Association of INSIG2 Polymorphism with Overweight and LDL in Children

Background

Dyslipidemia and overweight are common issues in children. Identifying genetic markers of risk could lead to targeted interventions. A polymorphism of SNP rs7566605 near insulin-induced gene 2 (INSIG2) has been identified as a strong candidate gene for obesity, through its feedback control of lipid synthesis.

Objective

To identify polymorphisms in INSIG2 which are associated with overweight (BMI ≥ 85% for age) and dyslipidemia in children. Hypothesis: The C allele of rs7566605 would be significantly associated with BMI and LDL.

Design/Methods

We genotyped 15 SNPs in/near INSIG2 in 1,058 healthy children (53% non-Hispanic white (NHW), 37% overweight) participating in a school based study. Genotype was compared with BMI and lipid markers, adjusting for age, gender, and puberty.

Results

We found a significant association between the SNP rs12464355 and LDL in NHW children, p < 0.001. The G allele is protective (lower LDL). A different SNP was associated with overweight in NHW: rs17047757. SNP rs7566605 was not associated with overweight or lipid levels.

Conclusions

We identified novel genetic associations between INSIG2 and both overweight and LDL in NHW children. Polymorphisms in INSIG2 may be important in the development of obesity through its effects on lipid regulation.     

The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men

Background

The apolipoprotein E (APOE) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.

Methods

We analyzed fasting plasma lipids and genotyped the two main APOE-SNPs (rs429358 and rs7412), both located in the fourth exon of the APOE, in 4660 Caucasian middle-aged men free of cardiovascular disease.

Results

The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01–1.59).

Conclusions

This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.     

Evaluation of Multiparametric Magnetic Resonance Imaging in Detection and Prediction of Prostate Cancer

Background

Although European Society of Urogenital Radiology proposed the potential of multiparametric magnetic resonance imaging (MP-MRI) as a tool in the diagnostic pathway for prostate cancer (PCa) and published a unified scoring system named Prostate Imaging Reporting and Data System (PI-RADS version 1), these still need to be validated by real-life studies.

Objective

To evaluate the role of MP-MRI in detection and prediction of PCa.

Methods

Patients with clinical suspicion of PCa who underwent prebiopsy MP-MRI from 2002 to 2009 were recruited. MP-MRI results were retrospectively assigned as overall scores using PI-RADS by two radiologists. Patients were followed and the end point was the diagnosis of PCa. Receiver operating characteristics (ROC) curve was performed to test diagnostic efficacy of MP-MRI, under results of biopsy within three months. The cox proportional hazards model was used to identify independent variables for the detection of PCa.

Results

Finally, 1113 of the 1806 enrolled patients were included for analysis. The median follow-up was 56.0 months (1–137 mo). For 582 patients biopsied within three months, area under the curve for the detection of PCa with MP-MRI was 0.88 (95% confidence interval [CI], 0.75–1.00) in group of baseline prostate specific antigen (PSA) 0.01–4.00 ng/ml (n = 31), 0.90 (95% CI, 0.84–0.95) in PSA 4.01–10.00 ng/ml (n = 142), and 0.91 (95% CI, 0.87–0.94) in PSA >10.00 ng/ml (n = 409), respectively. In the cox model adjusted for age and baseline PSA level, for the detection rate of PCa, compared with PI-RADS 1–2 (reference), the hazard ratio was 6.43 (95% CI, 4.29–9.65) for PI-RADS 3, 18.58 (95% CI, 13.36–25.84) for PI-RADS 4–5 (p < 0.001).

Conclusions

Prebiopsy MP-MRI with PI-RADS is demonstrated as a valuable diagnostic and predictive tool for PCa.     

Predictive Value of Interferon-Lambda Gene Polymorphisms for Treatment Response in Chronic Hepatitis C

Background

IL28B gene polymorphism is the best baseline predictor of response to interferon alfa-based antiviral therapies in chronic hepatitis C. Recently, a new IFN-L4 polymorphism was identified as first potential functional variant for induction of IL28B expression. Individualization of interferon alfa-based therapies based on a combination of IL28B/IFN-L4 polymorphisms may help to optimize virologic outcome and economic resources.

Methods

Optimization of treatment outcome prediction was assessed by combination of different IL28B and IFN-L4 polymorphisms in patients with chronic HCV genotype 1 (n = 385), 2/3 (n = 267), and 4 (n = 220) infection treated with pegylated interferon alfa (PEG-IFN) and ribavirin with (n = 79) or without telaprevir. Healthy people from Germany (n = 283) and Egypt (n = 96) served as controls.

Results

Frequencies of beneficial IL28B rs12979860 C/C genotypes were lower in HCV genotype 1/4 infected patients in comparison to controls (20–35% vs. 46–47%) this was also true for ss469415590 TT/TT (20–35% vs. 45–47%). Single interferon-lambda SNPs (rs12979860, rs8099917, ss469415590) correlated with sustained virologic response (SVR) in genotype 1, 3, and 4 infected patients while no association was observed for genotype 2. Interestingly, in genotype 3 infected patients, best SVR prediction was based on IFN-L4 genotype. Prediction of SVR with high accuracy (71–96%) was possible in genotype 1, 2, 3 and 4 infected patients who received PEG-IFN/ribavirin combination therapy by selection of beneficial IL28B rs12979860 C/C and/or ss469415590 TT/TT genotypes (p<0.001). For triple therapy with first generation protease inhibitors (PIs) (boceprevir, telaprevir) prediction of high SVR (90%) rates was based on the presence of at least one beneficial genotype of the 3 IFN-lambda SNPs.

Conclusion

IFN-L4 seems to be the best single predictor of SVR in genotype 3 infected patients. For optimized prediction of SVR by treatment with dual combination or first generation PI triple therapies, grouping of interferon-lambda haplotypes may be helpful with positive predictive values of 71–96%.     

Higher Body Mass Index Increases the Risk for Biopsy-Mediated Detection of Prostate Cancer in Chinese Men

Objective

To investigate the relationship between body mass index (BMI) and prostate cancer (PCa) risk at biopsy in Chinese men.

Patients and Methods

We retrospectively reviewed the records of 1,807 consecutive men who underwent initial multicore (≥10) prostate biopsy under transrectal ultrasound guidance between Dec 2004 and Feb 2014. BMI was categorised based on the Asian classification of obesity as follows: <18.5 (underweight), 18.5–22.9 (normal weight), 23–24.9 (overweight), 25–29.9 (moderately obese), and ≥30 kg/m2 (severely obese). The odds ratios (OR) of each BMI category for risk of PCa and high-grade prostate cancer (HGPCa, Gleason score ≥4+3) detection were estimated in crude, age-adjusted and multivariate-adjusted models. Prevalence ratios and accuracies of PSA predicted PCa were also estimated across BMI groups.

Results

In total, PCa was detected by biopsy in 750 (45.4%) men, and HGPCa was detected in 419 (25.4%) men. Compared with men of normal weight, underweight men and obese men were older and had higher prostate specific antigen levels. The risk of overall PCa detection via biopsy presented an obvious U-shaped relationship with BMI in crude analysis. Overall, 50.0%, 37.4%, 45.6% 54.4% and 74.1% of the men in the underweight, normal weight, overweight, moderately obese and severely obese groups, respectively, were diagnosed with PCa via biopsy. In multivariate analysis, obesity was significantly correlated with a higher risk of PCa detection (OR = 1.17, 95%CI 1.10–1.25, P<0.001). However, higher BMI was not correlated with HGPCa detection (OR = 1.03, 95%CI 0.97–1.09, P = 0.29). There were no significant differences in the accuracy of using PSA to predict PCa or HGPCa detection across different BMI categories.

Conclusion

Obesity was associated with higher risk of PCa detection in the present Chinese biopsy population. No significant association was detected between obesity and HGPCa.     

FCRL3 Gene Polymorphisms Confer Autoimmunity Risk for Allergic Rhinitis in a Chinese Han Population

Background

Heredity and environmental exposures may contribute to a predisposition to allergic rhinitis (AR). Autoimmunity may also involve into this pathologic process. FCRL3 (Fc receptor-like 3 gene), a novel immunoregulatory gene, has recently been reported to play a role in autoimmune diseases.

Objective

This study was performed to evaluate the potential association of FCRL3 polymorphisms with AR in a Chinese Han population.

Methods

Five single-nucleotide polymorphisms of FCRL3, rs945635, rs3761959, rs7522061, rs10489678 and rs7528684 were genotyped in 540 AR patients and 600 healthy controls using a PCR-restriction fragment length polymorphism assay. Allele, genotype and haplotype frequencies were compared between patients and controls using the χ2 test. The online software platform SHEsis was used to analyze their haplotypes.

Results

This study identified three strong risk SNPs rs7528684, rs10489678, rs7522061 and one weak risk SNP rs945635 of FCRL3 in Chinese Han AR patients. For rs7528684, a significantly increased prevalence of the AA genotype and A allele in AR patients was recorded. The frequency of the GG genotype and G allele of rs10489678 was markedly higher in AR patients than those in controls. For rs7522061, a higher frequency of the TT genotype, and a lower frequency of the CT genotype were found in AR patients. Concerning rs945635, a lower frequency of the CC genotype, and a higher frequency of G allele were observed in AR patients. According to the analysis of the three strong positive SNPs, the haplotype of AGT increased significantly in AR cases (AR = 38.8%, Controls = 24.3%, P = 8.29×10-14, OR [95% CI] 1.978 [1.652~2.368]).

Conclusions

This study found a significant association between the SNPs in FCRL3 gene and AR in Chinese Han patients. The results suggest these gene polymorphisms might be the autoimmunity risk for AR.     

Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease

Objective

To replicate the associations of leukocyte telomere length (LTL) with variants at four loci and to investigate their associations with coronary heart disease (CHD) and type II diabetes (T2D), in order to examine possible causal effects of telomere maintenance machinery on disease aetiology.

Methods

Four SNPs at three loci BICD1 (rs2630578 GγC), 18q12.2 (rs2162440 GγT), and OBFC1 (rs10786775 CγG, rs11591710 AγC) were genotyped in four studies comprised of 2353 subjects out of which 1148 had CHD and 566 T2D. Three SNPs (rs12696304 CγG, rs10936601G>T and rs16847897 GγC) at the TERC locus were genotyped in these four studies, in addition to an offspring study of 765 healthy students. For all samples, LTL had been measured using a real-time PCR-based method.

Results

Only one SNP was associated with a significant effect on LTL, with the minor allele G of OBFC1 rs10786775 SNP being associated with longer LTL (β=0.029, P=0.04). No SNPs were significantly associated with CHD or T2D. For OBFC1 the haplotype carrying both rare alleles (rs10786775G and rs11591710C, haplotype frequency 0.089) was associated with lower CHD prevalence (OR: 0.77; 95% CI: 0.61–0.97; P= 0.03). The TERC haplotype GTC (rs12696304G, rs10936601T and rs16847897C, haplotype frequency 0.210) was associated with lower risk for both CHD (OR: 0.86; 95% CI: 0.75-0.99; P=0.04) and T2D (OR: 0.74; 95% CI: 0.61–0.91; P= 0.004), with no effect on LTL. Only the last association remained after adjusting for multiple testing.

Conclusion

Of reported associations, only that between the OBFC1 rs10786775 SNP and LTL was confirmed, although our study has a limited power to detect modest effects. A 2-SNP OBFC1 haplotype was associated with higher risk of CHD, and a 3-SNP TERC haplotype was associated with both higher risk of CHD and T2D. Further work is required to confirm these results and explore the mechanisms of these effects.     

Single Positive Lymph Node Prostate Cancer Can Be Treated Surgically without Recurrence

Purpose/Objectives

To investigate pN1 prostate cancer (PCa) patients treated surgically without immediate adjuvant treatment.

Materials and Methods

We analyzed the database of 2316 patients at our institution who underwent robot-assisted radical prostatectomy (RARP)/radical prostatectomy (RP) between July 2005 and November 2012. 87 patients with pN1 PCa and received no neoadjuvant and immediate adjuvant therapy were included in the study. Included pN1 PCa patients were followed up for median of 60 months. Biochemical recurrence (BCR)-free survival, metastasis-free survival (MFS), cancer specific survival (CSS), and overall survival (OS) rates were determined by using Kaplan-Meier analysis. Cox regression analysis was performed to investigate the impact of prostate-specific antigen (PSA) level, Gleason score, extraprostatic extension, seminal vesicle invasion, perineural invasion, lymphovascular invasion, positive surgical margin, tumor volume, early post-operative PSA(6 weeks), PSA nadir, lymph node yield, and number of pathologically positive lymph nodes on survival.

Results

The 5-year OS rate of patients was 86.1%, while the CSS rate was 89.6%. The metastasis-free and BCR-free survival rates were 71% and 19.1%, respectively, and each was significantly correlated with the number of positive lymph nodes on log rank tests (p = 0.004 and p = 0.039, respectively). The presence of 2 or more pathologically positive LNs (HR:2.20; 95% CI 1.30–3.72; p = 0.003) and a Gleason score ≥8 (HR: 2.40;95% CI: 1.32–4.38; p = 0.04) were significant negative predictors of BCR free survival on multivariable regression analysis. Furthermore, the presence of 2 or more positive lymph nodes (HR: 1.06; 95% CI 1.01–1.11; p = 0.029) were significant negative predictors of metastasis-free survival on multivariable regression analysis. Additionally, in the patients who had no BCR without adjuvant treatment 9 patients out of 10 (90%) had single positive LN and 5 patients out of 10 (50%) had Gleason score 7. Therefore, single positive LN, and Gleason scores ≤7 have significantly low risk of disease progression.

Conclusions

pN1 PCa patients have heterogenous clinical courses. Patients with single positive LN, and Gleason scores ≤7 have low risk of recurrence. Close observation with delayed adjuvant hormone therapy can be considered in these patients.     

A Genetic Variant in the Promoter Region of miR-106b-25 Cluster Predict Clinical Outcome of HBV-Related Hepatocellular Carcinoma in Chinese

Background

MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response, tumorigenesis and progression. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7. Our previous study showed that the A to G base change of rs999885 may provide an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster. However, it is unknown whether rs999885 is associated with prognosis of intermediate or advanced HBV-related hepatocellular carcinoma (HCC) patients.

Methods

The SNP, rs999885, was genotyped by using the TaqMan allelic discrimination Assay in 414 intermediate or advanced HCC patients. Log-rank test and Cox proportional hazard models were used for survival analysis.

Results

The variant genotypes of rs999885 were associated with a significantly decreased risk of death for intermediate or advanced HCC [additive model: adjusted hazard ratio (HR)  = 0.76,95% confidence intervals (CI)  = 0.59–0.97]. Further stepwise regression analysis suggested that rs999885 was an independently protective factor for the prognosis of HCC in the final model (additive model: adjusted HR  = 0.72, 95% CI  = 0.56–0.91, P = 0.007).

Conclusions

These findings indicate that the A to G base change of rs999885 may provide a protective effect on the prognosis of intermediate or advanced HCC in Chinese.     

Can Contemporary Patients with Biopsy Gleason Score 3+4 Be Eligible for Active Surveillance?

Introduction

We analyzed whether expansion of existing active surveillance (AS) protocols to include men with biopsy Gleason score (GS) 3+4 prostate cancer (PCa) would significantly alter pathologic and biochemical outcomes of potential candidates of AS.

Methods

Among patients who underwent radical prostatectomy at our center between 2006 and 2013, we identified 577 patients (group A) who preoperatively fulfilled at least one of 6 different AS criteria. Also, we identified 217 patients (group B) with biopsy GS 3+4 but fulfilled non-GS criteria from at least one of 6 AS criteria. Designating group C as expanded group incorporating all patients in group A and B, we compared risk of unfavorable disease (pathologic GS ≥4+3 and/or pathologic T stage ≥pT3a) and biochemical recurrence (BCR)-free survival between groups.

Results

Rates of unfavorable disease were not significantly different between patients of group A and C who met AS criteria from 5 institutions (all p>0.05), not including University of Toronto (p<0.001). Also BCR-free survivals were not significantly different between patients in group A and C meeting each of 6 AS criteria (all p>0.05). Among group B, PSAD>0.15 ng/mL/cm³ (p = 0.011) and tumor length of biopsy GS 3+4 core>4 mm (p = 0.007) were significant predictors of unfavorable disease. When these two criteria were newly applied in defining group B, rates of unfavorable disease in group A and B was 15.6% and 14.7%, respectively (p = 0.886).

Conclusion

Overall rate of pathologically aggressive PCa harbored by potential candidates for AS may not be increased significantly with expansion of criteria to biopsy GS 3+4 under most contemporary AS protocols. PSAD and tumor length of biopsy GS 3+4 core may be useful predictors of more aggressive disease among potential candidates for AS with biopsy GS 3+4.     

Evaluation of Relapse-Free Survival in T3N0 Colon Cancer: The Role of Chemotherapy,a Multicentric Retrospective Analysis

Background

Adjuvant chemotherapy (AC) in Stage II Colon Cancer (CC) is still under debate. Choice should be based on patients and disease characteristics. According to guidelines AC should be considered in high-risk T3N0 patients. No data are available for better option in low-risk patients. The aim of the study is to retrospectively evaluate relapse-free survival (RFS) and disease-free survival (DFS) according to treatment received in T3N0 CC.

Methods

RFS and DFS are evaluated with Kaplan-Meier method. Multivariate Cox proportional hazard model was developed using stepwise regression, enter limit and remove limit were p = 0.10 and p = 0.15, respectively.

Results

834 patients with T3N0 CC were recruited. Median age was 69 (29–93), M/F 463/371, 335 low-risk patients (40.2%), 387 high-risk (46.4%), 112 unknown (13.4%); 127 (15.2%) patients showed symptoms at diagnosis. Median sampled lymph nodes were 15 (1–76); 353 (42.3%) patients were treated with AC. Median follow up was 5 years (range 3–24). The 5-years RFS was 78.4% and the 5-years DFS was 76.7%. At multivariate analysis symptoms, lymph nodes, and adjuvant chemotherapy were prognostic factors for RFS. AC is prognostic factor for all endpoints.In low-risk group 5-years RFS was 87.3% in treated patients and 74.7% in non-treated patients (p 0.03); in high-risk group was respectively 82.7% and 71.4% (p 0.005).

Conclusions

Data confirmed the role of known prognostic factors and suggest the relevance of adjuvant chemotherapy also in low-risk stage II T3N0 CC patients. However, the highest risk in low-risk subgroup should be identified to be submitted to AC.     

Glasgow Coma Scale and Outcomes after Structural Traumatic Head Injury in Early Childhood

Objective

To assess the association of the Glasgow Coma Scale (GCS) with radiological evidence of head injury (the Abbreviated Injury Scale for the head region, AIS-HR) in young children hospitalized with traumatic head injury (THI), and the predictive value of GCS and AIS-HR scores for long-term impairment.

Methods

Our study involved a 10-year retrospective review of a database encompassing all patients admitted to Starship Children’s Hospital (Auckland, New Zealand, 2000–2010) with THI.

Results

We studied 619 children aged <5 years at the time of THI, with long-term outcome data available for 161 subjects. Both GCS and AIS-HR scores were predictive of length of intensive care unit and hospital stay (all p<0.001). GCS was correlated with AIS-HR (ρ=-0.46; p<0.001), although mild GCS scores (13–15) commonly under-estimated the severity of radiological injury: 42% of children with mild GCS scores had serious–critical THI (AIS-HR 3–5). Increasingly severe GCS or AIS-HR scores were both associated with a greater likelihood of long-term impairment (neurological disability, residual problems, and educational support). However, long-term impairment was also relatively common in children with mild GCS scores paired with structural THI more severe than a simple linear skull fracture.

Conclusion

Severe GCS scores will identify most cases of severe radiological injury in early childhood, and are good predictors of poor long-term outcome. However, young children admitted to hospital with structural THI and mild GCS scores have an appreciable risk of long-term disability, and also warrant long-term follow-up.     

Serum Levels of 25-Hydroxyvitamin D and Functional Outcome among Postmenopausal Women with Hip Fracture

Objective

The main objective of the current study was to assess the distribution and its prognostic value of serum 25-hydroxyvitamin D (25[OH] D) levels assessed at admission in Chinese postmenopausal women with hip fracture.

Methods

From January 1, 2012 to December 31, 2013, all postmenopausal women with first-ever hip fracture were recruited to participate in the study. Serum 25[OH] D levels were measured at admission. The functional evaluation at the time of discharge was performed by the Barthel Index (BI). The prognostic value of 25[OH] D to predict the functional outcome within discharge was analyzed by logistic regression analysis, after adjusting for the possible confounders.

Results

In our study, 261 patients were included and assessed. In the 76 patients with an unfavorable functional outcome, serum 25(OH) D levels were lower compared with those in patients with a favorable outcome [11.8(IQR, 9.9–16.1)ng/ml; 16.8(IQR, 13.6–21.4)ng/ml, respectively; P<0.0001]. In multivariate analysis, there was an increased risk of unfavorable outcome associated with serum 25(OH) D levels ≤ 20ng/ml (OR 5.24, 95%CI: 3.11–8.15; P<0.0001) after adjusting for possible confounders.

Conclusions

Our data support an association between serum 25[OH] D levels and prognosis in Chinese postmenopausal women with hip fracture.     

A Genetic Variant rs1801274 in FCGR2A as a Potential Risk Marker for Kawasaki Disease: A Case-Control Study and Meta-Analysis

Objectives

Recent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene FCGR2A, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.

Methods

A case-control study was conducted in a Chinese Han population including 428 KD patients and 493 controls to examine the association between rs1801274 and KD susceptibility. A meta-analysis was performed in combination with the relevant published studies to further clarify such an association.

Results

Our case-control study found that rs1801274 was significantly associated with increased risk of KD in the Chinese Han population, with an odds ratio (OR) of 1.58 (95% CI = 0.96–2.62) for the GA genotype and 1.93 (95% CI = 1.16–3.19) for the AA genotype compared with the GG genotype. The result of meta-analysis further demonstrated that the A allele of rs1801274 was significantly correlated with KD risk under the allelic model (OR = 1.35, 95% CI = 1.27–1.44) without heterogeneity by fixed-effects model analysis (Q = 17.30, p = 0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis.

Conclusion

These results further confirm that rs1801274 in the FCGR2A gene is significantly associated with increased risk of KD.     

Association between Seminal Vesicle Invasion and Prostate Cancer Detection Location after Transrectal Systemic Biopsy among Men Who Underwent Radical Prostatectomy

Background

Our hypothesis is that the location of the seminal vesicles near the base of the prostate, the more positive cores are detected in the base, the greater the risk of seminal vesicle invasion. Therefore we investigate the clinical outcomes of base dominant prostate cancer (BDPC) in transrectal ultrasound (TRUS) -guided biopsies compared with anteromiddle dominant prostate cancer (AMPC).

Methods

From November 2003 to June 2014, a total of 990 intermediate and high risk prostate cancer (PCa) patients who underwent radical prostatectomy (RP) were enrolled and stratified into two groups according to proportion of positive cores–BDPC group had ≥ 33.3% ratio of positive cores from the prostate base among all positive cores and AMPC group < 33.3% in systemic biopsy. Between two groups, we compared the rate of pathologic outcomes and biochemical recurrence (BCR). We performed multivariate logistic regression model to confirm the significance of BDPC to seminal vesicle invasion (SVI) and Cox proportional hazard analysis to BCR.

Results

Among these 990 PCa patients, the 487 patients in BDPC group had more advanced clinical stage (p<0.001), a higher biopsy GS (p = 0.002), and a higher rate of extracapsular extension (ECE), SVI and BCR (all p<0.001) than AMPC group. The patients in BDPC group had poor BCR free survival rate via Kaplan-meier analysis (p<0.001). The ratio of the base positive cores was a significant predictor to SVI in multivariate analysis (p < 0.001) and significant predictor of BCR in multivariate Cox proportional analysis (hazard ratio: 1.466, p = 0.004).

Conclusions

BDPC in TRUS-guided prostate biopsies was significantly associated with SVI and BCR after adjusting for other clinical factors. Therefore, BDPC should be considered to be a more aggressive tumor despite an otherwise similar cancer profile.     

Is Bladder Tumor Location Associated with Prostate Cancer Detection after Intravesical Bacillus Calmette-Guérin Instillation?

Objectives

The aim of this study was to evaluate the effect of bladder tumor (BT) location on prostate cancer (PCa) detection in patients with elevated PSA levels after intravesical BCG instillation.

Methods

Between February 2004 and January 2013 prostate biopsies were performed in 59 non-muscle invasive bladder cancer (NMIBC) patients whose PSA level were elevated (≥3 ng/ml) after a 6 week course of intravesical BCG (Oncotice, 12.5 mg in 50 ml normal saline). Differences in PCa detection according to the BT location [bladder neck and/or trigone (Group 1, n = 22) vs. other locations (Group 2, n = 37)] were evaluated. The Fisher''s exact test and the Mann-Whitney U test were used to evaluate the association between categorical and continuous variables, respectively.

Results

A total of 14 patients (23.7%) were diagnosed with PCa. The mean ± standard deviation (SD) PSA before intravesical BCG instillation and prostate biopsy were 1.36±1.04 ng/ml in Group 1 and 1.09±1.12 ng/ml in Group 2 (P = 0.633), and 6.05±3.57 ng/ml in Group 1 and 5.13±3.88 ng/ml in Group 2 (P = 0.378), respectively. Interestingly, whereas PCa was detected upon biopsy in only one patient in Group 1 (4.5%), 13 cases were detected in Group 2 (35.1%) (P = 0.009).

Conclusions

PCa detection after intravesical BCG was highly associated with BT location. Prostate biopsy should therefore be considered when PSA level is elevated after BCG instillation and his BT is located far from the bladder neck.     

Risk of Narcolepsy Associated with Inactivated Adjuvanted (AS03) A/H1N1 (2009) Pandemic Influenza Vaccine in Quebec

Context

An association between an adjuvanted (AS03) A/H1N1 pandemic vaccine and narcolepsy has been reported in Europe.

Objective

To assess narcolepsy risk following administration of a similar vaccine in Quebec.

Design

Retrospective population-based study.

Setting

Neurologists and lung specialists in the province were invited to report narcolepsy cases to a single reference centre.

Population

Patients were interviewed by two sleep experts and standard diagnostic tests were performed. Immunization status was verified in the provincial pandemic influenza vaccination registry.

Main Outcome Measures

Confirmed narcolepsy with or without cataplexy with onset of excessive daytime sleepiness between January 1^st, 2009, and December 31^st, 2010. Relative risks (RRs) were calculated using a Poisson model in a cohort analysis, by a self-controlled case series (SCCS) and a case-control method.

Results

A total of 24 cases were included and overall incidence rate was 1.5 per million person-years. A cluster of 7 cases was observed among vaccinated persons in the winter 2009–2010. In the primary cohort analysis, 16-week post-vaccination RR was 4.32 (95% CI: 1.50–11.12). RR was 2.07 (0.70–6.17) in the SCCS, and 1.48 (0.37–7.03) using the case-control method. Estimates were lower when observation was restricted to the period of pandemic influenza circulation, and tended to be higher in persons <20 years old and for cataplexy cases.

Conclusions

Results are compatible with an excess risk of approximately one case per million vaccine doses, mainly in persons less than 20 years of age. However, a confounding effect of the influenza infection cannot be ruled out.     

Relationships between the Osteocalcin Gene Polymorphisms,Serum Osteocalcin Levels,and Hepatitis B Virus-Related Hepatocellular Carcinoma in a Chinese Population

Background

Available evidence has demonstrated that osteocalcin may play a role in pathogenesis of cancer, and mutation of the osteocalcin gene may be involved in the cancer development. The aim of this study is to determine whether osteocalcin gene polymorphisms are associated with hepatitis B virus (HBV) related hepatocellular carcinoma (HCC) among Chinese population.

Methods

A total of 515 subjects were divided into four groups: 129 patients with chronic hepatitis B (CHB), 62 patients with HBV-related liver cirrhosis (LC), 154 patients with HBV-related HCC, and 170 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect osteocalcin gene rs1800247 and rs1543297 polymorphisms.

Results

Compared with healthy controls, the rs1800247 HH and Hh genotypes were associated with a significantly increased susceptibility to HCC (HH versus hh: OR = 6.828, 95% CI 2.620–17.795, P <0.001; Hh versus hh: OR = 6.306, 95% CI 3.480–11.423, P <0.001, respectively). Similarly, the subjects bearing the H allele of rs1800247 had more than a 2.4-fold increased risk for development of HCC (OR = 2.484, 95% CI 1.747–3.532, P <0.001) compared with those bearing the h allele. In addition, we found significant decreased serum osteocalcin levels in HBV-related HCC patients (11.73±8.18 ng/mL) compared with healthy controls (15.3±6.06 ng/mL). Furthermore, the serum osteocalcin levels were significantly lower in HCC patients than healthy controls among the individuals with heterozygous Hh genotype (P = 0.003) and CT genotype (P <0.001). In contrast, there were no significant differences in the genotype and allele of rs1543297 polymorphisms between the groups of patients and healthy controls.

Conclusions

These findings for the first time suggest that genetic variant in osteocalcin gene rs1800247 polymorphisms may be a risk factor for HBV-related HCC. We also find an inverse association of serum osteocalcin levels with HCC.     

Insulin Therapy and Risk of Prostate Cancer: a Systematic Review and Meta-Analysis of Observational Studies

Background

Previous observational studies have shown that insulin therapy may modify the risk of prostate cancer (PCa). However, these studies yielded controversial results. Thus, we performed this meta-analysis to determine whether insulin use was associated with PCa risk in patients with diabetes mellitus (DM).

Method

A literature search was carried out in PubMed, EMBASE, and Cochrane Library Central database between January 1966 and January 2013. Fixed-effect and random-effect models were used to estimate pooled relative risks (RR) and corresponding 95% confidence intervals (CIs). Subgroup analyses and sensitivity analyses were also performed.

Result

A total of 11 (10 cohorts, and one case–control) studies published between 2007 and 2013 were included in the meta-analysis, representing data for 205,523 male subjects and 7,053 PCa cases. There were five studies investigating the influence of insulin and other glucose-lowering agents on the risk of PCa , and six studies investigating the influence of glargine and non-glargine insulin. Insulin use was not associated with PCa risk when compared with other glucose-lowering agents (RR=0.89, 95% CI, 0.72-1.09). Use of insulin glargine did not contribute to susceptibility to PCa as compared with use of non-glargine insulin (RR=1.26, 95% CI, 0.86-1.84). Sensitivity analysis confirmed the stability of present results, since no individual study affected the pooled result significantly.

Conclusions

Our results suggest that, there may be no significant association between insulin use and risk of PCa as compared with other glucose-lowering agents in patients with DM, and there was no substantial evidence for increase risk of PCa among insulin glargine users as compared to non-glargine insulin users. Further studies are warranted to validate these conclusions.