Current evidence on the relationship between murine double minute 2 T309G polymorphism and esophageal cancer susceptibility

The relationship between murine double minute 2 (MDM2) T309G polymorphism and esophageal cancer risk has been discussed with discrepant results. The aim of our study is to investigate the systematic association between the potentially functional MDM2 T309G polymorphism and esophageal cancer risk. Eligible studies were included through searching the databases of PubMed, EMBASE, and Chinese National Knowledge Infrastructure (up to April 2014). The crude odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. Six published case–control studies, including 1899 cases and 3016 controls, were identified. Overall, our study suggested that MDM2 T309G polymorphism was significantly associated with increased risk of esophageal cancer (TT vs. GG: OR = 0.77, 95% CI = 0.65–0.90, P = 0.002; T vs. G: OR = 0.88, 95% CI = 0.81–0.96, P = 0.002). In subgroup analyses stratified by source of controls, ethnicity, and quality score assessment, respectively, similar results were obtained (TT vs. GG: OR = 0.65, 95% CI = 0.48–0.89, P = 0.007 for hospital‐based studies; T vs. G: OR = 0.90, 95% CI = 0.81–0.99, P = 0.04 for population‐based studies; and T vs. G: OR = 0.85, 95% CI = 0.78–0.93, P = 0.004 for Asians). The results of Begg's test and Egger's test did not suggest publication bias in the studies. Therefore, the MDM2 T309G polymorphism may be significantly associated with increased esophageal cancer risk, especially among Asians.     

Human papillomavirus (HPV) infection and the risk of esophageal squamous cell carcinoma

There is currently no consensus on the relationship between human papillomavirus (HPV) infection and the pathogenic process of esophageal squamous cell carcinoma (ESCC). Therefore, a retrospective study was performed to explore the association between HPV infection and ESCC, where 225 patients with diagnosed ESCC and 224 matched controls were enrolled in the study and stratified according to smoking and alcohol consumption. Enzyme‐linked immunosorbent assay was used to determine seropositivity to HPV by the detection of either IgG or IgM anti‐HPV antibodies. In the non‐smoking and non‐alcohol‐consuming subgroup, the incidence of ESCC of HPV seropositive subjects was similar with that of HPV seronegative subjects (P= 0.737, odds ratio [OR] 1.14, 95% confidence interval [CI] 0.54–2.40). However, in the smoking subgroup, there was a significant difference in the incidence of ESCC between HPV seropositive subjects and HPV seronegative subjects (P= 0.009, OR 2.22, 95% CI 1.22–4.04). In addition, there was a significantly higher association of the development of ESCC in HPV seropositive patients that smoke and drink than those that do not (P < 0.001, OR 10.31, 95% CI 4.04–26.29). Therefore, HPV infection is not an independent risk factor for developing ESCC in the non‐smoking and non‐alcohol‐consuming group. For smokers, however, HPV infection increases the risk of the incidence of ESCC.     

The impact of E‐cadherin expression on the prognosis of esophageal cancer: a meta‐analysis

E‐cadherin is a 120‐KD transmembrane calcium‐dependent cell adhesion protein that has been demonstrated drownregulated in a large amount of invasive tumors. However, its effect on the prognosis of esophageal cancer (EC) remains controversial. All the relevant English articles that reported survival data or clinicopathological parameters were enrolled in this meta‐analysis. A total of 24 studies, including 2691 cases, were included in this study. Twelve studies containing 1669 cases were enrolled to synthesize with hazard ratio (HR) and its 95% confidence interval (CI). The pooled HR for all 12 studies enrolled in this meta‐analysis was 1.33 (95% CI 1.16–1.52; z = 3.99, P = 0.00). When the study measured by enzyme‐linked immunosorbent assay is excluded, the pooled HR‐evaluated E‐cadherin to reduce the expression in EC, and in esophageal squamous cell carcinoma was 1.39 (95% CI 1.22–1.58; z = 5.08, P = 0.00) and 1.38 (95% CI 1.21–1.56; z = 4.87, P = 0.00), respectively. The risk of reduced E‐cadherin expression on poor differentiation degree was 1.636 (95% CI 1.33–2.02). The pooled odds ratio of reduced E‐cadherin expression on deeper tumor invasion, lymph node metastasis, and higher clinical stage were 2.63 (95% CI 1.75–3.94), 1.77 (95% CI 1.06 ?2.97), and 3.39 (95% CI 1.85–6.23). Reduced E‐cadherin expression detected by immunohistochemistry could be a valid prognostic marker in patients with EC, especially in patients with esophageal squamous cell carcinoma. Reduced E‐cadherin expression is significantly associated with poorer differentiation degree.     

PTEN polymorphisms and the risk of esophageal carcinoma and gastric cardiac carcinoma in a high incidence region of China

SUMMARY. PTEN, as a tumor suppressor gene, plays an important role in regulating cell growth, proliferation, and apoptosis. Two common polymorphisms, –9C/G and IVS4 (?/+), may alter susceptibility to the disease. To test the hypothesis that the genetic variations of PTEN play a role in the etiology of esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA), a population‐based case‐control study was conducted in 350 ESCC patients, 257 GCA patients, and 634 healthy controls from a high‐incidence region of Hebei province, China. The PTEN polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism analysis (PCR‐RFLP). The results showed that the family history of upper gastrointestinal cancer (UGIC) significantly increased the risk of developing ESCC and GCA (the age, gender and smoking status adjusted OR = 1.73 and 1.67; 95% CI = 1.29–2.32 and 1.28–2.19, respectively). The overall distribution of the PTEN –9C/G genotype was not significantly different between cancer patients and controls. Compared with the PTEN IVS4‐/? genotype, the IVS4+/+ genotype significantly decreased the risk of ESCC and GCA development, the adjusted OR was 0.64 (95% CI = 0.44–0.94) and 0.63 (95% CI = 0.41–0.98), respectively. Stratification analysis by gender, age, smoking status and family history of UGIC showed that the PTEN IVS4?/+ genotype only reduced the risk of ESCC (adjusted OR = 0.55, 95%CI = 0.34–0.90) among subjects with family history of UGIC. While the IVS4+/+ genotype decreased the susceptibility to both ESCC and GCA (adjusted OR = 0.61 and 0.57, 95% CI = 0.37–0.98 and 0.34–0.98, respectively) among male subjects, the IVS4+/+ genotype only decreased the risk of ESCC development among subjects younger than 55 years (adjusted OR = 0.43, 95% CI = 0.21–0.85). In addition, the haplotype analysis found that the –9C/IVS4– haplotype increased the risk of developing ESCC and GCA (OR = 1.31 and 1.24, 95% CI = 1.08–1.58 and 1.001–1.53). Our results suggested that the PTEN IVS4+/+ homozygote may play a protective role in the development of ESCC and GCA, while the haplotype –9C/IVS4– might be the risk factor of the development of ESCC and GCA in the high incidence region population of Hebei province, China.     

Association of Helicobacter pylori infection with esophageal adenocarcinoma and squamous cell carcinoma: a meta‐analysis

To evaluate the relationship of Helicobacter pylori and cytotoxin‐associated gene A (CagA) positive strains with esophageal neoplasm, including esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), the authors conducted a meta‐analysis using a predefined protocol. PubMed, Web of Science, China biology medical literature database, Wanfang, and China National Knowledge Infrastructure were searched for relevant articles from the first available year to April 8, 2013. The fixed or random effect pooled measure was selected based on heterogeneity among studies, which was evaluated using Q test and the I² of Higgins and Thompson. Metaregression was used to explore the sources of between‐study heterogeneity. Publication bias was analyzed by Begg's funnel plot and Egger's regression test. The association was assessed by odds ratio (OR) with 95% confidence interval (CI). A total of 28 eligible studies were included in the meta‐analysis. There was a significant inverse association between H. pylori infection (pooled OR, 0.57; 95% CI, 0.44–0.73) and EAC; CagA‐positive H. pylori strains were less likely to be associated with EAC compared with CagA‐negative strains (pooled OR, 0.64; 95% CI, 0.52–0.79). However, there was no statistically significant association between H. pylori/CagA‐positive H. pylori strains infection and ESCC, and the pooled ORs were 1.16 (95% CI, 0.83–1.60) and 0.97 (95% CI, 0.79–1.19). But significant associations between CagA‐positive H. pylori strains infection and ESCC risk were found in the stratified analysis of the study location (Asian and non‐Asian), and the summary ORs were 0.74 (95% CI, 0.57–0.97) and 1.41 (95% CI, 1.02–1.94). H. pylori infection and CagA‐positive strains are associated with decreased risk of EAC in the overall population. No significant association was found between H. pylori infection/CagA‐positive strains and ESCC. But CagA‐positive strains might have a positive association with ESCC in non‐Asian population and an inverse association in Asian population.     

Genotypes of CYP1A1, SULT1A1 and SULT1A2 and risk of squamous cell carcinoma of esophagus: outcome of a case–control study from Kashmir,India

Studies on associations of various polymorphism in xenobiotic metabolizing genes with different cancers including esophageal squamous cell carcinoma (ESCC) are mixed and inconclusive. To evaluate the association of CYP1A1*4, SULT1A1*2 and SULT1A2*2 genotypes with ESCC risk and their modifying effects on different risk factors of ESCC, we conducted a case–control study in Kashmir, India, an area with relative high incidence of ESCC. We recruited 404 histopathologically confirmed ESCC cases, and equal number of controls, individually matched for sex, age and district of residence to respective case. Information was obtained on various dietary, lifestyle and environmental factors in face‐to‐face interviews, using a structured questionnaire, from each subject. Genotypes were analyzed by polymerase chain reaction, restriction fragment length polymorphism and direct sequencing. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs). A higher risk was observed in the subjects who harbored variant genotype of CYP1A1*4 (OR = 2.06; 95% CI: 1.28–3.32); and the risk was further enhanced in ever smokers (OR = 3.47; 95% CI: 1.62–7.42), adobe dwellers (OR = 6.71; 95% CI: 3.02–14.89), and biomass fuel users (OR = 5.11; 95% CI: 1.34–19.50). We did not find any significant differences in the polymorphic variants of SULT1A1*2 and SULT1A2*2 between cases and controls. The study indicates that, unlike SULT1A1*2 and SULT1A2*2, the polymorphism of CYP1A1*4 is associated with ESCC risk. However, replicative studies with larger sample size are needed to substantiate our findings.     

Replication of results of genome‐wide association studies on esophageal squamous cell carcinoma susceptibility loci in a Korean population

Two recent genome‐wide association studies have identified that the rs2274223 single‐nucleotide polymorphism inphospholipase C epsilon 1 and the single‐nucleotide polymorphism rs13042395 in C20orf54 are involved in esophageal squamous cell carcinoma (ESCC) in Chinese populations. We hypothesized that genetic polymorphisms of phospholipase C epsilon 1 and C20orf54 are also associated with ESCC in a Korean population. The rs2274223 and rs13042395 genotyping was performed using high‐resolution melting analysis. The rs2274223 GG genotype was significantly associated with an increased risk of ESCC (odds ratio [OR] = 1.86, 95% confidence interval [CI] = 1.08–3.25) compared with the rs2274223 AA genotype. The rs13042395 G allele showed a significantly decreased risk of ESCC in the younger age group (OR = 0.71, 95% CI = 0.52–0.97) and no significant association in the older group (OR = 1.19, 95% CI = 0.87–1.62). We observed that the rs2274223 polymorphism was associated with an increased risk of ESCC in this Korean case–control study and that age may modify the association between the rs13042395 polymorphism and the risk of ESCC.     

Invasive and prognostic significance of pRB in esophageal squamous cell carcinoma: a meta‐analysis

This paper investigates the association between protein retinoblastoma (pRB) loss and the T,N stage and prognosis in esophageal squamous cell carcinomas (ESCCs) using meta‐analysis. We conducted a meta‐analysis of 16 studies, comprising 1,117 patients to clarify this issue. All the studies searched by the electronic literature PubMed and http://www.KJEBM.com , which had been published during the period from January 1996 to January 2012 according to the inclusion criteria. Summary odds ratios (OR) were calculated using fixed or random‐effects models. The summary odds ratios (ORs) for pRB inactive were 0.64 (95% confidence interval [CI]:0.45–0.91, P = 0.01) for T1/T2 versus T3/T4 tumors; summary OR = 0.69 (95% CI:0.51–0.94, P = 0.02) for N0 versus N1 tumors. The association between pRB loss and prognosis was examined in nine studies, and the summary hazard ratio was 1.39 (95% CI:1.11–1.74, P = 0.004). pRB inactive was significant associated with T3/T4 tumors and N1 stage as well as adverse prognosis for ESCCs. It appears warranted to prospectively validate that pRB loss may be used for subdividing the T,N stage evaluation of patients with ESCCs, and these patients may be the preponderant people for individualized treatment or target therapy.     

Factors associated with the presence of multiple Lugol‐voiding lesions in patients with esophageal squamous‐cell carcinoma

Multicentric squamous dysplasia of the esophagus is characterized by multiple Lugol‐voiding lesions (LVLs) on Lugol chromoendoscopy. Multiple LVLs are associated with a very high risk of multiple cancers arising in the esophagus as well as the head and neck. To gain insight into the pathogenesis of multiple LVLs of the esophageal mucosa, we studied risk factors for the development of such lesions in 76 patients who had a current or previous diagnosis of esophageal squamous cell carcinoma. All patients underwent Lugol chromoendoscopy of the esophageal mucosa. The history of tobacco and alcohol use was documented. Polymorphisms of the aldehyde dehydrogenase type 2 (ALDH2) gene were identified by polymerase chain reaction using sequence‐specific primers. Clinical factors related to multiple LVLs were analyzed. All patients with multiple LVLs were drinkers. On univariate analysis, male sex (odds ratio [OR] 15, 95% confidence interval [CI] 1.84–122.45: P = 0.011), presence of the ALDH2‐2 allele (OR 4.5, 95% CI 1.55–13.24: P = 0.006), and smoking index ≥1000 (OR 2.6, 95% CI 1.02–6.6: P = 0.045) were associated with multiple LVLs. On multivariate analysis, male sex (OR 10.02, 95% CI 1.13–88.44: P = 0.038) and presence of the ALDH2‐2 allele (OR 4.56, 95% CI 1.4–14.82: P = 0.012) were associated with multiple LVLs. Among drinkers, a daily alcohol intake of ≥100 g pure ethanol with the ALDH2‐2 allele (OR 17.5, 95% CI 1.97–155.59: P = 0.01) and a daily alcohol intake of <100 g pure ethanol with the ALDH2‐2 allele (OR 8.85, 95% CI 1.68–46.69: P = 0.01) more strongly correlated with multiple LVLs than did a daily alcohol intake of <100 g pure ethanol without the ALDH2‐2 allele, whereas a daily alcohol intake of ≥100 g pure ethanol without the ALDH2‐2 allele (OR 4.0, 95% CI 0.54–29.81: P = 0.18) did not. In conclusion, male sex and the ALDH2‐2 allele are associated with an increased risk for multiple LVLs of the esophageal mucosa in patients with esophageal squamous cell carcinoma. Among drinkers with the ALDH2‐2 allele, the risk of multiple LVLs increased in parallel to the daily alcohol intake.     

Clinical effect of E‐series of prostaglandin receptor 2 and epidermal growth factor receptor signal pathways in the development of esophageal squamous cell carcinoma

Signal pathways mediated by epidermal growth factor receptor (EGFR) and E‐series of prostaglandin receptors (EPs) are closely correlated to the pathogenesis of tumor. This experiment was designed to investigate the expression and clinical significance of EP2 and EGFR in esophageal squamous cell carcinoma (ESCC). Tissue samples were collected reterospectively from 87 patients with ESCC (first diagnosed). The patients were followed up for 5 years after radical surgery. The expression of EP‐2 and EGFR were examined by tissue chip technology and immunohistochemistry methods. Clinicopathological and prognostic impact were evaluated. Overexpression of EGFR and EP‐2 was more observed in ESCC than the control group (58.6% vs. 13.9%; 52.9% vs. 4.88%, P < 0.001, respectively); which correlated with tumor infiltration depth, lymph node metastasis, and tumor‐lymph node‐metastasis staging. Both the EP‐2 and EGFR overexpression were detected in 39 specimens and exhibited the positive correlation (P < 0.001, r = 0.404). Overexpression of EP2 and EGFR exhibited significant correlation with worse 5‐year overall survival than those with negative result (17.6% vs. 27.8%, P = 0.011; 10.9% vs. 34.1%, P < 0.001, respectively). Cox proportional hazard model showed that the T‐staging, lymph node metastasis, and EGFR overexpression were the independent risk factors of the prognosis. The present study exhibited that the overexpression of EP2 and EGFR in ESCC tissues might play an important role in carcinogenesis and the progression of ESCC.     

Original article: Upregulation of caspase‐3 expression in esophageal cancer correlates with favorable prognosis: an immunohistochemical study from a high incidence area in northern China

Caspase‐3 plays an important role as the key effector during apoptosis, but there are very few studies of caspase‐3 in esophageal squamous cell carcinoma (ESCC). The purpose of this study was to investigate the expression and prognostic significance of caspase‐3 in ESCC from Linzhou City, a high incidence area in northern China. All 64 patients underwent esophagectomy for ESCC between January 2002 and December were enrolled in this study. Caspase‐3 expression was assessed by immunohistochemistry (IHC) in primary ESCC and paired normal esophageal epithelium. The positive rate of caspase‐3 expression was higher in ESCC than in normal esophageal epithelium (79.7% vs. 50.0%, Chi‐square = 12.372, P= 0.001). Caspase‐3 expression was correlated with tumor cell differentiation (Phi = 0.717, P < 0.001), tumor infiltration depth (Phi =?0.334, P= 0.008), and pathologic TNM (pTNM) staging (rs =?0.268, P= 0.032). Patients in caspase‐3 positive group had a significantly better 5‐year overall survival than those in the negative group (77.4% vs. 35.9%, χ²= 7.344, P= 0.007). Our results showed that caspase‐3 expression was upregulated in ESCC compared with normal esophageal epithelium in population of Chinese high incidence area, and patients with caspase‐3 positive expression had better prognosis. Therefore, caspase‐3 immunostaining could be a simple and useful tool for predicting survival in ESCC patients.     

Cytotoxic T-lymphocyte antigen 4 gene +49A/G polymorphism significantly associated with susceptibility to primary biliary cirrhosis: a meta-analysis

OBJECTIVE: To evaluate comprehensively the association of cytotoxic T‐lymphocyte antigen 4 (CTLA‐4) +49A/G polymorphism with susceptibility to primary biliary cirrhosis (PBC). METHODS: PubMed was used to search for the relevant published articles. The risk of PBC association with the CTLA‐4+49A/G polymorphism was estimated for each study in a random‐effects model. Odds ratio (OR) and 95% confidence interval (CI) were estimated for each study. Risks to PBC were estimated by stratified analysis in patients with different ethnicity and antimitochondrial antibody (AMA) status, as well as histological stages. RESULTS: A total of 12 articles were included in the study. An association between PBC and CTLA‐4 G allele was found, overall OR = 1.20, 95% CI 1.03–1.41 (P = 0.02). However, stratification by ethnicity indicated a significant association between the G allele and PBC in Asians (OR = 1.36, 95% CI 1.12–1.65, P = 0.002), but not in Caucasians (OR = 1.15, 95% CI 0.95–1.39, P = 0.15). Moreover, AMA positive patients carrying G allele were more susceptible to PBC compared with AMA negative patients (OR = 1.23, 95% CI 1.06–1.43, P = 0.007; OR = 0.98, 95% CI 0.71–1.34, P = 0.88, respectively). CONCLUSIONS: Polymorphism in exon 1 of CTLA‐4 gene at position 49 may act as a candidate of susceptibility locus to PBC. However, larger studies with participants of varying ethnicity and stratified by clinical and laboratory characteristics are needed to validate our findings.     

Interleukin‐1β and ‐10 polymorphisms influence erosive reflux esophagitis and gastritis in Taiwanese patients

Background and Aims: Helicobacter pylori (H. pylori) infection induces cytokine production and is associated with gastrointestinal diseases. This study examined the relationship of gene polymorphisms, including interleukin (IL)‐1β, ‐10, ‐8, and tumor necrosis factor‐α (TNF‐α), H. pylori infection, and susceptibility to gastrointestinal disorders in Taiwanese patients. Methods: IL‐1β?511/?31/+3953, ‐10?1082/?819/?592, ‐8?251, and TNF‐α?308 polymorphisms were assessed in 628 gastrointestinal disease patients, and 176 healthy controls were analyzed using the polymerase chain reaction?restriction fragment length polymorphism method. Results: IL‐1β?511 T/T and ?31 C/C genotypes, and IL‐1β?511 T and ?31 C alleles were associated with an increased risk of reflux esophagitis (P = 0.034, odds ratio [OR] = 1.384, 95% confidence interval [CI]: 1.023–1.871; P = 0.031, OR = 1.388, 95% CI: 1.028–1.873; P = 0.044, OR = 1.342, 95% CI: 1.008–1.786; and P = 0.040, OR = 1.349, 95% CI: 1.014–1.796, respectively). No relationship was found between H. pylori infection and the risk of reflux esophagitis. IL‐10?819 C/T and ‐10?592 A/C genotypes and IL‐10?1082/?819/?592 ATA/ACC and ATA/GCC haplotypes were associated with an increased risk of gastritis (P = 0.021, OR = 1.721, 95% CI: 1.084–2.733; P = 0.016, OR = 1.766, 95% CI: 1.112–2.805; P = 0.039, OR = 1.662, 95% CI: 1.024–2.697; and P = 0.035, OR = 1.600, 95% CI: 1.024–2.499, respectively). Conclusion: Among Taiwanese patients, IL‐1β and ‐10 polymorphisms were associated with an increased risk of erosive reflux esophagitis and gastritis, respectively.     

Risk factors for lymph node metastasis in T1 esophageal squamous cell carcinoma: A systematic review and meta-analysis

BACKGROUND Lymph node metastasis(LNM)affects the application and outcomes of endoscopic resection in T1 esophageal squamous cell carcinoma(ESCC).However,reports of the risk factors for LNM have been controversial.AIM To evaluate risk factors for LNM in T1 ESCC.METHODS We searched Embase,PubMed and Cochrane Library to select studies related to LNM in patients with T1 ESCC.Included studies were divided into LNM and non-LNM groups.We performed a meta-analysis to examine the relationship between LNM and clinicopathologic features.Odds ratio(OR),mean differences and 95%confidence interval(CI)were assessed using a fixed-effects or randomeffects model.RESULTS Seventeen studies involving a total of 3775 patients with T1 ESCC met the inclusion criteria.After excluding studies with heterogeneity based on influence analysis,tumor size(OR=1.93,95%CI=1.49-2.50,P<0.001),tumor location(OR=1.46,95%CI=1.17-1.82,P<0.001),macroscopic type(OR=3.17,95%CI=2.33-4.31,P<0.001),T1 substage(OR=6.28,95%CI=4.93-8.00,P<0.001),differentiation(OR=2.11,95%CI=1.64-2.72,P<0.001)and lymphovascular invasion(OR=5.86,95%CI=4.60-7.48,P<0.001)were found to be significantly associated with LNM.Conversely,sex,age and infiltrative growth pattern were not identified as risk factors for LNM.CONCLUSION A tumor size>2 cm,lower location,nonflat macroscopic type,T1b stage,poor differentiation and lymphovascular invasion were associated with LNM in patients with T1 ESCC.     

Association of Vitamin D Receptor Gene Polymorphism With the Risk of Nephrolithiasis

This study aimed to explore the relationship between vitamin D receptor (VDR) gene polymorphisms and the risk of nephrolithiasis. All relevant trials were searched from multiple databases according to predefined criteria, the pooled OR and corresponding 95% CI were analyzed using Stata software. Seventeen studies involving 2441 cases and 2296 controls were included. The pooled analysis showed that VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with nephrolithiasis susceptibility either in Asian and in Caucasians populations. VDR TaqI gene polymorphism was associated with nephrolithiasis in the overall populations (T vs. t: OR = 0.84, 95% CI: 0.73–0.95, P = 0.006; TT vs. Tt + tt: OR = 0.79, 95% CI: 0.66–0.95, P = 0.010). In Asian population, VDR TaqI gene polymorphism also was associated with nephrolithiasis susceptibility (TT vs. Tt + tt: OR = 0.72, 95% CI: 0.55–0.93, P = 0.012; Tt vs. TT + tt: OR = 1.43, 95% CI: 1.00–2.05, P = 0.048). But TaqI gene polymorphism was not associated with nephrolithiasis risk in Caucasian populations (T vs. t: OR = 0.85, 95% CI: 0.72–1.00, P = 0.051; TT vs. Tt + tt: OR = 0.87, 95% CI: 0.68–1.10, P = 0.245; tt vs. Tt + TT: OR = 1.32, 95% CI: 0.86–2.01, P = 0.206; Tt vs. TT+ tt: OR = 0.98, 95% CI: 0.70–1.38, P = 0.931). VDR BsmI, FokI, and ApaI gene polymorphisms were not associated with the risk of nephrolithiasis either in Asian and Caucasians populations, but VDR TaqI gene polymorphism was associated with nephrolithiasis in the Asian subjects.     

Hormonal and reproductive factors and risk of esophageal cancer in women: a meta‐analysis

Currently published studies on the relationship between hormonal and reproductive factors and esophageal cancer (EC) risk in women have yielded contradictory findings. For a better understanding of this relationship, we first performed this meta‐analysis by pooling all available publications. Sixteen independent studies were retrieved after a comprehensive search in PubMed and Embase databases. The pooled relative risks (RRs) with 95% confidence intervals (95% CIs) were calculated. The pooled RRs implicated that hormone replacement therapy was negatively associated with the risk of EC (RR = 0.72, 95% CI 0.60–0.86, P < 0.001) and esophageal squamous cell carcinoma (RR = 0.68, 95% CI 0.48–0.97, P = 0.031). Menopausal women were at an increased risk of EC (RR = 1.47, 95% CI 1.07–2.03, P = 0.018), particularly esophageal squamous cell carcinoma (RR = 1.66, 95% CI 1.12–2.48, P = 0.012). Additionally, decreased risk of EC (RR = 0.79, 95% CI 0.68–0.92, P = 0.003) and esophageal adenocarcinoma (RR = 0.66, 95% CI 0.53–0.82, P < 0.001) was demonstrated among women with breast‐feeding history. Moreover, such associations were more significant among Caucasians, but not Asians. Our study suggests that menopause is an independent risk factor for EC, while hormone replacement therapy and breast‐feeding history play a protective role against EC, particularly among Caucasians. All results are consistent with the hypothesis that effects of estrogen may lower the risk of EC in women.     

Association of genetic polymorphisms in PTEN and additional gene–gene interaction with risk of esophageal squamous cell carcinoma in Chinese Han population

This study aims to investigate the association of five single nucleotide polymorphisms (SNPs) in the phosphatase and tensin homologue (PTEN) gene and additional role of gene–gene interaction with esophageal squamous cell carcinoma (ESCC), based on a Chinese case–control study. A total of 871 subjects (420 males and 451 females) were selected, including 425 ESCC cases and 446 controls. Five SNPs were selected for genotyping in the case–control study: rs2735343, rs555895, rs2299939, rs17431184 and rs701848. Logistic regression model was used to examine the association between five SNP and ESCC, and additional interaction among five SNP, odds ratio (OR) and 95% confident interval (95%CI) were calculated. All genotypes were distributed according to Hardy–Weinberg equilibrium in controls. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk than those with wild‐type homozygotes, and OR (95%CI) were 1.27 (1.09–2.08) and 1.45 (1.17–1.98), respectively. We also found a potential gene–gene interaction between rs2735343 and rs701848 (P = 0.0010), and a potential gene–gene interaction among all five SNP (P = 0.0107) after covariates adjustment. Subjects with TC or CC of rs2735343 and TC or CC of rs701848 genotype have highest ESCC risk, compared to subjects with TT of rs2735343 and TT of rs701848 genotype, OR (95% CI) was 2.76 (1.37–3.45) after covariates adjustment. The carriers of homozygous mutant of rs2735343 and rs701848 polymorphism revealed increased ESCC risk. We also found a potential gene–gene interaction between rs2735343 and rs701848 and a potential gene–gene interaction among all five SNPs.     

Original article: The expression of CFL1 and N‐WASP in esophageal squamous cell carcinoma and its correlation with clinicopathological features

Cofilin1 (CFL1) is an actin‐modulating protein, which belongs to the ADF/Cofilin family. Neural Wiskott–Aldrich syndrome protein (N‐WASP) is the key regulator of the actin cytoskeleton, a member of Wiskott‐Aldrich syndrome protein family. They have been suggested to be involved in cancer cell invasion and metastasis. In this study, the expression patterns of CFL1 and N‐WASP in normal esophageal mucosa and esophageal squamous cell carcinoma (ESCC) and their correlation with clinical characteristics were investigated. Immunohistochemical staining showed that CFL1 was expressed in nuclear and cytoplasm of cancer cells. However, N‐WASP was mainly found in the cytoplasm of the cancer cells. There were significant evidences that proved that CFL1 is correlated with clinicopathological factors in ESCC, such as infiltration depth, lymph node metastasis and pathological staging (P < 0.05). It is also proved that N‐WASP is related to lymph node metastasis and pathological staging in ESCC (P < 0.05). Kaplan–Meier analysis showed that there was no correlation between CFL1 and N‐WASP protein expression and survival (P > 0.05). Moreover, the mRNA expression of CFL1 and N‐WASP was detected by quantitative real time PCR in 70 tissue specimens. The results showed that CFL1 mRNA level was over‐expressed in ESCC tissue (P < 0.05), while N‐WASP mRNA expression level was not different between cancerous tissues and adjacent normal esophageal mucosa (P > 0.05). Also, CFL1 mRNA expression was significantly associated with regional lymph node metastasis and pathological staging (P < 0.05). Kaplan–Meier analysis showed that there was no correlation between CFL1 and N‐WASP mRNA expression and survival (P > 0.05). Our findings suggested that CFL1 and N‐WASP may play an important role in the tumorigenesis of ESCC, and to be the candidate novel biomarkers for the diagnosis and prognosis of ESCC. These findings may have implications for targeted therapies in patients with ESCC.     

Preterm birth and risk of type 1 and type 2 diabetes: systematic review and meta‐analysis

Preterm birth is suggested to play an important role in the development of diabetes. However, results have been inconsistent. We conducted a systematic review and meta‐analysis to clarify the relationship between preterm birth and type 1 and type 2 diabetes. PubMed, Embase and ISI Web of Science were searched. A total of 18 studies (including 2,176,480 participants and 22,073 cases) for type 1 diabetes and five studies (including 31,478 participants and 1,898 cases) for type 2 diabetes were included in the current meta‐analyses. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) using fixed‐effects model to evaluate the relations between preterm birth and type 1 and type 2 diabetes. The results suggested that preterm birth was significantly associated with increased risk of type 1 diabetes (OR = 1.18, 95% CI = 1.11–1.25), with no evidence of between‐study heterogeneity (I² = 13.2%, P = 0.296). Preterm birth was also significantly associated with increased risk of type 2 diabetes (OR = 1.51, 95% CI = 1.32–1.72), with no evidence of (I² = 0.0%, P = 0.557). Subgroup analyses suggested that there was significant association in both case‐control studies (OR = 1.16, 95% CI = 1.06–1.26) and cohort studies (relative risk = 1.20, 95% CI = 1.11–1.29) for type 1 diabetes, and similar results were found for type 2 diabetes. The results suggested that preterm birth was a significant and independent risk factor for both type 1 and type 2 diabetes.     

Association and Interaction of −58C>T and ±9 bp Polymorphisms of BDKRB2 Gene Causing Susceptibility to Essential Hypertension

Introduction. Bradykinin, a vasodilator by nature has been documented to have a protective role against hypertension and cardiovascular complications. Polymorphisms of bradykinin B2 receptor (BDKRB2) gene are reported to be predisposing factors for hypertension. Evaluation of the association between ?58C>T and ±9 bp polymorphisms of BDKRB2 with essential hypertension (EHT) was attempted. Methods. Two hundred and fourteen primary hypertensives and 249 controls were genotyped for the selected markers by polymerase chain reaction, gel electrophoresis (±9 bp), and SSCP (?58C>T). Results. While ?58C>T polymorphism did not reveal any association with EHT, ±9 bp polymorphism showed a significant association with high risk for heterozygotes (+9/?9) when tested against the pooled frequencies of homozygotes (OR [odds ratio] = 1.63, 95% confidence interval [CI] = 1.12–2.38, P = .02), and this risk was 1.7 folds high in males (OR = 1.74, 95% CI = 1.05–2.86, P = .06) and 1.9 folds high in familial cases (OR = 1.96, 95% CI = 1.09–3.53, P = .04). In contrast, significant protective effect was observed for ?9/–9 genotype against EHT when tested under dominant model in general (OR = 0.59, 95% CI = 0.41–0.86, P = .01), in males (OR = 0.49, 95% CI = 0.30–0.82, P = .01), and in familial cases (OR = 0.50, 95% CI = 0.28–0.89, P = .04). Significant risk for +9 bp allele was observed in general (OR = 1.39, 95% CI = 1.05–1.86, P = .04) and in males (OR = 1.65, 95% CI = 1.13–2.41, P = .02). The interaction information analysis revealed a synergistic effect between the two polymorphisms contributing to EHT. +9/+9 genotype of ±9 bp polymorphism when present in combination with CC genotype of ?58C>T polymorphism showed 2.2-fold higher risk for developing EHT. Conclusions. The results suggest that allele +9 bp might be a risk factor for EHT in general and specially in males. Markers ?58C>T and ±9 bp may act synergistically causing susceptibility to EHT.