Association between IGF1 gene single nucleotide polymorphism (rs5742612) and adolescent idiopathic scoliosis: a meta-analysis

Purpose

Insulin-like growth factor 1 (IGF1) gene single nucleotide polymorphism (rs5742612) has been associated with adolescent idiopathic scoliosis (AIS) in several studies with limited sample size and inconsistent outcomes. So we perform this meta-analysis to assess the precise association between IGF1 gene single nucleotide polymorphism (rs5742612) and AIS.

Methods

We systematically searched Pubmed, Embase, Web of Science and Cochrane Library up to January 19, 2016 to obtain relevant studies using our research strategy. Four articles all belonging to case–control studies were included in our meta-analysis.

Results

A total of four studies containing 763 cases and 559 controls satisfied the inclusion criteria after judgment by two reviewers. No significant associations were detected between IGF1 gene single nucleotide polymorphism (rs5742612) and AIS (T vs. C, OR = 1.10, 95 % CI 0.91–1.34, p = 0.32; TT vs. CC: OR = 1.28, 95 % CI 0.82–2.02, p = 0.28; TC vs. CC: OR = 1.29, 95 % CI 0.82–2.06, p = 0.27; TT/TC vs. CC: OR = 1.28, 95 % CI 0.83–1.98, p = 0.27; TT vs. TC/CC: OR = 1.06, 95 % CI 0.82–1.36, p = 0.66).

Conclusions

IGF1 gene single nucleotide polymorphism (rs5742612) is not significant associated with susceptibility to AIS in either Asian or Caucasian populations. However, IGF1 gene rs5742612 may be associated with severity of AIS. Further studies with larger sample size and different population groups involving the relationship are required to confirm the potential association.

     

Lack of association between suppressor of cytokine signaling-3 gene polymorphism and susceptibility and curve severity of adolescent idiopathic scoliosis

Purpose

To explore whether the suppressor of cytokine signaling-3 (SOCS3) gene polymorphisms are associated with the susceptibility and abnormal growth pattern of adolescent idiopathic scoliosis (AIS).

Methods

Three hundred and ninety eight AIS girls aged 10–18 years old were enrolled, and 367 age-matched healthy girls were recruited as controls. Only patients who had Cobb angles larger than 20º were included in this study. Anthropometric parameters including body weight, height, and body mass index (BMI) were measured for AIS girls. Rs4969198 was selected as tagSNP to cover all of the related polymorphisms on SOCS3. Genotyping was performed using PCR-based Invader assay with the probe sets designed and synthesized by third wave. The genotyping results were read with an ABI PRISM7900HT sequence detection system (Applied Biosystems, Foster City, CA). A subgroup of 322 skeletally mature AIS patients who did not received bracing or any other conservative treatment previously were analyzed to define the contribution of rs4969168 on curve severity, body height, body weight, and BMI.

Results

Rs4969198 was successfully genotyped. No significant difference of genotype frequencies from the Hardy–Weinberg equilibrium (HWE) test was noted for the AIS patients or the normal controls. Neither the genotype nor the allele frequencies of rs49691968 were significantly different between the AIS patients and the normal controls. Rs4969168 was not found to be associated with age, curve severity of scoliosis, and body height. AIS patients with AA genotype had significantly higher body weight and BMI than the patients with AG and GG genotype (P = 0.014).

Conclusions

The SOCS3 gene polymorphisms are not associated with the occurrence of AIS, but the gene polymorphism (rs4969168) is associated with abnormal growth pattern of AIS, indicating that SOCS3 gene might be a disease-modifying gene of AIS.     

Body composition in adolescent idiopathic scoliosis

Study design

A controlled prospective cross-sectional case study.

Objective

To investigate body mass index (BMI) and corporal composition in girls with adolescent idiopathic scoliosis (AIS) and compare them with a normal population matched by sex and age.

Summary and background data

There is controversy as to whether there are real anthropometric alterations in patients with AIS. Relative to the weight or the BMI, some studies find differences and other studies do not detect them. AIS and anorexia nervosa (AN) make their debut during adolescence and both may be associated with an alteration of their subjective physical perception. Some authors propose a link between AIS and AN supported both by an alteration of physical perception and lower BMI. No studies on body composition in AIS have been published.

Methods

Adolescent idiopathic scoliosis patient surgery candidates during 2008 were studied. Body composition was evaluated using the bioelectrical impedance analysis (Bodystat, Isle of Man, UK). A study population of more than 5,000 patients that was published by Kyle et al. (Nutrition 17:534–541, 2001) was chosen as a control (group 1). Another control group (group 2) of healthy volunteers matched by sex and age was selected among a school age and university population in Barcelona, Spain. A variance analysis was used to analyze differences between the mean values of the control group 1, the European control group, and the AIS patient surgery candidates (Epiinfo 6.2001). Comparisons between the AIS patients and control group 2 were performed with the T Student test of unpaired samples using the SPSS 15.0 (Statistical Package Social Science) software.

Results

Twenty-seven women with a mean age of 17.4 years. BMI was 18.9 kg/m² (SD 1.7; 95 % CI 18.31–19.73). In the variance analysis, a significant difference between AIS and group 1 in BMI was observed (21.0 vs. 18.9, p = 0.000004); fat-free mass (FFM = 42.6 vs. 38.9, p = 0.0000009) and fat mass (FM = 15.6 vs. 13.7, p = 0.03). Significant differences in BMI (22.13 vs. 18.9, p = 0.001; 95 % CI difference 1.85–4.60), fat mass index (FMi = 7.17 vs. 4.97, p = 0.000; 95 % CI difference 1.36–3.05) and fat-free mass index (FFMi = 14.95 vs. 13.09, p = 0.001; 95 % CI difference 0.26–1.86) between AIS and group 2 were also seen.

Conclusion

The conclusion is that there is a real alteration of body composition in AIS. The BMI, FFMi and FMi are lower than in the general population in the series under study.     

Collagen type III alpha 1 polymorphism (rs1800255, COL3A1 2209 G>A) assessed with high-resolution melting analysis is not associated with pelvic organ prolapse in the Dutch population

Introduction and hypothesis

The rs1800255, COL3A1 2209 G>A polymorphism in the alpha 1 chain of collagen type III has been associated with an increased risk of pelvic organ prolapse (POP). In one of our previous studies however, polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) misdiagnosed rs1800255, COL3A1 2209 G>A in 6 % of cases. The high-resolution melting (HRM) analysis on the contrary obtained a 100 % accordance for this specific polymorphism and was used in the present study to validate this risk factor for POP.

Methods

In this case–control study, women with and without symptoms of POP were included and compared. DNA was extracted from blood samples. HRM analysis was used to assess for the presence of the homozygous rs1800255. Groups were compared using the Pearson chi-square, Mann–Whitney, and t tests. The discrepancy between HRM and PCR-RFLP results was investigated using PCR-RFLP results available from our previous study.

Results

The study included 354 women: 272 patients with POP and 82 controls; 18 (7 %) cases versus 3 (4 %) controls had a homozygous rs1800255, COL3A1 2209 G>A polymorphism (odds ratio 1.9, 95 % confidence interval 0.5–6.9, compared to the wild type), and thus no association between POP and the homozygous polymorphism could be demonstrated. A discrepancy between HRM and PCR-RFLP results was found in 8 % of the samples.

Conclusions

The previously found statistically significant association between the rs1800255, COL3A1 2209 G>A polymorphism as measured with PCR-RFLP and POP could no longer be demonstrated. This raises concerns regarding the results of other association studies using PCR-RFLP.     

Genetic polymorphisms on 8q24.1 and 4p16.3 are not linked with urothelial carcinoma of the bladder in contrast to their association with aggressive upper urinary tract tumours

Purpose

Bladder urothelial carcinoma (bladder-UC) displays distinct genotypic differences compared to upper tract UC (UTUC). We recently reported specific 8q24 SNP variants confer susceptibility to UTUC and aggressive disease features. Herein, we evaluate a bladder-UC cohort to see whether similar polymorphisms are linked similarly same way with disease risk and aggressiveness.

Methods

231 bladder-UC patients and 261 benign controls were matched for gender, age, ethnicity and smoking habits. We retrospectively retrieved information on tumour stage, grade, size, multiplicity, carcinoma in situ and tumour number. DNA was extracted from paraffin-embedded primary bladder-UC samples and blood of benign controls. Genotyping of rs9642880[T] (8q24.1) and rs798766[T] (4p16.3) was performed using commercially available Taqman^® assays and the ABI? 7000 Sequence Detector.

Results

Using a case–control analysis, bladder-UC risk was increased in individuals carrying the T/T genotype of rs9642880 [OR = 1.72 (95 % CI 1.1–2.8); p = 0.028] and rs798766 [OR = 1.84 (95 % CI 0.9–2.3); p = 0.01]. When analysing parameters of bladder-UC aggressiveness, the T/T genotypes for rs9642880 and rs798766 were not found to be associated with either grade [OR = 0.89 (95 % CI 0.52–1.32; p = 0.68) and OR = 0.95 (95 % CI 0.58–1.48; p = 0.61), respectively] or pathological stage [OR = 0.79 (95 % CI 0.42–1.48; p = 0.46) and OR = 0.90 (95 % CI 0.49–1.61; p = 0.72), respectively]. SNP variability of rs9642880[T] and rs798766[T] is associated with an increased risk of bladder-UC but we did not find an association with disease aggressiveness as we did previously for UTUC.

Conclusions

This is further evidence of the distinct genetic differences that exist between bladder-UC and UTUC, and it is not possible to extrapolate results of genetic studies between these two urothelial disease entities.     

Meta-Analysis of Efficacy and Safety of Fast-Track Surgery in Gastrectomy for Gastric Cancer

Background

Fast-track surgery (FTS) is a promising program for surgical patients and has been applied to several surgical diseases. FTS is much superior to conventional perioperative care. Our aim was to evaluate and compare the safety and efficacy of FTS and conventional perioperative care for patients undergoing gastrectomy using a systematic review.

Methods

We searched the literature in PubMed, SCOPUS, and EMBASE up to November 2013. No language restriction was applied. Weighted mean differences (WMDs) and odds ratios (ORs) with their 95 % confidence intervals (CIs) were used for analysis by a fixed or a random effects model according to the heterogeneity assumption.

Results

In the present meta-analysis, we included five randomized controlled trials and one controlled clinical trial from five studies. Compared with conventional care, FTS shortened the duration of flatus (WMD ?21.08; 95 % CI ?27.46 to ?14.71, z = 6.48, p < 0.00001 in the open surgery group; WMD ?8.20; 95 % CI ?12.87 to ?3.53, z = 3.44, p = 0.0006 in the laparoscopic surgery group), accelerated the decrease in C-reactive protein (WMD ?15.56; 95 % CI 21.28 to 9.83, z = 5.33, p < 0.00001), shortened the postoperative stay (WMD ?2.00; 95 % CI ?2.69 to ?1.30, z = 5.64, p < 0.00001), and reduced hospitalization costs (WMD ?447.72; 95 % CI ?615.92 to ?279.51, z = 5.22, p < 0.00001). FTS made no significant difference in operation times (p = 0.93), intraoperative blood loss (p = 0.79), or postoperative complications (p = 0.07).

Conclusions

Based on current evidence, the FTS protocol was feasible for gastric cancer patients who underwent gastrectomy (distal subtotal gastrectomy, proximal subtotal gastrectomy, or radical total gastrectomy) via open or laparoscopic surgery. Larger studies are needed to validate our findings.     

Polymorphisms in Apoptosis-Related Genes and Survival of Patients with Early-Stage Non-Small-Cell Lung Cancer

Purpose

This study was conducted to determine the association between single-nucleotide polymorphisms (SNPs) in apoptosis-related genes and survival outcomes of patients with early-stage non-small-cell lung cancer (NSCLC).

Methods

Three hundred ten consecutive patients with surgically resected NSCLC were enrolled. Twenty-five SNPs in 17 apoptosis-related genes were genotyped by a sequenome mass spectrometry-based genotyping assay. The genotype associations with overall survival (OS) and disease-free survival (DFS) were analyzed.

Results

Three SNPs (TNFRSF10B rs1047266, TNFRSF1A rs4149570, and PPP1R13L rs1005165) were significantly associated with survival outcomes on multivariate analysis. When the three SNPs were combined, OS and DFS were decreased as the number of bad genotypes increased (P _trend for OS and DFS = 7 × 10^?5 and 1 × 10^?4, respectively). Patients with one bad genotype, and patients with two or three bad genotypes had significantly worse OS and DFS compared with those with no bad genotypes [adjusted hazard ratio (aHR) for OS = 2.27, 95% confidence interval (CI) = 1.22–4.21, P = 0.01, aHR for DFS = 1.74, 95% CI = 1.08–2.81, P = 0.02; aHR for OS = 4.11, 95% CI = 2.03–8.29, P = 8 × 10^?5; and aHR for DFS = 2.89, 95% CI = 1.64–5.11, P = 3 × 10^?4, respectively].

Conclusion

Three SNPs in apoptosis-related genes were identified as possible prognostic markers of survival in patients with early-stage NSCLC. The SNPs, and particularly their combined genotypes, can be used to identify patients at high risk for poor disease outcome.     

High Volumetric Breast Density Predicts Risk for Breast Cancer in Postmenopausal,but not Premenopausal,Korean Women

Purpose

We investigated the association between mammographic breast density and breast cancer risk in Korean women according to menopausal status and breast cancer subtypes.

Methods

We enrolled 677 patients diagnosed with breast cancer and 1,307 healthy controls who participated in screening mammography at the National Cancer Center. Breast density was estimated using volumetric breast composition measurement.

Results

Of the total population, 1,156 (58.3 %) women were postmenopausal. The risk of breast cancer increased progressively with the increment of volumetric density grade (VDG) in postmenopausal women (p < 0.001). High breast density (VDG 4) was significantly associated with breast cancer compared with low breast density (VDG 1/2) regardless of body mass index. However, the association with parity and history of hormone replacement therapy (HRT) was only found in those with ≥2 children and those not receiving HRT. Breast density was positively associated with breast cancer risk regardless of histologic grade, tumor size, lymph node involvement, Ki67 index, and hormone receptor status. The association was more prominent in human epidermal growth factor receptor 2 (HER2)-positive tumors (VDG 1/2 vs. VDG 4 for HER2 normal, odds ratio [OR] 2.21, 95 % confidence interval [CI] 1.28–3.83, p < 0.001; for HER2 positive, OR 8.63, 95 % CI 3.26–22.83, p = 0.001; P _{heterogeneity} = 0.030). However, no significant association was found between breast density and breast cancer risk in premenopausal women except for those with large-sized tumors (>2 cm) and a Ki67 index >15 %.

Conclusion

High volumetric breast density is significantly associated with the risk of breast cancer in postmenopausal women; however, these relationships were not found in premenopausal women.     

Association between non-alcoholic fatty liver disease and chronic kidney disease in population with prediabetes or diabetes

Purpose

The relationship between chronic kidney disease (CKD) and non-alcoholic fatty liver disease (NAFLD) in population with diabetes remains controversial. Our current study aimed to explore the association between NAFLD and CKD in population with prediabetes or diabetes.

Methods

A cross-sectional study was conducted in Zhuhai city from June to October 2012. A total of 190 out of 334 participants with prediabetes or diabetes were enrolled in this study. CKD was defined as estimated GFR <60 ml/min per 1.73 m² and/or albumin-to-creatinine ratio ≥30 mg/g. NAFLD was diagnosed on the basis of ultrasonographic and excluded fatty liver disease caused by other reasons such as drinking. The association between NAFLD and CKD was then analyzed using SPSS (version 19.0).

Results

Subjects with NAFLD were more likely with a higher urinary albumin-to-creatinine ratio (P < 0.001). CKD were common among patients with NAFLD than those without NAFLD (P < 0.05). NAFLD was significantly associated with CKD (P < 0.05) in the unadjusted analyses as well as after adjustment for potential confounders. The unadjusted odd ratio and adjusted odd ratio for CKD were 2.25 (95 % CI 1.07–4.77, P = 0.034) and 2.68 (95 % CI 1.12–6.01, P = 0.016). When further adjusted for hypertension, serum high-density lipoprotein and serum fasting glucose, the association of NAFLD with CKD was still significant (OR 2.78, 95 % CI 1.03–7.52, P = 0.044).

Conclusions

Our current study suggests that ultrasound-diagnosed NAFLD is associated with CKD among population with prediabetes or diabetes.     

A prospective randomized controlled study on the treatment outcome of SpineCor brace versus rigid brace for adolescent idiopathic scoliosis with follow-up according to the SRS standardized criteria

Purpose

SpineCor is a relatively innovative brace for non-operative treatment of adolescent idiopathic scoliosis (AIS). However, the effectiveness of SpineCor still remains controversial. The objective of the current study was to compare the treatment outcomes of SpineCor brace with that of rigid brace following the standardized Scoliosis Research Society (SRS) criteria on AIS brace study.

Methods

Females subjects with AIS and aged 10–14 were randomly allocated into two groups undergoing treatment of SpineCor (S Group, n = 20) or rigid brace (R Group, n = 18). During SpineCor treatment, patients who had curve progression of >5° would be required to switch to rigid brace treatment. The effectiveness of the two brace treatments was assessed using the SRS standardized criteria.

Results

Before skeletal maturity, 7 (35.0 %) patients in the S Group and 1 (5.6 %) patient in the R Group had curve progression >5° (P = 0.026). At skeletal maturity, 5 of the 7 (71.4 %) patients who failed with SpineCor bracing showed control from further progression by changing to rigid bracing. At the latest follow-up with a mean duration of 45.1 months after skeletally maturity, 29.4 % of patients who were successfully treated by rigid brace showed further curve progression beyond skeletal maturity, versus 38.5 % of patients in the SpineCor group (P > 0.05). For both groups, the primary curves were slightly improved at the time of brace weaning, but additionally increased at the latest follow-up, with a rate of 1.5° per year for post-maturity progression.

Conclusions

Curve progression rate was found to be significantly higher in the SpineCor group when compared with the rigid brace group. Changing to rigid bracing could control further curve progression for majority of patients who previously failed with SpineCor bracing. For both SpineCor and rigid brace treatments, 30–40 % of patients who were originally successfully treated by bracing would exhibit further curve progression beyond skeletal maturity. The post-maturity progression rate was found to be 1.5° per year in the current study, which was relatively greater than those reported before.     

The exponential function transforms the Abbreviated Injury Scale,which both improves accuracy and simplifies scoring

Purpose

We present here the exponential function which transforms the Abbreviated Injury Scale (AIS). It is called the Exponential Injury Severity Score (EISS), and significantly outperforms the venerable but dated New Injury Severity Score (NISS) and Injury Severity Score (ISS) as a predictor of mortality.

Methods

The EISS is defined as a change of AIS values by raising each AIS severity score (1–6) by 3 taking a power of AIS minus 2 and then summing the three most severe injuries (i.e., highest AIS), regardless of body regions. EISS values were calculated for every patient in two large independent data sets: 3,911 and 4,129 patients treated during a 6-year period at the Class A tertiary hospitals in China. The power of the EISS to predict mortality was then compared with previously calculated NISS values for the same patients in each of the two data sets.

Results

We found that the EISS is more predictive of survival [Zhejiang: area under the receiver operating characteristic curve (AUC): NISS = 0.932, EISS = 0.949, P = 0.0115; Liaoning: AUC: NISS = 0.924, EISS = 0.942, P = 0.0139]. Moreover, the EISS provides a better fit throughout its entire range of prediction (Hosmer–Lemeshow statistic for Zhejiang: NISS = 21.86, P = 0.0027, EISS = 13.52, P = 0.0604; Liaoning: NISS = 23.27, P = 0.0015, EISS = 15.55, P = 0.0164).

Conclusions

The EISS may be used as the standard summary measure of human trauma.     

Associations of polymorphisms in the SOST gene and bone mineral density in postmenopausal Chinese Women

Summary

The bone mineral density (BMD) of a total of 1,379 healthy postmenopausal Chinese women was measured. Ten tagging SNPs of the sclerostin (SOST) gene were genotyped. Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in postmenopausal Chinese women.

Introduction

The purpose of the study was to determine the associations between polymorphisms of SOST gene and BMD in postmenopausal Chinese women.

Methods

A total of 1,379 independent healthy postmenopausal Chinese women including 703 in our previous study were recruited. The BMD of the lumbar spine 1–4 (L1–4) and left proximal femur including total hip and femoral neck were measured by dual-energy X-ray absorptiometry. Ten tagging SNPs (rs1234612, rs1513670, rs1634330, rs1708635, rs2023794, rs7220711, rs74252774, rs851057, rs851058, and rs865429) of the SOST gene were genotyped.

Results

The rs2023794 and rs74252774 and the haplotype ACCATTCT of SOST gene were associated with age and body mass index (BMI) adjusted L1–4 BMD (P values were 0.010, 0.007, and 0.007, respectively) even after performing the Bonferroni multiple-significance-test correction. There was a clear trend in these regions that the CC genotype of the rs2023794 and the TT genotype of the rs74252774 have higher BMD values than other genotypes. The contributions of the rs2023794 and rs74252774 to the phenotypic variation of L1–4 BMD were 0.6 and 0.7 %, respectively. We failed to find any association between the 10 SNPs and 6 haplotypes of the SOST gene and BMD at the hip site in this study.

Conclusions

Our results suggest that the polymorphisms of the rs2023794 and rs74252774 in the SOST gene were associated with BMD of the lumbar spine in a large sample of postmenopausal Chinese women.     

Usefulness of the neutrophil/lymphocyte ratio measured preoperatively as a predictor of peritoneal metastasis in patients with advanced gastric cancer

Purpose

The prognosis for gastric cancer patients with peritoneal metastasis is poor. Many studies have reported that the neutrophil/lymphocyte ratio (NLR) might be useful to predict the degree of progression of gastric cancer. In this study, we attempted to evaluate whether the NLR and other related laboratory parameters might be reliable predictors of the presence of peritoneal metastasis in patients with advanced gastric cancer.

Methods

The data of 359 patients who underwent gastric surgery between June 2008 and December 2011 were reviewed. A retrospective analysis of the preoperative blood data in relation to the presence of peritoneal metastasis was carried out.

Results

An increased serum C-reactive protein level (P = 0.022), APTT (P = 0.017) and NLR (P < 0.001), and a decreased serum Alb (P = 0.014) were significantly related to the presence of peritoneal metastasis. A multivariate analysis showed that a NLR >2.37 (OR = 2.59, 95 % CI = 1.38–4.93, P = 0.003) and clinical T4 stage (OR = 4.36, 95 % CI = 2.33–8.24, P < 0.001) were independent predictors of the presence of peritoneal metastasis.

Conclusion

Our results suggest that the preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis in patients with advanced gastric cancer.     

Residents’ Engagement and Empathy Associated With Their Perception of Faculty’s Teaching Performance

Background

Faculty members rely on residents’ feedback about their teaching performance. The influence of residents’ characteristics on evaluations of faculty is relatively unexplored. We aimed to evaluate the levels of work engagement and empathy among residents and the association of both characteristics with their evaluation of the faculty’s teaching performance.

Methods

A multicenter questionnaire study among 271 surgery and gynecology residents was performed from September 2012 to February 2013. Residents’ ratings of the faculty’s teaching performance were collected using the system for evaluation of teaching quality (SETQ). Residents were also invited to fill out standardized measures of work engagement and empathy using the short Utrecht Work Engagement Scale and the Jefferson Scale of Physician Empathy, respectively. Linear regression analysis using generalized estimating equations to evaluate the association of residents’ engagement and empathy with residents’ evaluations of teaching performance.

Results

Overall, 204 (75.3 %) residents completed 1814 SETQ evaluations of 302 faculty, and 143 (52.8 %) and 140 (51.7 %) residents, respectively, completed the engagement and empathy measurements. The median scores of residents’ engagement and empathy were 4.56 (scale 0–6) and 5.55 (scale 1–7), respectively. Higher levels of residents’ engagement (regression coefficient b = 0.128; 95 % confidence interval (CI) 0.072–0.184; p < 0.001) and empathy (b = 0.113; 95 % CI 0.063–0.164; p < 0.001) were associated with higher faculty teaching performance scores.

Conclusions

Residents’ engagement and empathy appear to be positively associated with their evaluation of the faculty’s performance. A possible explanation is that residents who are more engaged and can understand and share others’ perspectives stimulate and experience faculty’s teaching better than others.     

Coffee consumption and urologic cancer risk: a meta-analysis of cohort studies

Objectives

Controversial results were reported among several epidemiologic studies on the relationship between coffee consumption and urologic cancer risk. We, therefore, conducted this meta-analysis to clarify these associations.

Methods

Electronic databases including Pubmed, Embase and Cochrane library were searched between January 1966 and August 2013 for eligible studies. Pooled relative risk (RR) and its 95 % confidence interval (CI) were calculated. All P values are two tailed.

Results

Thirteen cohorts were eligible for inclusion. As to prostate cancer (PCa), significant reverse association was found among highest versus none/lowest analysis with acceptable heterogeneity (RR 0.86, 95 % CI 0.79–0.95; I ² 25 %, P value for heterogeneity: 0.221). A pooled RR which assessed advanced PCa was 0.73 (with 95 % CI 0.50–1.07), and a slight stronger reverse association was found in fatal PCa. However, a slight insignificant reverse association, basing on 8 studies with 9 outcomes, was found in dose–response analysis (RR 0.98, 95 % CI 0.93–1.03). For kidney and bladder cancer, insignificant associations were found in both highest versus none/lowest analyses and dose–response analyses.

Conclusions

Our findings suggest that coffee consumption may reduce the risk of PCa. No associations were found with both bladder and kidney cancer. Further well-designed large-scaled cohort studies are warranted to provide more definitive conclusions.     

Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients

Purpose

The role of tonsillectomy in the treatment of IgA nephropathy in Caucasian patients is controversial.

Methods

A retrospective cohort study was conducted in 264 patients with biopsy-proven primary IgA nephropathy to examine the association between tonsillectomy and long-term renal survival, defined as the incidence of estimated glomerular filtration rates (eGFRs) of ≤30 ml/min/1.73 m² or end-stage renal disease (the composite of initiation of dialysis treatment or renal transplantation). The association of tonsillectomy with renal end-points was examined using the Kaplan–Meier method and Cox models.

Results

One-hundred and sixty-six patients did not undergo tonsillectomy (Group I, follow-up 130 ± 101 months) and 98 patients underwent tonsillectomy (Group II, follow-up 170 ± 124 months). The mean renal survival time was significantly longer for both end-points between those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points.

Conclusion

Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed.     

Genetic Variants in Genes of Tricarboxylic Acid Cycle Key Enzymes Predict Postsurgical Overall Survival of Patients with Hepatocellular Carcinoma

Background

Metabolic reprogramming is a hallmark of cancer, including the alterations of activity and expression in tricarboxylic acid (TCA) cycle key enzymes. However, the significance of single nucleotide polymorphisms (SNPs) in genes encoding these key enzymes has not been investigated in hepatocellular carcinoma (HCC).

Methods

In this study, 17 SNPs in seven genes encoding three TCA cycle enzyme families (SDH, FH, and IDH) were genotyped in 492 HCC patients with surgical treatment and their association with overall survival (OS) was analyzed.

Results

Five SNPs in four genes were identified to be associated with OS in HCC patients. Among them, rs3935401 in the 3′ untranslated region of SDHC exhibited the most significant association (P < 0.001). The unfavorable genotype of these five SNPs showed a significant accumulative effect on the prognosis of HCC patients, with a P for trend of <0.001. Furthermore, the haplotype group consisting of wild type in rs4131826 and variant in rs3935401 was significantly associated with increased risk of death in HCC patients. Survival tree analysis indicated that variant genotype of rs3935401 was the primary risk factor contributing to the prediction of OS in HCC patients.

Conclusions

SNPs in TCA cycle key enzyme genes may serve as potential biomarkers to predict the OS in HCC patients.     

Replication study for the association of 3 SNP loci identified in a genome-wide association study for diabetic nephropathy in European type 1 diabetes with diabetic nephropathy in Japanese patients with type 2 diabetes

Background

A recent genome-wide association study for diabetic nephropathy in European type 1 diabetes identified 3 candidate loci for diabetic nephropathy. In this study, we examined the association of the 3 single nucleotide polymorphism (SNP) loci with susceptibility to diabetic nephropathy in Japanese subjects with type 2 diabetes.

Methods

We genotyped 3 SNPs, rs7583877 in AFF3, rs12437854 in the RGMA-MCTP2 locus and rs7588550 in ERBB4, for 2,300 Japanese patients with type 2 diabetes [initial study, 1,055 nephropathy cases with overt proteinuria or with end-stage renal disease (ESRD) and 1,245 control patients with normoalbuminuria]. The association of these SNPs with diabetic nephropathy was examined by using a logistic regression analysis.

Results

We observed a significant association of rs7588550 in ERBB4 with diabetic nephropathy in the Japanese patients with type 2 diabetes, although the effect direction was not consistent with that in the European study [p = 0.0126, odds ratio (OR) = 0.79, 95 % confidence interval (CI): 0.65–0.95]. We further examined the association of rs7588550 with diabetic nephropathy in an independent Japanese cohort (596 nephropathy cases and 311 controls) and observed the same trend of the association with the initial study. We did not observe any association of the remaining 2 SNP loci with diabetic nephropathy in the present Japanese sample.

Conclusion

The association of SNP loci derived from GWAS in European type 1 diabetes with diabetic nephropathy was not replicated in the Japanese patients with type 2 diabetes, although the ERBB4 locus may have some effect also in Japanese type 2 diabetes.     

Are Copy Number Variants Associated With Adolescent Idiopathic Scoliosis?

Background

Adolescent idiopathic scoliosis (AIS) is a complex genetic disorder that causes spinal deformity in approximately 3% of the population. Candidate gene, linkage, and genome-wide association studies have sought to identify genetic variation that predisposes individuals to AIS, but the genetic basis remains unclear. Copy number variants are associated with several isolated skeletal phenotypes, but their role in AIS, to our knowledge, has not been assessed.

Questions/Purposes

We determined the frequency of recurrent copy number rearrangements, chromosome aneuploidy, and rare copy number variants in patients with AIS.

Methods

Between January 2010 and August 2014, we evaluated 150 patients with isolated AIS and spinal curvatures measuring 10° or greater, and 148 agreed to participate. Genomic copy number analysis was performed on patients and 1079 control subjects using the Affymetrix^® Genome-wide Human SNP Array 6.0. After removing poor quality samples, 143 (97%) patients with AIS were evaluated for copy number variation.

Results

We identified a duplication of chromosome 1q21.1 in 2.1% (N = 3/143) of patients with AIS, which was enriched compared with 0.09% (N = 1/1079) of control subjects (p = 0.0057) and 0.07% (N = 6/8329) of a large published control cohort (p = 0.0004). Other notable findings include trisomy X, which was identified in 1.8% (N = 2/114) of female patients with AIS, and rearrangements of chromosome 15q11.2 and 16p11.2 that previously have been associated with spinal phenotypes. Finally, we report rare copy number variants that will be useful in future studies investigating candidate genes for AIS.

Conclusions

Copy number variation and chromosomal aneuploidy may contribute to the pathogenesis of adolescent idiopathic scoliosis.

Clinical Relevance

Chromosomal microarray may reveal clinically useful abnormalities in some patients with AIS.     

The comparison of instrumented and non-instrumented fusion in the treatment of lumbar spondylolisthesis: a meta-analysis

Purpose

This meta-analysis compared whether fusion with or without instrumentation to treat this disease differed with respect to patient-centered outcomes.

Methods

Medline, Cochrane, EMBASE, Google Scholar data bases were searched for randomized control trials that investigated patients with severe chronic lower back pain resulting from localized lumbar or lumbosacral instability caused by either isthmic spondylolisthesis or degenerative spondylolisthesis. Included randomized studies reported quantitative outcomes for low back pain and functional recovery. The primary outcome was the improvement of function and the secondary outcomes were the improvement of pain, patients’ satisfactory level, and the fusion rate.

Results

A significantly lower function change in patients with instrumented compared with non-instrumented from baseline (pooled standardized mean difference; ?1.02 (95 % CI ?1.76 to ?0.27); Z ?2.67; (P = 0.008)]. There was no significant pain change for patients with instrumented compared with that of non-instrumented from baseline [pooled standardized mean difference; ?0.07 (95 % CI ?1.25 to 1.12); Z ?0.11; (P = 0.913)]. There was no significant difference in satisfactory level for patients with instrumented compared with that of non-instrumented [pooled OR; 2.36 (95 % CI 0.91–6.11); Z 1.76; (P = 0.078)]. There was significantly higher fusion rate for patients with instrumented compared with that of non-instrumented [pooled OR; 3.28 (95 % CI 2.22–4.85); Z 5.96; (P < 0.001)].

Conclusions

This meta-analysis found that inclusion of fusion surgery with instrumentation provided no benefit as evaluated by patient-reported outcomes in patients with lumbar spondylolisthesis.

Level of evidence

Not applicable.