Caveolin-1 promotes an invasive phenotype and predicts poor prognosis in large cell lung carcinoma

Purpose

This study investigated the relationships of caveolin-1 expression with clinical pathologic parameters and the prognosis of patients with large cell lung carcinoma. This study also explored the roles of caveolin-1 in cell invasiveness, matrix metalloproteinase (MMP) expression, and non-small cell lung carcinoma activity in vitro.

Methods

A total of 120 tissue samples were immunohistochemically analyzed for caveolin-1 expression. Cell invasion ability was measured by a Transwell invasion assay. Protein expression was assessed by Western blotting. MMP activity was detected by gelatin zymography.

Results

Caveolin-1 was expressed in 54 of 120 (45.0%) cases of large cell lung carcinoma. Caveolin-1 expression was significantly correlated with node status (N0 vs. N1, N2, and N3; P = 0.005) and advanced pTNM stage (Stages I and II vs. Stage III, P < 0.001). Patients with caveolin-1-positive expression had a poorer prognosis than did those with caveolin-1-negative expression (P < 0.001). The knockdown of caveolin-1 in H460 and 95D cells reduced the invasive ability of the cells and the expression of phosphorylated epidermal growth factor receptor (EGFR), phospho-extracellular signal-regulated kinases 1 and 2, MMP2, and MMP9; the protein level and activity of MMP2 and MMP9 were also decreased by the inhibition of EGFR activity in H460 and 95D cells.

Conclusions

The expression of caveolin-1 was positively correlated with an advanced pathologic stage. Thus, caveolin-1 could act as a predictor of a poor prognosis in patients with large cell lung carcinoma. In addition, the downregulation of caveolin-1 reduced both the invasive ability of tumor cells and the protein and activity levels of MMP2 and MMP9 in vitro, suggesting the involvement of EGFR/MMP signaling in this process.     

MiR-196a2 rs11614913 T > C polymorphism and risk of esophageal cancer in a Chinese population

Background

Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. Methods: We conducted a hospital based case–control study to evaluate the genetic susceptibility of functional single nucleotide polymorphisms (SNPs) in the microRNAs on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The miR-196a2 rs11614913 T > C, miR-146a rs2910164 C > G, miR-499 rs3746444 T > C, miR-26a-1 rs7372209 C > T and miR-27a rs895819 T > C genotypes were determined using a custom-by-design 48-Plex SNPscan™ Kit and matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS).

Results

MiR-196a2 rs11614913 T > C polymorphism was associated with borderline statistically decreased risk of ESCC. In the recessive model, when the miR-196a2 rs11614913 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a borderline statistically decreased risk for ESCC (adjusted OR 0.72, 95% CI 0.50–1.03, p = 0.070). In stratification analyses, a significantly decreased risk of ESCC associated with the miR-196a2 rs11614913 T > C polymorphism was evident among women patients and patients who never smoking or drinking.

Conclusions

These findings indicated that functional polymorphism miR-196a2 rs11614913 T > C might contribute to decreased ESCC risk among women patients and patients who never smoking or drinking. However, our results were obtained with a limited sample size. Future larger studies with other ethnic populations and tissue-specific biological characterization are required to confirm current findings.     

High ERCC1 expression predicts cisplatin-based chemotherapy resistance and poor outcome in unresectable squamous cell carcinoma of head and neck in a betel-chewing area

Background  

This study was to evaluate the effect of excision repair cross-complementation group 1(ERCC1) expression on response to cisplatin-based induction chemotherapy (IC) followed by concurrent chemoradiation (CCRT) in locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) patients.     

Relative lymphocyte count is a prognostic parameter in cancer patients with catumaxomab immunotherapy

Background

Catumaxomab (anti-EpCAM × anti-CD3) treatment in peritoneal carcinomatosis (PC) of EpCAM-positive cancers was effective in phase I and II studies. Recently, it was approved in the EU for treatment of peritoneal carcinomatosis and malignant ascites. Aim of this hypothesis-generating study was to identify predictive or prognostic biomarkers with relevance for overall survival.

Methods

34 patients with PC in phase I/II studies with catumaxomab treatment were assessed for age, Karnofsky Index (KI), relative (RLC) and absolute lymphocyte count, relative and absolute granulocyte count, T-cell subsets, NK cells, and monocytes before catumaxomab therapy. Disease control (responder) was defined by stable disease, partial response or complete response (RECIST v1.0) >3 months or survival >6 months. Correlation analysis, Kaplan–Meier curves, ROC calculation, and multivariate regression were used for statistical analysis.

Results

Mean RC values significantly differed between the non-responder (14.0%) and the responder group (23.9%; p = 0.001). RLC was correlated with overall survival (p = 0.03). RLC of >12% defined by ROC calculation was associated with prolonged survival (p = 0.035; hazard ratio of 2.775 for patients with RLC <12%). Patients with RLC >12% showed a mean survival of 15.6 versus 5.6 months in patients with RLC ?12% (p = 0.001). Multivariate analysis found the individual RLC before therapy (p = 0.039) and the KI performance status (p = 0.002) to be independent prognostic parameters. Increasing KI by 1% resulted in a risk decrease of 10.1%. Increasing RLC by 1% resulted in a risk decrease of 4.6%. Age and the extent of PC did not significantly influence survival.

Conclusions

RLC and KI were identified as potential prognostic parameters for superior disease control and overall survival after catumaxomab treatment. RLC may be used as a biomarker to indicate a suitable immune status for catumaxomab therapy. The predictive impact has to be confirmed in further studies.     

Efficacy and safety of Huachansu combined with chemotherapy in advanced gastric cancer: A meta-analysis

Background

Huachansu, a Chinese medicine that comes from dried toad venom from the skin glands of Bufo bufo gargarizans Cantor or Bufo melanostictus Schneider, has been used in treatment of cancers. We conducted a meta-analysis to evaluate the efficacy and safety of Huachansu combined with chemotherapy for advanced gastric cancer.

Methods

The main efficacy measures were total response rates, quality of life and one-year survival rate. We also assessed the safety of treatments by evaluating the rate of occurrence of gastrointestinal side effects, leucocytopenia and neurotoxicity. The pooled relative ratio (RR) with 95% confidence interval (95% CI) was calculated to estimate the efficacy and safety of Huachansu combined with chemotherapy.

Results

Fifteen randomized controlled trails were eligible. The result showed that Huachansu combined with chemotherapy was superior to simple chemotherapy treatment in increasing of total response rate [RR = 1.28; 95% CI: (1.11, 1.18)] and Karnofsky score [RR = 1.31; 95% CI: (1.18, 1.45)], and reducing gastrointestinal side effects [RR = 0.71; 95% CI: (0.61, 0.82)], and leucocytopenia [RR = 0.75; 95% CI: (0.64, 0.87)]; there was no significant difference on one-year survival rate (RR = 1.25; 95% CI: 0.73, 2.14) between combination group and simple chemotherapy group.

Conclusion

Compared with chemotherapy control group, Huchansu combined with chemotherapy provide benefits for advanced gastric cancer on improving the response rate, increasing Karnofsky score, reducing leucocytopenia and major side effects such as gastrointestinal side effects caused by chemotherapy.     

The relationship between tumor size and stage in early versus advanced ovarian cancer

Background

Ovarian cancer has a different prognosis between early (I and II) and advanced stage (III and IV). The mechanism of disease progression is unknown, but patients with advanced disease may have a higher propensity for seeding of the abdominal cavity early in the disease process than those with early stage. Theoretically if this is so, then patients with advanced stage should have smaller sized tumors than patients with early stage.

Methods

This was a retrospective chart review of patients in the tumor registry in 2003–2006. Patients had epithelial ovarian cancer, other cell types were excluded. Only cases with documentation of surgical and pathologic staging and measured dimensions on pathologic specimen were included. Patient stage and all available dimensions measured on diseased ovaries were recorded. The dimensions for each patient were averaged into a single dimension for that patient, and then these measurements were totaled and averaged.

Results

There were 110 patients analyzed: 85 with advanced disease, 25 with early stage. The average measurement was 4.8 cm in advanced disease, and was 10.7 cm in early stage disease. This difference was statistically significant (p < 0.001).

Conclusions

Overall, patients with early stage ovarian cancer have diseased ovaries that are more than twice as large as those found in advanced disease. This finding supports the fact that early versus advanced ovarian cancer are 2 separate disease processes. Early stage grows locally and does not disseminate, and advanced stage disseminates while the tumor is still relatively small. Theoretically there may be a factor that separates these 2 into different diseases, where advanced disease patients have a substance produced by their tumor that allows for early dissemination, and early stage lacks this substance and only grows locally. Basic science research comparing the tissue microarrays of early versus advanced stage disease may be able to identify this difference. If the difference is found, perhaps therapy can be targeted against this difference, and screening tests for advanced ovarian cancer can be improved.     

The influence of limited English proficiency on outcome in patients treated with radiotherapy for head and neck cancer

Objective

To evaluate how limited English proficiency affects treatment outcome in head and neck cancer (HNC) patients treated with curative intent radiation therapy (RT).

Methods

From 2004 to 2010, 131 patients with HNC underwent RT. Patient's self-reported primary language and race/ethnicity were obtained at hospital registration. English proficiency was categorized as being English proficient (EP) or limited English proficient (LEP). Race/ethnicity was categorized as white, black and other (Hispanics and Asians). Patients were evaluated for locoregional (LRC), distant control (DC), overall (OS) and disease-free (DFS) survival.

Results

Fewer LEP patients (60.0%) underwent chemoradiation compared to EP (83.8%), P = 0.028. The three-year actuarial LRC for EP and LEP patients was 82.2% and 58.3%, respectively, P = 0.038. LEP patients had an increased risk of locoregional failure on univariate Cox regression analysis (hazard ratio, HR 2.4, 95% CI, 1.0–5.8). No differences by English proficiency were seen for DC, OS and DFS. Race/ethnicity was not associated LRC, DC, OS and DFS.

Conclusion

Inferior locoregional control was observed in LEP patients receiving RT for HNC. Potential health disparities as a result of limited English proficiency require further investigation.

Practice implications

Patient education, use of culturally sensitive interpreter and patient navigation services, and improved patient compliance should be considered in head and neck cancer patients receiving complex multidisciplinary care.     

Evaluation of a treatment and teaching refresher programme for the optimization of intensified insulin therapy in type 1 diabetes

Objective

Evaluation of an ambulatory diabetes teaching and treatment refresher programme (DTTP) for the optimization of intensified insulin therapy in patients with type 1 diabetes (refresher course).

Methods

85 outpatients took part in this prospective multicentre trial. Metabolic and psychosocial data were analyzed at baseline (V1), 6 weeks (V2) and 12 months after DTTP (V3).

Results

In patients with baseline HbA1c > 7% (88%), HbA1c decreased by 0.36% (p = 0.004). The percentage of patients with HbA1c ≤ 7% increased from 21.3 to 34.9% and with HbA1c above 10% decreased from 6.6 to 1.6% at V3. The incidence of hypoglycaemia decreased significantly: non severe hypoglycaemia from 3.31 to 1.39 episodes/pat/week (p = 0.001) and severe hypoglycaemia from 0.16 to 0.03 episodes/pat/year (p = 0.02). The treatment satisfaction increased by +10 of maximal ±18 points. The negative influence of diabetes on quality of life decreased from −1.93 to −1.69 points (p = 0.031).

Conclusion

In a group of patients with moderately controlled diabetes type 1 who were already treated with intensified insulin therapy, metabolic control, treatment satisfaction and quality of life were improved after participation in an ambulatory DTTP without increasing insulin dosage, number of injections or insulin species.

Practice implications

This DTTP is effective for the optimization of intensified insulin therapy.     

SNPs in the exons of Toll-like receptors are associated with susceptibility to type 1 diabetes in Chinese population

Objective

Toll-like receptors (TLRs) recognize a wide range of pathogen-associated molecular patterns (PAMP) and mount the initiation of immune response. Single nucleotide polymorphisms (SNPs) in exons of genes encoding TLRs might be responsible for the generation of an abnormal immune response which could lead to autoimmune diseases. In this study, we investigated the SNPs in TLRs in a Chinese population, and we hypothesized that SNPs in TLRs are associated with type 1 diabetes (T1D), an autoimmune disease caused by destruction of insulin producing pancreatic β-cells, in the studied population.

Research design and methods

We selected 28 SNPs in exons of TLRs with an aim to identify those that might have a direct correlation with T1D etiology and many have not been included in previous GWAS studies. Genotyping of those SNPs in TLRs was performed in 429 T1D patients and 300 age and gender-matched healthy controls in Chinese Han population which was not included in the earlier GWAS studies.

Results

Among the SNPs genotyped, the T allele of TLR1–626 was positively associated with T1D (OR = 1.98, Pc = 0.01). We identified another T1D association locus in TLR6: the homozygous AA genotype of TLR6-1329 was negatively and heterozygous GA was positively associated with T1D (OR = 0.54, Pc = 0.02 and OR = 1.70, Pc = 0.03, respectively). We also identified the haplotype T-G-A in TLR1 gene to be positively associated with T1D (OR = 2.22, Pc = 0.03). Additional haplotypes in TLR-6 also showed significant positive and negative association. In addition, our haplotype analysis and conditional analysis showed that these two SNPs are the primary T1D associated loci among the SNPs tested in our cohort in each TLR gene.

Conclusion

SNPs and haplotypes in TLR1 and TLR6 gene were associated with T1D in Chinese Han population. Our study, for the first time, indicates that TLR1 and TLR6 gene might play important roles in the etiology of T1D.     

Correlation of microRNA-375 downregulation with unfavorable clinical outcome of patients with glioma

Background and aim

MicroRNA-375 (miR-375) is frequently demonstrated to be frequently dysregulated and functions as a tumor suppressor or an oncogene in different cancer types. However, its roles in human gliomas have not been reported. The aim of this study was to investigate the expression pattern and clinical significance of miR-375 in patients with gliomas.

Methods

Real-time quantitative RT-PCR assay was performed to detect miR-375 expression in human gliomas and non-neoplastic brain tissues. Then, the association of miR-375 expression with clinicopathological factors and prognosis of glioma patients was also statistically analyzed.

Results

miR-375 expression was significantly decreased on average in glioma tissues relative to non-neoplastic brain tissues (P < 0.0001) with ascending pathological grade. Then, the low miR-375 expression in glioma tissues was significantly associated with advanced pathological grade (P = 0.003) and low Karnofsky performance score (KPS, P = 0.01). Moreover, both univariate and multivariate Cox regression analyses determined that loss of miR-375 expression effectively predicted the decreased overall survival in patients with gliomas.

Conclusions

These findings offer the first convinced evidence that the downregulation of miR-375 expression in human gliomas may play an inhibitory role during the tumor development. This miRNA might function as a candidate unfavorable prognostic marker for human gliomas.     

Characteristics associated with empathic behavior in Japanese oncologists

Objective

Oncologists must have empathy when breaking bad news to patients who have incurable advanced cancer, and the level of empathy often depends on various individual characteristics. This study aimed to clarify the relationship between these characteristics and empathic behavior in Japanese oncologists.

Methods

We videotaped consultations in which oncologists conveyed news of incurable advanced cancer to simulated patients. Oncologists’ empathetic behaviors were coded, and regression analysis was performed to determine the existence of any relationships with factors such as age, sex, and specialism.

Results

Sixty oncologists participated. In a multivariate model, only age was related to the empathy score (r = 0.406, p = 0.033); younger oncologists scored higher than did older oncologists.

Conclusions

We found that empathic behaviors were more frequent in younger oncologists.

Practice implications

This information could be useful in determining the best approach for implementing future empathy and communication training programs for experienced oncologists in Japanese medical institutions.     

A text messaging intervention to promote medication adherence for patients with coronary heart disease: A randomized controlled trial

Objective

Pharmacologic treatment for secondary prevention of coronary heart disease (CHD) is critical to prevent adverse clinical outcomes. In a randomized controlled trial, we compared antiplatelet and statin adherence among patients with CHD who received: (1) text messages (TM) for medication reminders and education, (2) educational TM only, or (3) No TM.

Methods

A mobile health intervention delivered customized TM for 30 days. We assessed and analyzed medication adherence with electronic monitoring devices [Medication Event Monitoring System (MEMS)] by one-way ANOVA and Welch tests, two-way TM response rates by t-tests, and self-reported adherence (Morisky Medication Adherence Scale) by Repeated Measures ANOVA.

Results

Among 90 patients (76% male, mean age 59.2 years), MEMS revealed patients who received TM for antiplatelets had a higher percentage of correct doses taken (p = 0.02), percentage number of doses taken (p = 0.01), and percentage of prescribed doses taken on schedule (p = 0.01). TM response rates were higher for antiplatelets than statins (p = 0.005). Self-reported adherence revealed no significant differences among groups.

Conclusion

TM increased adherence to antiplatelet therapy demonstrated by MEMS and TM responses.

Practice implications

Feasibility and high satisfaction were established. Mobile health interventions show promise in promoting medication adherence.     

Glycemic control in young children with diabetes: The role of parental health literacy

Objective

This cross sectional study examined the relationship between parental health literacy (HL), diabetes related numeracy, and parental perceived diabetes self-efficacy on glycemic control in a sample of young children with Type 1 DM.

Methods

Seventy primary caregivers of children (age 3–9 years) with Type 1 DM were recruited and surveyed at diabetes outpatient clinic visits. Patients’ medical histories were obtained by medical chart review.

Results

Parental diabetes related numeracy (r = −.52, p < 01), but not reading skills (r = −.25, p = NS) were inversely correlated with the child's glycemic control (HbA1c). Parental perceived diabetes self-efficacy was also negatively correlated to their child's HbA1c (r = −.47, p < 01). When numeracy and parental perceived diabetes self-efficacy were included as predictors of HbA1c, the model was significant (F = 12.93, p < .01) with both numeracy (β = −.46, p < .01) and parental perceived diabetes self-efficacy (β = −.36, p = .01) as significant predictors of HbA1c.

Conclusions

Data from this study highlight the importance of considering the role of parental numeracy, in health outcomes for children with Type 1 DM.

Practice implications

Practitioners should assess parental health literacy and consider intervention when needed.     

Motivational cues as real-time feedback for changing daily activity behavior of patients with COPD

Objective

To investigate how COPD patients respond to motivational cues that aim to improve activity behavior and how these responses are related to cue- and context characteristics. In addition, to explore whether activity can be increased and better distributed over the day by providing such cues.

Methods

Fifteen COPD patients participated. Patients used an activity sensor with a smartphone for four weeks, at least four days/week. Patients received motivational cues every 2 h with advice on how to improve their activity, on top of real-time visual feedback. The response was calculated by the amount of activity 30 min before and after a cue.

Results

In total, 1488 cues were generated. The amount of activity significantly decreased in the 30 min after a discouraging cue (p < 0.001) and significantly increased (p < 0.05) in the 10 min after an encouraging cue. The activity level increased with 13% in the intervention period compared to corrected baseline (p = 0.008). The activity was not more balanced over the day.

Conclusions

COPD patients significantly change their activity level in response to motivational cues, based on continuous ambulatory assessment of activity levels.

Practice implications

Motivational cues could be a valuable component of telemedicine interventions that aim to improve activity behavior.     

How poorer quality of life in adolescence predicts subsequent type 1 diabetes management and control

Objective

Detriments in quality of life (QOL) may contribute to the common, costly decline in adolescents’ type 1 diabetes management and control, yet we know little about how this might happen.

Methods

Participants were 150 adolescents (age 13–18) with type 1 diabetes and their parents. We constructed a latent QOL variable from a multi-informant, multi-domain assessment when participants entered the study. The QOL variable was examined in relation to prospective assessments of diabetes management (blood glucose monitoring frequency; BGM) and control (hemoglobin A1c). We used an indirect path model to test the links among these variables, using bias-corrected bootstrapping.

Results

Poorer QOL at baseline was indirectly linked with higher A1c at 12 months via less frequent BGM obtained at 6 months (b = −0.01, 95% CI = −0.025, −0.004, p < 0.05). Older age (b = −0.32), longer diabetes duration (b = −0.07), and insulin delivery via injections versus the insulin pump (b = 0.67) were covariates of less frequent BGM, and unmarried caregiver status was associated with higher A1c (b = −0.76), all ps < 0.05.

Conclusions

In this study, poorer QOL acted as a barrier to effective diabetes management, subsequently altering diabetes control.

Practice implications

Efforts to monitor and enhance QOL may hold promise for improving adolescents’ diabetes outcomes in the future.     

Development and validation of the diabetes adolescent problem solving questionnaire

Objective

Problem solving is a critical diabetes self-management skill. Because of a lack of clinically feasible measures, our aim was to develop and validate a self-report self-management problem solving questionnaire for adolescents with type 1 diabetes (T1D).

Methods

A multidisciplinary team of diabetes experts generated questionnaire items that addressed diabetes self-management problem solving. Iterative feedback from parents and adolescents resulted in 27 items. Adolescents from two studies ( N= 156) aged 13–17 were recruited through a pediatric diabetes clinic and completed measures through an online survey. Glycemic control was measured by HbA1c recorded in the medical record.

Results

Empirical elimination of items using principal components analyses resulted in a 13-item unidimensional measure, the diabetes adolescent problem solving questionnaire (DAPSQ) that explained 56% of the variance. The DAPSQ demonstrated internal consistency (Cronbach's alpha = 0.92) and was correlated with diabetes self-management (r = 0.53, p < .001), self-efficacy (r = 0.54, p < .001), and glycemic control (r = −0.24, p < .01).

Conclusion

The DAPSQ is a brief instrument for assessment of diabetes self-management problem solving in youth with T1D and is associated with better self-management behaviors and glycemic control.

Practice implications

The DAPSQ is a clinically feasible self-report measure that can provide valuable information regarding level of self-management problem solving and guide patient education.     

Addressing health literacy through clear health communication: A training program for internal medicine residents

Objective

To develop, pilot, and test the effectiveness of a clear health communication curriculum to improve resident knowledge, attitudes, and skills regarding health literacy.

Methods

Thirty-one internal medicine residents participated in a small group curriculum that included didactic teaching, practice with a standardized patient, and individualized feedback on videotaped encounters with real patients. Outcomes were assessed using a pre-post survey and a communication skills checklist.

Results

Mean knowledge scores increased significantly from 60.3% to 77.6% (p < 0.001). Residents also reported increased familiarity with the concept of health literacy (mean response 3.2 vs. 4.5 on a 5 point scale), importance placed on health literacy (4.2 vs. 4.9), frequency of considering health literacy in patient care (3.3 vs. 4.0), and confidence in communicating with low literacy patients (3.3 vs. 4.1) (all p < 0.001). Use of plain language increased significantly from 33% to 86% (p = 0.023). There were nonsignificant increases in the use of teach-back (0–36%, p = 0.116) and encouraging questions (0–14%, p = 0.502).

Conclusion

Training in clear health communication improves resident knowledge, attitudes, and skills regarding health literacy.

Practice implications

The increased use of clear health communication techniques can significantly improve the care and outcomes of vulnerable patients with limited health literacy.     

Low IL10 serum levels as key factor for predicting the sustained virological response to IFNα/ribavirin in Brazilian patients with HCV carrying IL28B CT/TT genotype

Propose

IL28B polymorphisms rs12979860 CC genotype was associated to protection of HCV infection and sustained virological response (SVR) in HCV infected patients treated with pegIFNα/ribavirin (IFNα/RIB), however, this polymorphism frequency varies depending on genetic components. Studies with larger number of Brazilian individuals, determining IL28B polymorphisms is lacking. Regarding to treatment response, the levels of IL10 seem to influence response to IFNα/RIB therapy. Thus, the IL28B polymorphism frequency was investigated in health controls and infected HCV patients, as well as, in patients who reach SVR vs Non-SVR. Also, to gain insight into the interplay between IL28B genotypes, IL10 levels and therapy response, a subgroup of genotyped HCV patients SVR and Non-SVR were analyzed regarding the IL10 production.

Methods

It was enrolled 487 HCV infected patients and 234 healthy individuals. Patients with response to IFNα/RIB were classified as SVR (n = 81) and Non-SVR (n = 123). TAQMAN probes were used for genotyping the SNP rs12979860, resulting in CC, CT or TT genotypes. In one hundred one patients, the levels IL10 were measured at week 4 of IFNα/RIB.

Results

CC genotype was associated to SVR (p = 0.029) and its frequency was higher in healthy individuals vs patients (p = 0.02). Patients carrying CT/TT with IL10 < 10 pg/mL, had a chance of 2.72 to achieve SVR in multivariate model (p = 0.043).

Conclusion

CC genotype was associated to SVR and protection to HCV infection. Moreover, IL28B genotyping and IL10 serum levels could be further explored as a useful algorithm for identify the CT/TT SVR patients.     

Haplotypes of the IL-1 gene cluster are associated with gastroesophageal reflux disease and Barrett’s esophagus

Objectives

Gastroesophageal reflux (GERD) is a one of the major public health problem that can lead to reflux esophagitis (RE), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). The aim of our study was to determine the impact of IL-1 gene polymorphisms on the development of GERD, RE and BE.

Methods

Three hundred and thirty-three Czech patients with gastroesophageal reflux and 165 healthy controls were included in this case-control study. Four polymorphisms in the genes of the IL-1 cluster [IL-1A(-889C/T), IL-1B(−511C/T), IL-1B(+3953C/T), and IL-1RN(VNTR)] were analyzed.

Results

Significant differences were found in IL-1RN 1/2 genotype between patients with GERD/RE and controls and in IL-1B+3953 T allele between patients with BE and healthy subjects. In addition, complex analysis revealed differences in IL-1 haplotype frequencies between the groups. Specifically, the haplotype TCCL was significantly more frequent (p = 0.016) in GERD patients than in controls and the haplotype CCCL more frequent (p = 0.008) in RE patients than in controls. However, in patients with BE, frequency of haplotype TCTL was lower (p = 0.05) and haplotypes CTCL and TCCL were higher (p = 0.03 and p = 0.02) in comparison with the controls.

Conclusions

Our results suggest that IL-1 haplotypes may be associated with susceptibility to GERD, RE and BE.