymorphisms of matrix metalloproteinases and risk of digestive cancers: a meta-analysis

Purpose

A variety of studies have been performed to elucidate the polymorphisms in promoter regions of matrix metalloproteinases (MMPs) associated with the risk of digestive cancers, and yet, results remain conflicting and heterogeneous. Thus, we undertook a systematic meta-analysis to determine the genetic susceptibility of MMPs to digestive cancers.

Methods

A computerized literature search was conducted in databases of PubMed, Embase, and ISI Web of Knowledge till October 2012 for any MMP genetic association study in oral squamous, gastric, esophageal, and colorectal carcinomas. Odds ratios (OR) and 95 % confidence interval (CI) were estimated for each gene under dominant and recessive models, and the heterogeneity between studies was assessed using Q test and I ² value. Overall and subgroup analysis according to anatomical sites and ethnicity was carried out. Statistical analysis was performed with Review Manager 5.0.

Results

A total of 40 eligible publications with 68 comparisons were included in this study. For MMP1 nt-1607, individuals with 2G state could increase risk of digestive cancers in total analysis (dominant: OR = 1.31, 95 % CI = 1.16–1.48, P < 0.00001; recessive: OR = 1.29, 95 % CI = 1.11–1.50, P = 0.0009). In the subgroup of tumor sites, significant associations were also observed in esophageal cancer and colorectal cancer under both genetic models. For MMP2 nt-1306, CT or TT carriers performed significant protection against digestive cancer in the dominant model (OR = 0.69, 95 % CI = 0.55–0.85, P = 0.0007) of the overall. In the subgroup analysis, significant association was found in esophageal cancer, with borderline effects in gastric cancer and oral squamous cell carcinoma. For MMP7 ?181 A/G, significant association was observed under two genetic models in the overall (dominant: OR = 1.26, 95 % CI = 1.10–1.43, P = 0.0009; recessive: OR = 1.33, 95 % CI = 1.11–1.60, P = 0.002) and in the individual cancer subgroup of esophageal cancer and gastric cancer. For MMP9 ?1,562 C/T, a borderline effect was found with digestive cancers in the total and stratified analysis of the colorectal cancer under dominant model. No association was observed in either the overall or subgroup analysis for MMP3 ?1,171 5A/6A.

Conclusions

Our meta-analysis demonstrated the fact that polymorphisms in promoter regions of MMP genes might be related to the susceptibility of digestive cancers, with cancer development for MMP1 and MMP7, and a protection against cancer for MMP2 and MMP9. Further evidences with adequate sample sizes need to be conducted.     

Is Colonoscopic Screening Necessary for Patients with Gastric Adenoma or Cancer?

Background

Since colorectal adenoma or cancer is commonly associated with gastric adenoma or cancer, early colorectal adenoma detection can affect the survival of gastric adenoma or cancer patients.

Aims

The purpose here was to investigate the colorectal adenoma or cancer prevalence and evaluate the necessity for screening colonoscopy in gastric adenoma or cancer patients.

Patients and methods

From September 2005 through August 2010, 857 patients younger than 70 years who had gastric adenoma or cancer were enrolled. Healthy age- and sex-matched controls were selected from the general screening population. The prevalence and risk of colorectal adenoma or cancer were compared between the participants and the controls.

Results

Data from 416 patients in the gastric neoplasm group (123 with gastric adenoma and 293 with gastric cancer) and 416 healthy control group participants were included in the statistical analysis. The presence of gastric adenoma or cancer was an independent risk factor for colorectal neoplasm (OR = 1.348, 95 % CI = 1.001–1.815). Patients with diffuse type gastric cancer had a lower prevalence of colorectal adenoma or cancer than those with gastric adenoma or intestinal type cancer. In gastric cancer patients younger than 50 years, intestinal type histology was significantly associated with colorectal adenoma or cancer (OR = 3.838, 95 % CI = 1.077–13.677).

Conclusions

The colorectal adenoma or cancer risk was significantly increased in patients with gastric adenoma or cancer. Therefore, screening colonoscopy should be considered for gastric adenoma or cancer patients including young patients, in the case of intestinal type gastric cancer.     

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.     

Low Prevalence of Microsatellite Instability in Interval Gastric Cancers

Background and Aim

Esophagogastroduodenoscopy (EGD) is recommended at 2-year intervals in countries with a high prevalence of gastric cancer. The aim of this study was to determine whether interval gastric cancers that develop within 2 years of a previous complete screening are associated with microsatellite instability (MSI).

Methods

Newly diagnosed gastric cancer patients who had undergone gastrectomy were included. Of these 459 patients, 177 were classified as interval gastric cancer since they were diagnosed within 2 years of a previous EGD. Noninterval gastric cancer patients were subclassified into 65 patients who underwent previous EGD between the past 2 and 10 years and 217 patients without EGD during the last 10 years. Analysis for MSI was conducted using two mononucleotide and three dinucleotide markers.

Results

MSI was found more frequently in noninterval gastric cancers than in interval gastric cancers (p = 0.009). Interval gastric cancers were associated with a higher prevalence of early gastric cancer (p = 0.006), smaller size (p < 0.001), and lower TNM stages (p = 0.006). On logistic regression analysis, noninterval gastric cancers were related to MSI (p = 0.010) and larger size (≥4 cm) (p = 0.009). Subjects with interval gastric cancer showed better survival than those with noninterval gastric cancer (p = 0.006).

Conclusions

During a 2-year screening interval, noninterval gastric cancers tend to be larger, more advanced, and associated with MSI. Biannual EGD screening is effective for detecting small gastric cancers at an early stage, but is not useful in detecting gastric cancers with MSI.     

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.     

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.     

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.     

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.     

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.     

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.     

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.     

Disease severity and treatment requirements in familial inflammatory bowel disease

Purpose

Several studies demonstrate an increased prevalence and concordance of inflammatory bowel disease among the relatives of patients. Other studies suggest that genetic influence is over-estimated. The aims of this study are to evaluate the phenotypic expression and the treatment requirements in familial inflammatory bowel disease, to study the relationship between number of relatives and degree of kinship with disease severity and to quantify the impact of family aggregation compared to other environmental factors.

Methods

Observational analytical study of 1211 patients followed in our unit. We analyzed, according to the existence of familial association, number and degree of consanguinity, the phenotypic expression, complications, extraintestinal manifestations, treatment requirements, and mortality. A multivariable analysis considering smoking habits and non-steroidal-anti-inflammatory drugs was performed.

Results

14.2% of patients had relatives affected. Median age at diagnosis tended to be lower in the familial group, 32 vs 29, p = 0.07. In familial ulcerative colitis, there was a higher proportion of extraintestinal manifestations: peripheral arthropathy (OR = 2.3, p = 0.015) and erythema nodosum (OR = 7.6, p = 0.001). In familial Crohn’s disease, there were higher treatment requirements: immunomodulators (OR = 1.8, p = 0.029); biologics (OR = 1.9, p = 0.011); and surgery (OR = 1.7, p = 0.044). The abdominal abscess increased with the number of relatives affected: 5.1% (sporadic), 7.0% (one), and 14.3% (two or more), p=0.039. These associations were maintained in the multivariate analysis.

Conclusions

Familial aggregation is considered a risk factor for more aggressive disease and higher treatment requirements, a tendency for earlier onset, more abdominal abscess, and extraintestinal manifestations, remaining a risk factor analyzing the influence of some environmental factors.

     

Clinico-epigenetic combination including quantitative methylation value of DKK3 augments survival prediction of the patient with cervical cancer

Purpose

DKK3 is a target of methylation in various cancers and has been studied by a non-quantitative method. We assessed the quantitative methylation levels of DKK3 in cervical carcinoma, determined the potential clinical correlations, and tested whether the combination of clinical and epigenetic factors augmented the prediction power of prognosis.

Methods

Sixty-two patients with cervical squamous cell carcinoma were included in this study. Quantitative methylation levels were evaluated by pyrosequencing. Clinical and pathologic findings were obtained from medical records. Survival data were analyzed using Kaplan–Meier estimates and compared with the log-rank test. The best clinico-epigenetic combinations were found using the Cox proportional hazard model.

Results

Four of five CpG positions of DKK3 were strongly methylated in cervical carcinoma compared to normal controls (p = 0.0048). The methylation in positions 1 and/or 2 were stronger in patients with higher serum levels of the SCC tumor marker and/or larger tumors (p = 0.01). The patients with a methylation level ≥26.3 % at position 1 had a lower survival rate than the patients with methylation levels at position 1 that were <26.3 % (p = 0.03). The combination of methylation level of position 1, position 3, age, parametrial invasion, and lymphovascular space invasion (LVSI) have a significant correlation with survival (p = 0.0006). Recurrence was significantly related to the combination of methylation level of position 2, position 3, age, parametrium, and LVSI (p = 0.0041).

Conclusions

DKK3 methylation is unfavorable to prognosis. This study defined a threshold level of methylation associated with recurrence-free survival and, furthermore, identified novel clinico-epigenetic combinations predicting disease survival or recurrence.     

Increased Expression of Cellular Repressor of E1A-Stimulated Gene (CREG) in Gastric Cancer Patients: A Mechanism of Proliferation and Metastasis in Cancer

Background

The cellular repressor of E1A-stimulated genes (CREG), a secreted glycoprotein, has been studied with human embryonic carcinoma cells, vascular smooth muscle cells, and NIH3T3 fibroblasts. However, its relationship to tumor cell proliferation and metastasis has not been examined in human gastric cancers (GC) until now.

Aim

To investigate the expression of CREG in GC and its association with GC cell proliferation and metastasis.

Methods

Forty-two cases of GCs, matched normal gastric tissues, and the human gastric cancer cell lines BGC-823, SGC-7901, MKN45, normal gastric mucosa cell line GES, and HUVEC cell line ECV304 were used to analyze CREG expression at the level of mRNA and protein. The expression of CREG was then further examined by immunohistochemistry in 42 GC tissues, and the correlation between the level of CREG and the pathological and clinical data was evaluated. Finally, we down-regulated the expression of CREG in GC cells with specific siRNA, and assessed the role of CREG in the proliferation and metastasis/invasion of the GC cell line.

Results

The level of CREG was found to be higher in malignant GC tissues and cells compared to adjacent normal tissues and normal gastric cells (p < 0.001). Additionally, the expression levels of CREG were positively correlated with tumor clinical stage (p = 0.001), tumor metastasis (p < 0.001), and stages of tumor infiltration (p = 0.019). Furthermore, by using siRNA, we found that the down-regulated expression of CREG inhibited the proliferation of GC cells (p < 0.05), and migration of both GC cells (p = 0.001).

Conclusions

Our data suggest that CREG plays an important role in gastric cancer cell proliferation and metastasis and that CREG may be a potential therapeutic target for GC.     

The Association Between TP53 Arg72Pro Polymorphism and Lung Cancer Susceptibility: Evidence from 30,038 Subjects

Background

The TP53 codon 72 polymorphism has been associated with the individual susceptibility to lung cancer. However, the association remains uncertain and varies with ethnicity, smoking status, cancer histology, and stage.

Methods

We performed a meta-analysis to evaluate the relationship between TP53 Arg72Pro polymorphism and lung cancer susceptibility basing on 15,647 lung cancer patients and 14,391 controls from 36 published literatures. We also performed stratified analysis in populations of different ethnicities, smoking statuses, lung cancer stages, and histological types.

Results

The analysis showed a significantly increased lung cancer susceptibility among Pro allele carriers (P < 0.001, odds ratio (OR) = 1.14, 95 % confidence interval (CI) = 1.1–1.19), especially for smokers (P < 0.001, OR = 1.29, 95 % CI = 1.12–1.47). Stratified analysis indicated that Pro72 elevates lung cancer susceptibility in Asians, while it has no effect on lung cancer risk of Caucasians. Moreover, Pro carriers present an increased risk of developing squamous cell carcinoma and adenocarcinoma, instead of large cell carcinoma and small cell carcinoma. Interestingly, patients with the Pro allele seemed to be diagnosed with lung cancer at the early stages (stage I–II, P = 0.008, OR = 1.2, 95 % CI = 1.05–1.37).

Conclusions

Our results suggest that the Pro allele acts as a risk factor for development of lung cancer, especially for smokers and Asians.     

Association of CYP1B1 Leu432Val Polymorphism and Lung Cancer Risk: An Updated Meta-Analysis

Background

Cytochrome P4501B1 (CYP1B1) a phase I enzyme, is involved in the activation of a broad spectrum of procarcinogens. Impacts on the catalytic activity of the CYP1B1 enzyme, as well as an association of the Leu432Val polymorphism with the risk of lung cancer, have been described; however, the results remain controversial.

Methods

We conducted a meta-analysis of all available studies to clarify the effects of the Leu432Val polymorphism on lung cancer risks basing on 2,543 lung cancer cases and 3,304 controls from ten separate comparisons. We also performed subgroup analyses by ethnicity (categorized as Caucasian, Asian and African-American), gender, smoking status ,and histological type. A pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated to estimate the strength of the association.

Results

A significantly increased risk was found in our meta-analysis in the overall population (Val/Val vs. Leu/Leu: OR = 1.371, 95 % CI 1.137–1.652, P = 0.001). In subgroup analysis, significant associations with lung cancer susceptibility were also found in Caucasians (Val/Val vs. Leu/Leu: OR = 1.312, 95 % CI 1.075–1.602, P = 0.008), females (Val/Val vs. Leu/Leu: OR = 1.472, 95 % CI 1.097–1.976, P = 0.010), and smokers (dominant model Leu/Val + Val/Val vs. Leu/Leu: OR = 1.257, 95 % CI 1.016–1.554, P = 0.035). Null results were noted in the subgroup analysis by histological type under different genetic models.

Conclusions

Our results suggest that the CYP1B1 Leu432Val polymorphism acts as a risk factor for the carcinogenesis of lung cancer.     

TNF-β +252 A>G polymorphism and susceptibility to cancer

Objective

Tumor necrosis factor-β (TNF-β) plays important roles in mediating cancer development. Many studies have argued possible associations of TNF-β +252 A>G polymorphism with different cancers. However, association between this most frequently studied polymorphism and susceptibility to cancer still remains controversial and ambiguous. The aim of this study is to determine the relationship of TNF-β +252 A>G polymorphism with cancer through meta-analysis.

Methods

Electronic searches of several databases were conducted for all publications on the associations between this variant and cancer through October 2011. Odds ratios (ORs) with 95 % confidence intervals (95 % CIs) were used to access the strength of this association in random-effect model.

Results

Thirty-three studies with 14,435 cancer patients and 10,583 healthy controls were included. In this meta-analysis, we detected statistically significant connections between this polymorphism and cancer risks [GG + GA vs. AA: OR = 1.24, 95 % CI = 1.02–1.51; GG vs. AA: OR = 1.43, 95 % CI = 1.05–1.95; G vs. A: OR = 1.28, 95 % CI = 1.28 (1.09–1.50)] in the overall ethnic population. Meanwhile, we detected significant associations in Asian population (GG + GA vs. AA), other population (GG vs. GA + AA), and Caucasian population (GG vs. AA, G vs. A) with the OR values being 1.21 (1.04–1.40), 1.64 (1.35–1.99), 1.65 (1.02, 2.65), and 1.39 (1.09–1.75), respectively.

Conclusions

TNF-β +252 A>G polymorphism is positively associated with susceptibility to cancer. However, this study also suggests that more studies should be conducted to further confirm the associations between this variant and specific types of cancers.