Impact of Risk Factors on Different Interval Cancer Subtypes in a Population-Based Breast Cancer Screening Programme

Background

Interval cancers are primary breast cancers diagnosed in women after a negative screening test and before the next screening invitation. Our aim was to evaluate risk factors for interval cancer and their subtypes and to compare the risk factors identified with those associated with incident screen-detected cancers.

Methods

We analyzed data from 645,764 women participating in the Spanish breast cancer screening program from 2000–2006 and followed-up until 2009. A total of 5,309 screen-detected and 1,653 interval cancers were diagnosed. Among the latter, 1,012 could be classified on the basis of findings in screening and diagnostic mammograms, consisting of 489 true interval cancers (48.2%), 235 false-negatives (23.2%), 172 minimal-signs (17.2%) and 114 occult tumors (11.3%). Information on the screening protocol and women''s characteristics were obtained from the screening program registry. Cause-specific Cox regression models were used to estimate the hazard ratios (HR) of risks factors for interval cancer and incident screen-detected cancer. A multinomial regression model, using screen-detected tumors as a reference group, was used to assess the effect of breast density and other factors on the occurrence of interval cancer subtypes.

Results

A previous false-positive was the main risk factor for interval cancer (HR = 2.71, 95%CI: 2.28–3.23); this risk was higher for false-negatives (HR = 8.79, 95%CI: 6.24–12.40) than for true interval cancer (HR = 2.26, 95%CI: 1.59–3.21). A family history of breast cancer was associated with true intervals (HR = 2.11, 95%CI: 1.60–2.78), previous benign biopsy with a false-negatives (HR = 1.83, 95%CI: 1.23–2.71). High breast density was mainly associated with occult tumors (RRR = 4.92, 95%CI: 2.58–9.38), followed by true intervals (RRR = 1.67, 95%CI: 1.18–2.36) and false-negatives (RRR = 1.58, 95%CI: 1.00–2.49).

Conclusion

The role of women''s characteristics differs among interval cancer subtypes. This information could be useful to improve effectiveness of breast cancer screening programmes and to better classify subgroups of women with different risks of developing cancer.     

The Association of Pioglitazone and Urinary Tract Disease in Type 2 Diabetic Taiwanese: Bladder Cancer and Chronic Kidney Disease

Objective

Although studies have shown an association between pioglitazone and bladder cancer, the associated factors have not been identified. The aim of this study was to investigate the factors that may link pioglitazone to bladder cancer.

Materials and Methods

In total, 34,970 study subjects were identified from the National Health Insurance Research Database in 2003 with follow-up from 2005 to 2009. The demographic characteristics of patients who had used and had never used pioglitazone, including age, sex, diabetes duration, urinary tract disease, nephropathy, bladder cancer, and cumulative dose and duration of pioglitazone therapy, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of pioglitazone on bladder cancer and newly developed chronic kidney disease.

Results

Among 3,497 ever users and 31,473 never users of pioglitazone, the respective incident cases of bladder cancer were 12 (0.4%) and 72 (0.2%), and for newly developed chronic kidney disease 245 (8.1%) and 663 (2.3%), respectively. Ever use of pioglitazone [1.59(1.32–1.91)], cumulative dose of pioglitazone <10,500 mg [1.69 (1.37–2.01)] and >10,500 mg [1.34 (1.04–1.73)], and duration of therapy <12 months [1.68 (1.36–2.08)] and >12 months [1.39 (1.09–1.76)] were associated with the development of chronic kidney disease.

Conclusions

There was no association of pioglitazone use with bladder cancer development, however, there was an association with an increased risk of newly developed chronic kidney disease.     

Association of Sick Sinus Syndrome with Incident Cardiovascular Disease and Mortality: The Atherosclerosis Risk in Communities Study and Cardiovascular Health Study

Background

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population.

Methods

We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes.

Results

During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14–1.70), coronary heart disease (HR 1.72, 95%CI 1.11–2.66), heart failure (HR 2.87, 95%CI 2.17–3.80), stroke (HR 1.56, 95%CI 0.99–2.46), AF (HR 5.75, 95%CI 4.43–7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9–67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51–2.66), AF (HR 4.25, 95%CI 3.28–5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8–32.1).

Conclusion

Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.     

Type 2 Diabetes Mellitus and Kidney Cancer Risk: A Retrospective Cohort Analysis of the National Health Insurance

Purpose

To evaluate the association between incidence of any kidney cancer and type 2 diabetes mellitus.

Methods

A random sample of 1,000,000 subjects covered by the National Health Insurance was recruited. A total of 998728 people (115655 diabetes and 883073 non-diabetes) without kidney cancer at recruitment were followed from 2003 to 2005. The cumulative incidence of kidney cancer from 2003 to 2005 in diabetic patients and non-diabetic people in all ages and in age <40, 40–64, 65–74 and ≥75 years were calculated in the diabetic patients and the non-diabetic people, respectively. Logistic regression was used to estimate the odds ratios comparing diabetic patients to non-diabetic people in the respective age groups. Multivariable-adjusted odds ratios for kidney cancer with regards to diabetes status and diabetes duration (as a continuous variable or categorized into subgroups of non-diabetes, diabetes duration <1 year, 1–2.9 years, 3–4.9 years and ≥5 years) were estimated after multivariable adjustment. The multivariable-adjusted odds ratios for all baseline variables were also estimated for diabetic patients and non-diabetic people, respectively.

Results

The 3-year cumulative incidence of kidney cancer in the diabetic patients and the non-diabetic people was 166.9 and 33.1 per 100,000 person-years, respectively. The incidence increased with regards to increasing age in both the diabetic patients and the non-diabetic people, but a higher risk of kidney cancer for the diabetic patients compared to the non-diabetic people was consistently observed in different age groups. After multivariable adjustment, the odds ratio for diabetic patients versus non-diabetic people was 1.7 (95% confidence interval: 1.3–2.1, P<0.01). While compared to the non-diabetic people, the odds ratio (95% confidence interval) for diabetes duration <1, 1–2.9 years, 3–4.9 years and ≥5 years was 1.5 (0.8–2.7), 1.6 (1.0–2.4), 1.6 (1.1–2.4) and 1.7 (1.3–2.3), respectively (P-trend <0.01). Analyses conducted in the diabetic patients and the non-diabetic people, respectively, consistently showed age, nephropathy and end-stage renal disease as significant risk factors of kidney cancer. Additionally, living in metropolitan Taipei region might also be associated with a higher risk of kidney cancer in the non-diabetic people, indicating a potential link between kidney cancer and some factors related to urbanization.

Conclusions

Patients with type 2 diabetes mellitus have a significantly higher risk of kidney cancer.     

Incidence of Cancer in ANCA-Associated Vasculitis: A Meta-Analysis of Observational Studies

ObjectiveThe purpose of this paper is to examine cancer incidence in patients with ANCA-associated vasculitis (AASV) derived from population-based cohort studies by means of meta-analysis.MethodsRelevant electronic databases were searched for studies characterizing the associated risk of overall malignancy in patients with AASV. Standardized incidence rates (SIRs) with 95% confidence intervals (CIs) were used to evaluate the strength of association. We tested for publication bias and heterogeneity and stratified for site-specific cancers.ResultsSix studies (n = 2,578) were eventually identified, of which six provided the SIR for overall malignancy, five reported the SIR for non-melanoma skin cancer (NMSC), four for leukemia, five for bladder cancer, three for lymphoma, three for liver cancer, four for lung cancer, three for kidney cancer, four for prostate cancer, four for colon cancer and four for breast cancer. Overall, the pooled SIR of cancer in AASV patients was 1.74 (95%CI = 1.37–2.21), with moderate heterogeneity among these studies (I² = 65.8%, P = 0.012). In sub-analyses for site-specific cancers, NMSC, leukemia and bladder cancer were more frequently observed in patients with AASV with SIR of 5.18 (95%CI = 3.47–7.73), 4.89 (95%CI = 2.93–8.16) and 3.84 (95%CI = 2.72–5.42) respectively. There was no significant increase in the risk of kidney cancer (SIR = 2.12, 95%CI = 0.66–6.85), prostate cancer (SIR = 1.45, 95%CI = 0.87–2.42), colon cancer (SIR = 1.26, 95%CI = 0.70–2.27), and breast cancer (SIR = 0.95, 95%CI = 0.50–1.79). Among these site-specific cancers, only NMSC showed moderate heterogeneity (I² = 55.8%, P = 0.06). No publication bias was found by using the Begg’s test and Egger''s test.ConclusionsThis meta-analysis shows that AASV patients treatment with cyclophosphamide (CYC) are at increased risk of late-occurring malignancies, particularly of the NMSC, leukemia and bladder cancer. However, there is no significant association between AASV and kidney cancer, prostate cancer, colon cancer and breast cancer. These findings emphasize monitoring and preventative management in AASV patients after cessation of CYC therapy is momentous.     

Randomization to Screening for Prostate,Lung, Colorectal and Ovarian Cancers and Thyroid Cancer Incidence in Two Large Cancer Screening Trials

Background

Thyroid cancer incidence has increased significantly over the past three decades due, in part, to incidental detection. We examined the association between randomization to screening for lung, prostate, colorectal and/or ovarian cancers and thyroid cancer incidence in two large prospective randomized screening trials.

Methods

We assessed the association between randomization to low-dose helical CT scan versus chest x-ray for lung cancer screening and risk of thyroid cancer in the National Lung Screening Trial (NLST). In the Prostate Lung Colorectal and Ovarian Cancer Screening Trial (PLCO), we assessed the association between randomization to regular screening for said cancers versus usual medical care and thyroid cancer risk. Over a median 6 and 11 years of follow-up in NLST and PLCO, respectively, we identified 60 incident and 234 incident thyroid cancer cases. Cox proportional hazards regression was used to calculate the cause specific hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer.

Results

In NLST, randomization to lung CT scan was associated with a non-significant increase in thyroid cancer risk (HR  = 1.61; 95% CI: 0.96–2.71). This association was stronger during the first 3 years of follow-up, during which participants were actively screened (HR  = 2.19; 95% CI: 1.07–4.47), but not subsequently (HR  = 1.08; 95% CI: 0.49–2.37). In PLCO, randomization to cancer screening compared with usual care was associated with a significant decrease in thyroid cancer risk for men (HR  = 0.61; 95% CI: 0.49–0.95) but not women (HR  = 0.91; 95% CI: 0.66–1.26). Similar results were observed when restricting to papillary thyroid cancer in both NLST and PLCO.

Conclusion

Our study suggests that certain medical encounters, such as those using low-dose helical CT scan for lung cancer screening, may increase the detection of incidental thyroid cancer.     

Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients

Background

There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients.

Methods

We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles.

Results

The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377–3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147–4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178–3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167–6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005–2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171–2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761–3.250, P = 0.222; HR = 1.432, 95%CI: 0.108–19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211–2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547–3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921–4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685–5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620–3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625–3.568, P<0.001).

Conclusions

The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.     

Risk of Post-Discharge Venous Thromboembolism and Associated Mortality in General Surgery: A Population-Based Cohort Study Using Linked Hospital and Primary Care Data in England

Background

Trends towards day case surgery and enhanced recovery mean that postoperative venous thromboembolism (VTE) may increasingly arise after hospital discharge. However, hospital data alone are unable to capture adverse events that occur outside of the hospital setting. The National Institute for Health and Care Excellence has suggested the use of primary care data to quantify hospital care-related VTE. Data in surgical patients using these resources is lacking. The aim of this study was to measure VTE risk and associated mortality in general surgery using linked primary care and hospital databases, to improve our understanding of harm from VTE that arises beyond hospital stay.

Methods

This was a longitudinal cohort study using nationally linked primary care (Clinical Practice Research Datalink, CPRD), hospital administrative (Hospital Episodes Statistics, HES), population statistics (Office of National Statistics, ONS) and National Cancer Intelligence Network databases. Routinely collected information was used to quantify 90-day in-hospital VTE, 90-day post-discharge VTE and 90-day mortality in adults undergoing one of twelve general surgical procedures between 1st April 1997 and 31st March 2012. The earliest postoperative recording of deep vein thrombosis or pulmonary embolism in CPRD, HES and ONS was counted in each patient. Covariates from multiple datasets were combined to derive detailed prediction models for VTE and mortality. Limitation included the capture of VTE presenting to healthcare only and the lack of information on adherence to pharmacological thromboprophylaxis as there was no data linkage to hospital pharmacy records.

Results

There were 981 VTE events captured within 90 days of surgery in 168005 procedures (23.7/1000 patient-years). Overall, primary care data increased the detection of postoperative VTE by a factor of 1.38 (981/710) when compared with using HES and ONS only. Total VTE rates ranged between 3.2/1000 patient-years in haemorrhoidectomy to 118.3/1000 patient-years in esophagogastric resection. Predictors of VTE included emergency surgery (OR = 1.91 95%CI 1.60–2.28, p<0.001), age (OR = 1.02 95%CI 1.02–1.03, p<0.001), body mass index (OR = 1.03 95%CI 1.01–1.04, p<0.001), previous VTE (OR = 8.07 95%CI 6.61–9.83, p<0.001), length of stay (OR = 1.00 95%CI 1.00–1.00, p = 0.007) and cancer stages II (OR = 1.38 95%CI 1.03–1.87, p = 0.033), III (OR = 1.50 95%CI 1.11–2.01, p = 0.008) and IV (OR = 1.63 95%CI 1.03–2.59, p = 0.038). Major organ resections had the greatest odds of VTE when adjusted for other risk factors including length of hospital stay. Post-discharge VTE accounted for 64.8% (636/981) of all recorded VTE. In-hospital VTE (165.4/1000 patient-years) was recorded more frequently than post-discharge VTE (16.2/1000 patient-years). Both in-hospital (OR = 2.07 95%CI 1.51–2.85, p<0.001) and post-discharge (OR = 4.03 95%CI 2.95–5.51, p<0.001) VTE independently predicted 90-day mortality. In patients who died and VTE was recorded on HES or CPRD (n = 56), VTE was one of the causes of death in 37.5% (21/56) of cases.

Conclusions

A large proportion of postoperative VTE was detected in primary care. Evaluation of linked databases was a useful way of measuring postoperative VTE at population level. These resources identified a significant association between post-discharge VTE and mortality in general surgery.     

Overexpression of MMP Family Members Functions as Prognostic Biomarker for Breast Cancer Patients: A Systematic Review and Meta-Analysis

Background

Matrix metalloproteinases (MMPs) are regarded to be relevant to the prognosis of breast cancer. Numerous studies have confirmed the association between MMPs and tumor growth, invasion and metastasis in breast cancer. However, their prognostic values for survival in patients with breast cancer remain controversial. Hence, a meta-analysis was performed to clarify a more accurate estimation of the role of MMPs on prognosis of breast cancer patients.

Method

A systemic electronic search was conducted in PubMed, Embase and Web of science databases to identify eligible studies, which were associated with the relationship between MMPs and prognosis of breast cancer. The correlation in random-effect model was evaluated by using the hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

A total of 28 studies covering 4944 patients were included for meta-analysis. A summary hazard ratio (HR) of all studies was calculated, as well as the sub-group HRs. The combined HRs calculated by either univariate or multivariate analysis both suggested that overexpression of MMPs had an unfavorable impact on overall survival (OS) (HR = 1.694, 95%CI: 1.347–2.129, P < 0.001; HR = 1.611, 95%CI: 1.419–1.830, P < 0.001, respectively). And the univariate analysis showed that patients with overexpression of MMPs had worse relapse-free survival (RFS) (HR = 1.969, 95%CI: 1.460–2.655, P < 0.001) in all eligible studies. In the sub-group analyses, HRs of MMP-9 positivity with poor OS were 1.794 (95%CI: 1.330–2.420, P < 0.001) and 1.709 (95%CI: 1.157–2.526, P = 0.007) which were separately evaluated by univariate and multivariate analysis. A small number of articles demonstrated that MMP-2 overexpression was not related with shorter OS (HR = 1.400, 95%CI: 0.610–3.029, P = 0.427). Four studies included in the OS analysis of MMPs expression in serum suggested that positive expression of serum MMPs may be an unfavorable factor (HR = 1.630, 95%CI: 1.065–2.494) for breast cancer patients. No publication bias was observed in the current meta-analysis.

Conclusions

Our findings suggested that MMPs overexpression (especially MMP-9, MMP-2, MMPs overexpression in serum) might indicate a higher risk of poor prognosis in breast cancer. Larger prospective studies are further needed to estimate the prognostic values of MMPs overexpression.     

The Effect of MUC1 rs4072037 Functional Polymorphism on Cancer Susceptibility: Evidence from Published Studies

Genome-wide association studies have identified a susceptibility variation MUC1 rs4072037 for gastric cancer in Chinese population. Subsequent case-control studies have reported this association in other populations. However, the results remain controversial and ambiguous. The aim of this study is to provide a precise quantification for the association between MUC1 rs4072037 variation and the risk of cancer. We performed pooled analysis of 10 case-control designed studies including 4,220 cases and 6,384 controls. Odds ratios (OR) and 95% confidence interval (95%CI) were calculated to assess strength of association in overall studies and in subgroup analysis stratified by ethnicity and cancer types. All statistical analyses were performed by Manager 5.0 and Stata 12.0 software. Overall, the MUC1 rs4072037 polymorphism was associated with risk of cancer in all genetic models (G vs A: OR = 0.71, 95%CI: 0.63–0.80, p<0.01; GA vs AA: OR = 0.61, 95%CI:0.55–0.67, p<0.01; GG vs AA: OR = 0.58, 95%CI: 0.47–0.71, p<0.01; AG+AA vs GG: OR = 0.60, 95%CI: 0.55–0.60, p<0.01; GG vs AG+AA: OR = 0.70, 95%CI: 0.58–0.85, p<0.01). Further, subgroup analysis based on ethnicity suggested MUC1 rs4072037 polymorphism had a subtly reduced cancer risk among Asian population, and stratified analysis by cancer types showed significantly decreased risk of gastric cancer in all genetic models. In conclusion, MUC1 rs4072037 polymorphism may be used as potential biomarker for cancer susceptibility particularly for gastric cancer and for Asian population.     

Five-Year Incidence of Chronic Kidney Disease (Stage 3-5) and Associated Risk Factors in a Spanish Cohort: The MADIABETES Study

Objective

To evaluate the incidence rate of Chronic Kidney Disease (CKD) stage 3-5 (persistent decreased kidney function under 60 mL/min per 1.73 m²) among patients with type 2 diabetes over five years, to identify the risk factors associated with CKD, and develop a risk table to predict five-year CKD stage 3-5 risk stratification for clinical use.

Design

The MADIABETES Study is a prospective cohort study of 3,443 outpatients with type 2 diabetes mellitus, sampled from 56 primary health care centers (131 general practitioners) in Madrid (Spain).

Results

The cumulative incidence of CKD stage 3-5 at five-years was 10.23% (95% CI = 9.12–11.44) and the incidence density was 2.07 (95% CI = 1.83–2.33) cases per 1,000 patient-months or 2.48 (95% CI = 2.19–2.79) cases per 100 patient-years. The highest hazard ratio (HR) for developing CKD stage 3-5 was albuminuria ≥300 mg/g (HR = 4.57; 95% CI= 2.46-8.48). Furthermore, other variables with a high HR were age over 74 years (HR = 3.20; 95% CI = 2.13–4.81), a history of Hypertension (HR = 2.02; 95% CI = 1.42–2.89), Myocardial Infarction (HR= 1.72; 95% IC= 1.25–2.37), Dyslipidemia (HR = 1.68; 95% CI 1.30–2.17), duration of diabetes mellitus ≥ 10 years (HR = 1.46; 95% CI = 1.14-1.88) and Systolic Blood Pressure >149 mmHg (HR = 1.52; 95% CI = 1.02–2.24).

Conclusions

After a five-year follow-up, the cumulative incidence of CKD is concordant with rates described in Spain and other countries. Albuminuria ≥ 300 mg/g and age over 74 years were the risk factors more strongly associated with developing CKD (Stage 3-5). Blood Pressure, lipid and albuminuria control could reduce CKD incidence of CKD in patients with T2DM.     

Recipient-Related Risk Factors for Graft Failure and Death in Elderly Kidney Transplant Recipients

Background

Elderly patients with end-stage renal disease have become the fastest growing population of kidney transplant candidates in recent years. However, the risk factors associated with long-term outcomes in these patients remain unclear.

Methods

We retrospectively analyzed 166 recipients aged 60 years or older who underwent primary deceased kidney transplantation between 2002 and 2013 in our center. The main outcomes included 1-, 3- and 5-year patient survival as well as overall and death-censored graft survival. The independent risk factors affecting graft and patient survival were analyzed using Cox regression analysis.

Results

The 1-, 3-, 5-year death-censored graft survival rates were 93.6%, 89.4% and 83.6%, respectively. Based on the Cox multivariate analysis, panel reactive antibody (PRA)>5% [hazard ratio (HR) 4.295, 95% confidence interval (CI) 1.321–13.97], delayed graft function (HR 4.744, 95% CI 1.611–13.973) and acute rejection (HR 4.971, 95% CI 1.516–16.301) were independent risk factors for graft failure. The 1-, 3-, 5-year patient survival rates were 84.8%, 82.1% and 77.1%, respectively. Longer dialysis time (HR 1.011 for 1-month increase, 95% CI 1.002–1.020), graft loss (HR 3.501, 95% CI 1.559–7.865) and low-dose ganciclovir prophylaxis (1.5 g/d for 3 months) (HR 3.173, 95% CI 1.063–9.473) were risk factors associated with patient death.

Conclusions

The five-year results show an excellent graft and patient survival in elderly kidney transplant recipients aged ≥60 years. PRA>5%, delayed graft function, and acute rejection are risk factors for graft failure, while longer duration of dialysis, graft loss and low-dose ganciclovir prophylaxis are risk factors for mortality in elderly recipients. These factors represent potential targets for interventions aimed at improving graft and patient survival in elderly recipients.     

Associations between the Genetic Polymorphisms of Osteopontin Promoter and Susceptibility to Cancer in Chinese Population: A Meta-Analysis

Background and Aim

Several studies have been conducted to examine the associations between osteopontin (OPN) promoter gene SPP1 polymorphisms with human cancers in Chinese population, but the results remain inconsistent. The aim of this meta-analysis is to clarify the associations between SPP1 polymorphisms and cancer susceptibility.

Methods

All eligible case-control studies published up to March 2015 were identified by searching PubMed, Web of Science, Embase, and Cochrane Library without language restrictions. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated using fixed- or random-effect model.

Results

A total of 11 case-control studies were included; of those, there were eleven studies (3130 cases and 3828 controls) for -443T>C polymorphism, ten studies (3019 cases and 3615 controls) for -156G>GG polymorphism, eight studies (2258 cases and 2846 controls) for -66T>G polymorphism. Overall, no evidence indicated that the -443 T>C polymorphism was associated with cancer risk (OR = 0.93, 95%CI 0.62–1.38 for dominant model, OR = 1.06, 95%CI 0.73–1.55 for recessive model, OR = 0.88, 95%CI 0.62–1.26 for CT vs TT model, OR = 1.03, 95%CI 0.61–1.73 for CC vs TT model). While, a significantly increase risk was found for -156 G>GG polymorphism (OR = 1.22, 95%CI 1.10–1.35 for dominant model, OR = 1.25, 95%CI 1.10–1.41 for recessive model, OR = 1.18, 95%CI 1.06–1.32 for GGG vs GG model, OR = 1.35, 95%CI 1.09–1.68 for GGGG vs GG model). For -66T>G polymorphism, we found a decrease risk of cancer (OR = 0.84, 95% CI 0.71–0.98 for dominant model), but this result changed (OR = 0.93, 95% CI 0.77–1.12 for dominant model) when we excluded a study.

Conclusion

This meta-analysis suggests that in Chinese population the -156G>GG polymorphism of SPP1 might be a risk factor for human cancers, while -443T>C mutation is not associated with cancer risk. For -66T>G polymorphism, it may be a protective factor for human cancers.     

Alcohol Consumption,One-Carbon Metabolites,Liver Cancer and Liver Disease Mortality

Background

Excess alcohol consumption adversely affects one-carbon metabolism and increases the risk of liver disease and liver cancer. Conversely, higher folate levels have been inversely associated with liver damage. The current study investigated the effects of alcohol and one-carbon metabolite intake on liver cancer incidence and liver disease mortality within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study.

Methods

Cox proportional hazards modeling was used to calculate hazard ratios and 95% confidence intervals (CIs) in a population of 27,086 Finnish males with 194 incident liver cancers and 213 liver disease deaths. In a nested case-control subset (95 liver cancers, 103 controls), logistic regression was used to calculate odds ratios and 95% CIs for serum one-carbon metabolites in relation to liver cancer risk.

Results

Daily alcohol consumption of more than 20.44 g was associated with an increased risk of both liver cancer incidence (Hazard Ratio (HR) 1.52, 95%CI 1.06–2.18) and liver disease mortality (HR 6.68, 95%CI 4.16–10.71). These risks were unaffected by one-carbon metabolite intake. Similarly, in the case-control study, none of the serum one-carbon metabolites were associated with liver cancer.

Conclusions

The current study provided no convincing evidence for a protective association of one-carbon metabolite intake or serum level on the risk of liver cancer or liver disease mortality.     

Cancer risk in individuals with intellectual disability in Sweden: A population-based cohort study

BackgroundA knowledge gap exists about the risk of cancer in individuals with intellectual disability (ID). The primary aim of this study was to estimate the cancer risk among individuals with ID compared to individuals without ID.Methods and findingsWe conducted a population-based cohort study of all children live-born in Sweden between 1974 and 2013 and whose mothers were born in a Nordic country. All individuals were followed from birth until cancer diagnosis, emigration, death, or 31 December 2016 (up to age 43 years), whichever came first. Incident cancers were identified from the Swedish Cancer Register. We fitted Cox regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) as measures of cancer risk in relation to ID after adjusting for several potential confounders. We analyzed ID by severity, as well as idiopathic ID and syndromic ID separately. We performed a sibling comparison to investigate familial confounding. The study cohort included a total of 3,531,305 individuals, including 27,956 (0.8%) individuals diagnosed with ID. Compared with the reference group (individuals without ID and without a full sibling with ID), individuals with ID were in general more likely to be male. The median follow-up time was 8.9 and 23.0 years for individuals with ID and individuals without ID, respectively. A total of 188 cancer cases were identified among individuals with ID (incidence rate [IR], 62 per 1,000 person-years), and 24,960 among individuals in the reference group (IR, 31 per 1,000 person-years). A statistically significantly increased risk was observed for any cancer (HR 1.57, 95% CI 1.35–1.82; P < 0.001), as well as for several cancer types, including cancers of the esophagus (HR 28.4, 95% CI 6.2–130.6; P < 0.001), stomach (HR 6.1, 95% CI 1.5–24.9; P = 0.013), small intestine (HR 12.0, 95% CI 2.9–50.1; P < 0.001), colon (HR 2.0, 95% CI 1.0–4.1; P = 0.045), pancreas (HR 6.0, 95% CI 1.5–24.8; P = 0.013), uterus (HR 11.7, 95% CI 1.5–90.7; P = 0.019), kidney (HR 4.4, 95% CI 2.0–9.8; P < 0.001), central nervous system (HR 2.7, 95% CI 2.0–3.7; P < 0.001), and other or unspecified sites (HR 4.8, 95% CI 1.8–12.9; P = 0.002), as well as acute lymphoid leukemia (HR 2.4, 95% CI 1.3–4.4; P = 0.003) and acute myeloid leukemia (HR 3.0, 95% CI 1.4–6.4; P = 0.004). Cancer risk was not modified by ID severity or sex but was higher for syndromic ID. The sibling comparison showed little support for familial confounding. The main study limitations were the limited statistical power for the analyses of specific cancer types, and the potential for underestimation of the studied associations (e.g., due to potential underdetection or delayed diagnosis of cancer among individuals with ID).ConclusionsIn this study, we found that individuals with ID showed an increased risk of any cancer, as well as of several specific cancer types. These findings suggest that extended surveillance and early intervention for cancer among individuals with ID are warranted.

In a nationwide cohort study in Sweden, Qianwei Liu and co-workers report on cancer risk in people with intellectual disability.     

Dietary Total Antioxidant Capacity and Colorectal Cancer in the Italian EPIC Cohort

Background

Colorectal cancer is the third most common cancer worldwide. Diet has been hypothesized as involved in colorectal cancer etiology, but few studies on the influence of total dietary antioxidant intake on colorectal cancer risk have been performed.

Methods

We investigated the association between colorectal cancer risk and the total antioxidant capacity (TAC) of the diet, and also of intake of selected antioxidants, in 45,194 persons enrolled in 5 centers (Florence, Naples, Ragusa, Turin and Varese) of the European Prospective Investigation into Cancer and Nutrition (EPIC) Italy study. TAC was estimated by the Trolox equivalent antioxidant capacity (TEAC) assay. Hazard ratios (HRs) for developing colorectal cancer, and colon and rectal cancers separately, adjusted for confounders, were estimated for tertiles of TAC by Cox modeling, stratifying by center.

Results

Four hundred thirty-six colorectal cancers were diagnosed over a mean follow-up of 11.28 years. No significant association between dietary TAC and colorectal cancer incidence was found. However for the highest category of TAC compared to the lowest, risk of developing colon cancer was lower (HR: 0.63; 95% CI: 0.44–0.89, P trend: 0.008). By contrast, increasing TAC intake was associated with significantly increasing risks of rectal cancer (2nd tertile HR: 2.09; 95%CI: 1.19–3.66; 3rd tertile 2.48 95%CI: 1.32–4.66; P trend 0.007). Intakes of vitamin C, vitamin E, and ß-carotene were not significantly associated with colorectal cancer risk.

Conclusions

Further prospective studies are needed to confirm the contrasting effects of high total antioxidant intake on risk of colon and rectal cancers.     

LncRNA AWPPH as a prognostic predictor in human cancers in Chinese population: evidence from meta-analysis

Background: Long non-coding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is dysregulated in a variety of human cancers. However, the prognostic value of AWPPH in various cancers remains unclear.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR = 1.79, 95%CI: 1.44–2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR = 2.50, 95%CI: 1.94–3.22, P<0.001), bigger tumor size (OR = 2.64, 95%CI: 1.47–4.73, P=0.001), macro-vascular invasion (OR = 2.08, 95%CI: 1.04–4.16, P=0.04) and lymph node metastasis (OR = 2.68, 95%CI: 1.82–3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding.Conclusions: Up-regulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers among the Chinese population.     

Metformin Reduces Thyroid Cancer Risk in Taiwanese Patients with Type 2 Diabetes

Background

Whether metformin may affect thyroid cancer risk has not been studied. This study investigated the association between metformin use and thyroid cancer risk in Taiwanese patients with type 2 diabetes mellitus.

Methods

The reimbursement databases of all diabetic patients from 1996 to 2009 were retrieved from the National Health Insurance. An entry date was set at 1 January 2006 and 1,414,723 patients with type 2 diabetes were followed for thyroid cancer incidence until the end of 2009. Incidences for ever-users, never-users and subgroups of metformin exposure using tertile cutoffs for cumulative duration of therapy and cumulative dose were calculated and adjusted hazard ratios were estimated by Cox regression. Additional sensitivity analyses were conducted.

Results

There were 795,321 ever-users and 619,402 never-users, with respective numbers of incident thyroid cancer of 683 (0.09%) and 1,614 (0.26%), and respective incidence of 24.09 and 87.33 per 100,000 person-years. The overall fully adjusted hazard ratio (95% confidence interval) was 0.683 (0.598–0.780), and all categories of the dose-response parameters showed significantly lower risk with P-trends <0.0001. The protective effect of metformin on thyroid cancer incidence was also supported by sensitivity analyses, disregarding age (<50 or ≥50 years) and sex; and was not affected by excluding users of insulin, sulfonylurea, and insulin and/or sulfonylurea respectively, by previous diagnosis of other cancers or by potential detection examinations that might lead to differential diagnosis of thyroid cancer.

Conclusions

This study provides evidence for the first time that metformin use in patients with type 2 diabetes may reduce the risk of thyroid cancer.     

Lack of Association between Interleukin-10 Gene Polymorphisms and Graft Rejection Risk in Kidney Transplantation Recipients: A Meta-Analysis

Background

Interleukin-10 (IL-10) is an important immunomodulatory cytokine. Several studies focused the association between IL-10 promoter gene polymorphisms and graft rejection risk in kidney transplantation recipients. However, the results of these studies remain inconclusive. The aim of this study was to conduct a meta-analysis to further assess the associations.

Methods

The PubMed, Embase, and Ovid Medline databases were searched. Two independent authors extracted data, and the effects were estimated from an odds ratio (OR) with 95% confidence intervals (CIs). Subgroup and sensitivity analyses identified sources of heterogeneity.

Results

A total of 16 studies including 595 rejection patients and 1239 stable graft patients were included in order to study the IL-10 -1082 (rs1800896 G/A), -819 (rs1800871 C/T), -592 (rs1800872 C/A) and IL-10 (-1082,-819,-592) polymorphisms. The -1082 G/A polymorphism was not associated with an increased graft rejection risk (OR = 1.03; 95%CI, 0.85–1.25, P = 0.74 for GA+AA vs. GG model). Moreover, all of the -819 C/T (OR = 1.06, 95%CI, 0.79–1.42, P = 0.70 for TA+TT vs. CC model), -592 C/A (OR = 1.10, 95% CI, 0.85–1.42, P = 0.47 for AC+AA vs. CC model) and IL-10 (-1082,-819,-592) polymorphisms (OR = 1.00, 95%CI, 0.79–1.27, P = 0.98 for I+L vs. H model) did not increase the graft rejection risk. In addition, we also performed subgroup analysis by ethnic group (mainly in Europeans or Asians) and rejection type (acute or chronic). There was also lack of evidence of a significant association between the IL-10 gene polymorphism and graft rejection risk. The present meta-analysis indicated that the IL-10 gene polymorphism was not associated with graft rejection risk in kidney transplantation recipients.

Conclusion

This meta-analysis found evidence that the IL-10 polymorphism does not increase the risk of graft rejection in kidney transplantation recipients. Further chronic rejection and other ethnic population studies are needed to confirm our results.     

Salivary Immunoglobulin A Secretion Rate Is Negatively Associated with Cancer Mortality: The West of Scotland Twenty-07 Study

Immunoglobulins are essential for combating infectious disease although very high levels can indicate underlying pathology. The present study examined associations between secretory immunoglobulin A (sIgA) in saliva and mortality rates in the general population. Participants were 639 adults from the eldest cohort of the West of Scotland Twenty-07 Study aged 63 years at the time of saliva sampling in 1995. From unstimulated 2-minute saliva samples, saliva volume and S-IgA concentration were measured, and S-IgA secretion rate determined as their product. Mortality data were tracked for 19 years. Cox proportional hazard models were applied to compute hazard ratios (HR) for all-cause mortality from sIgA secretion rate. Associations were adjusted for gender, assay batch, household occupational group, smoking, medication usage, and self-reported health. There was a negative association between log sIgA secretion rate and all-cause mortality, HR = 0.81, 95%CI = 0.73–0.91, p < .001. Further analysis of specific causes of mortality revealed that the all-cause association was due to an underlying association with cancer mortality and in particular with cancers other than lung cancer. The HR for non-lung cancer was 0.68 (95%CI = 0.54 to 0.85) implying a 32% reduction in mortality risk per standard deviation rise in log sIgA secretion rate. Effects were stronger for men than women. For deaths from respiratory diseases, sIgA secretion had a non-linear relationship with mortality risk whereby only the very lowest levels of secretion were associated with elevated risk. SIgA concentration revealed a similar but weaker pattern of association. In the present study, higher secretion rates of sIgA were associated with a decreased risk of death from cancer, specifically non-lung cancer, as well as from respiratory disease. Thus, it appears that sIgA plays a protective role among older adults, and could serve as a marker of mortality risk, specifically cancer mortality.