Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to ...comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.
A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.
A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79,
<0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70,
<0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin's lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004,
=0.0035).
Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.
https://www.crd.york.ac.uk/PROSPERO/, CRD42021243635.
In the past decades, extremely serious road accidents with a death toll over ten in each have become a severe public health problem in China. This study investigates risk factors contributing to ...extremely serious road accidents, which will be crucial for accident prevention.
Collecting data from The Road Accident Statistical Annual Report openly issued by China's Traffic Management Bureau of the Public Security Ministry for the time period 2004-2015, we used the monthly case number of extreme serious road accidents as the dependent variable. We then selected ten risk factors as primary independent variables: professional driver, driving under influence (alcohol or drug), fatigue, vehicle type, overload, brake problem, weather, road classification, terrain, and region. The method of negative binominal regression was implemented to investigate the association between these risk factors and extremely serious road accidents.
A total of 346 extremely serious road accidents were included in our analysis. On a national scale, we found that professional driver incidence rate ratio (IRR): 1.10, 95% CI: 1.02-1.19, fatigue (IRR: 1.15, 95% CI: 1.03-1.29), large vehicle type (IRR: 1.11, 95% CI: 1.03-1.21), overload (IRR: 1.09, 95% CI: 1.03-1.16), and terrain (IRR: 1.09, 95% CI: 1.01-1.18) were significantly associated with extremely serious road accidents. Besides, separate analyses on western and non-western region indicated that both regions had shared risk factors as well as distinct factors.
Our study identifies professional driver, fatigue, large vehicle type, overload, and terrain as significant risk factors of extremely serious road accidents in China, and targeted and preventative measures could be taken based on our findings.
Trauma has been proposed as a risk factor for the development of psychiatric disorders. This study aimed to determine the causal role of trauma in six common psychiatric disorders.
We obtained ...summary-level data for genetic variants associated with trauma and the corresponding association with psychiatric disorders from previous genome-wide association studies. Two-sample Mendelian randomization analyzes were performed to estimate the causal association between trauma and psychiatric disorders, with inverse variance weighted used as the main method.
Genetically predisposed trauma was associated with an increased risk of psychiatric disorders odds ratio (OR) =1.24, 95%, confidence interval (CI), 1.09-1.40, anxiety disorder (OR = 1.30, 95% CI, 1.10-1.52) and schizophrenia (OR = 1.48, 95% CI, 1.18-1.84). However, the associations between trauma and sleep disorder (OR = 1.17, 95% CI, 1.01-1.35), as well as depression (OR = 1.09, 95% CI, 1.02-1.16) did not reach a Bonferroni corrected significance level. Besides, no association was observed between trauma and risk of bipolar disorder (OR = 1.21, 95% CI, 0.98-1.48) and eating disorder (OR = 1.28, 95% CI, 0.88-1.86).
Trauma might be causally associated with an increased risk of some common psychiatric disorders such as anxiety disorder and schizophrenia. However, little evidence supported an association between trauma and risk of depression, bipolar disorder, sleep disorder, and eating disorder. Our findings offered novel insights into the trauma-mediated development mechanism of psychiatric disorders, and psychological intervention to patients with trauma may be an effective prevention strategy for psychological diseases.
Abstract
Background
Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important risk factors for hepatocellular carcinoma. However, their effect on other hepatobiliary cancers, ...such as biliary tract cancers (BTCs), is not well established. We aimed to investigate associations between HBV or HCV infection and BTCs risk by conducting a systematic review and meta-analysis.
Methods
We searched PubMed to identify all relevant articles published before June 9, 2021. Meta-analysis was performed to calculate pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). The meta-analysis was evaluated by heterogeneity testing, sensitivity analyses, and publication bias assessment.
Results
In total, 48 articles involving 69,723 cases and 4,047,574 controls were obtained to calculate the associations between HBV or HCV infection and the risk of BTCs. We found that both HBV and HCV infections were associated with the risk of BTCs, with pooled ORs of 2.16 (95% CI 1.73–2.69) and 2.12 (95% CI 1.62–2.77), respectively. Subgroup analyses by ethnicity suggested that HBV infection could increase the risk of BTCs in both Asian (OR = 2.29, 95% CI 1.76–2.97) and Caucasian (OR = 1.80, 95% CI 1.18–2.75) populations. In addition, HCV infection resulted in a higher increased risk of BTCs in Caucasian populations than in Asian populations (OR = 3.93 vs
.
1.51,
P
= 0.014). In particular, significantly increased risks of intrahepatic cholangiocarcinoma (ICC) were identified in individuals with HBV (OR = 3.96, 95% CI 3.05–5.15) or HCV infection (OR = 2.90, 95% CI 2.07–4.08).
Conclusions
This study suggests that both HBV and HCV infections are risk factors for BTCs, particularly ICC, highlighting the necessity of cancer screening for BTCs in patients with either HBV or HCV infection.
Background Cholangiocarcinoma (CCA) is a typical inflammation-induced malignancy, and elevated serum interleukin-6 (IL-6) levels have been reported to be linked to the onset and progression of CCA. ...We aim to investigate the potential prognostic value of the IL-6 pathway for CCA. Methods We detected the expressions of IL-6, IL-6R, glycoprotein (gp130), C-reactive protein (CRP), Janus kinase 2 (JAK2), and signal transducer and activator of transcription 3 (STAT3) in CCA tissue microarray using multiplex immunofluorescence. Furthermore, the clinical associations and prognostic values were assessed. Finally, single-cell transcriptome analysis was performed to evaluate the expression level of IL-6 pathway genes in CCA. Results The results revealed that the expression of IL-6 was lower, while the expression of STAT3 was higher in tumor tissues compared to normal tissues. Especially in tumor microenvironment, the expression of IL-6 pathway genes was generally downregulated. Importantly, gp130 was strongly correlated with JAK2 in tumor tissues, while it was moderately correlated with JAK2 in normal tissue. Although none of the gene expressions were directly associated with overall survival and disease-free survival, our study found that IL-6, IL-6R, CRP, gp130, and JAK2 were inversely correlated with vascular invasion, which is a risk factor for poor prognosis in patients with CCA. Conclusion The findings from this study suggest that the IL-6 signaling pathway may have a potential prognostic value for CCA. Further investigation is needed to understand the underlying molecular mechanisms of the IL-6 pathway in CCA.
A clinical testing cohort was used to gain a broader understanding of the spectrum of tumors associated with germline p53 mutations to aid clinicians in identifying high-risk families.
Full ...sequencing of the coding exons (2 to 11) and associated splice junctions of the p53 gene was performed on 525 consecutive patients whose blood samples were submitted for diagnostic testing. Clinical features of p53 germline carriers in this cohort were characterized, clinical referral schemes based on reported p53-associated family phenotypes were evaluated, and practical mutation prevalence tables were generated.
Mutations were identified in 91 (17%) of 525 patients submitted for testing. All families with a p53 mutation had at least one family member with a sarcoma, breast, brain, or adrenocortical carcinoma (ACC). Every individual with a choroid plexus tumor (eight of eight) and 14 of 21 individuals with a childhood ACC had a mutation regardless of family history. Based on reported personal and family history, 95% of patients (71 of 75) with a mutation met either classic Li Fraumeni syndrome (LFS) or Chompret criteria. A simplified prevalence table provides a concise summary of individual and family characteristics associated with p53 mutations.
This is, to our knowledge, the largest single report of diagnostic testing for germline p53 mutations, yielding practical mutation prevalence tables and suggesting clinical utility of classic LFS and Chompret criteria for identifying a subset of cancer-prone families with p53 germline mutations, with important implications for diagnosis and management.
Purpose
Antihypertensive medication is an effective way to control blood pressure. However, some studies reported that it may affect patients’ sleep quality during the treatment. Due to the ...inconsistency of present results, a comprehensive systematic review and network meta-analysis are needed.
Methods
Electronic databases (MEDLINE, EMBASE, WEB OF SCIENCE, PUBMED) were searched up to April 10th, 2021 including no restriction of publication status. Randomized controlled trials (RCTs) or quasi-experimental studies or cohort studies were eligible. The network meta-analysis was used within a Bayesian framework.
Results
Finally, 16 publications (including 12 RCTs and 4 quasi-experimental studies) with 404 subjects were included in this study. Compared to placebo, the results of the network meta-analysis showed that diuretics were effective in improving sleep apnea with a mean difference (MD) of − 15.47 (95% confidence interval CI: − 23.56, − 6.59) which was consistent with the direct comparison result (MD: − 17.91; 95% CI − 21.60, − 14.23). In addition, diuretics were effective in increasing nocturnal oxygen saturation with an MD of 3.64 (95% CI 0.07, 7.46). However, the effects of β-blockers, calcium channel blockers, angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, and the others on sleep apnea were not statistically significant. Additionally, the effects of antihypertensive medication on the total sleep time (min), rapid eye movement (%), and sleep efficiency (%) were not statistically significant.
Conclusion
Our study found that diuretics could effectively reduce the severity of sleep apnea in hypertensive patients. However, the effects of antihypertensive drugs on sleep characteristics were not found.
Genetic studies have linked polymorphisms in the interleukin 6 receptor (
) gene to the risk of multiple human diseases and phenotypes, yet have reported inconsistent results. We aimed to synthesize ...current knowledge of variants in the
gene on the risk of diseases and phenotypes.
We searched the Medline and Embase databases to identify relevant publications. Meta-analysis was performed utilizing DerSimonian and Laird random-effects model. We also graded cumulative evidence for significant associations. Furthermore, phenome-wide analyses and functional annotations were performed for variants with strong evidence.
We included 155 studies for evaluating the associations between 80 polymorphisms in the
gene and the risk of 102 human diseases and 98 phenotypes. We conducted 58 main meta-analyses, and 41 significant associations were identified. Strong evidence was assigned to 29 associations that investigated ten variants (rs2228145, rs4129267, rs7529229, rs4537545, rs7518199, rs4845625, rs4553185, rs4845618, rs4845371, and rs6667434) related to the risk of four cardiovascular diseases (coronary heart disease, coronary artery disease, atherosclerosis, and abdominal aortic aneurysms), four inflammatory diseases (rheumatoid arthritis, Crohn's disease, dermatitis, and asthma), and concentration of four phenotypes (C-reactive protein, fibrinogen, IL-6, and sIL-6R). Furthermore, phenome-wide analysis verified that rs2228145 associated with asthma and dermatitis risk. Functional analyses indicated that these polymorphisms fall within exon, enhancer regions.
Our study comprehensively summarizes current data on the genetic architecture of the
gene and highlights the pharmacological targeting potential of IL-6R on cardiovascular and inflammatory diseases.
Hypertension (HTN) is a growing contributor to the global disease burden, and it is prevalent among people living at high altitudes (H-ALTs). This study aimed to explore the relationship between ...altitude and the prevalence of HTN among inhabitants living at H-ALTs. We searched electronic databases, including PubMed, Embase, and Web of Science, up to April 30, 2022. The quality of included studies was assessed using the Joanna Briggs Institute (JBI) checklist for prevalence studies. A total of 1273 articles were screened, and 32 studies (86,487 participants) were eligible for further analyses. The pooled prevalence among highlanders was 28.7%. General additive model (GAM)-based meta-regression analysis was conducted to explore the association between altitude and the prevalence of HTN. A curve-shaped line was found between altitude and the prevalence of HTN (β = 0.998, p = 0.039) after adjusting for factors including publication year, sample size, age, sex, ethnic group, body mass index (BMI), smoking and alcohol consumption. The turning point was observed at 3300 m. The predictive parameter indicated that the smoothness and goodness of model fit were good (GCV = 0.014, R
= 0.60, respectively). The findings may provide clues for further mechanistic studies that can improve HTN prevention among highlanders.
Genetic studies have linked the VTI1A‐TCF7L2 region with risk of multiple cancers. However, findings from these studies were generally inconclusive. We aimed to provide a synopsis of current ...understanding of associations between variants in the VTI1A‐TCF7L2 region and cancer susceptibility. We conducted a comprehensive research synopsis and meta‐analysis to evaluate associations between 17 variants in this region and risk of seven cancers using data from 32 eligible articles totaling 224,656 cancer cases and 324,845 controls. We graded cumulative evidence of significant associations using Venice criteria and false‐positive report probability tests. We also conducted analyses to evaluate potential function of these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project. Eight variants showed a nominally significant association with risk of individual cancer (p < 0.05). Cumulative epidemiological evidence of an association was graded as strong for rs7903146 odds ratio (OR) = 1.05, p = 4.13 × 10−5 and rs7904519 (OR = 1.07, p = 2.02 × 10−14) in breast cancer, rs11196172 (OR = 1.11, p = 2.22 × 10−16), rs12241008 (OR = 1.13, p = 1.36 × 10−10) and rs10506868 (OR = 1.10, p = 3.98 × 10−9) in colorectal cancer, rs7086803 in lung cancer (OR = 1.30, p = 3.54 × 10−18) and rs11196067 (OR = 1.18, p = 3.59 × 10−13) in glioma, moderate for rs12255372 (OR = 1.12, p = 2.52 × 10−4) in breast cancer and weak for rs7903146 (OR = 1.11, p = 0.007) in colorectal cancer. Data from ENCODE suggested that seven variants with strong evidence and other correlated variants might fall within putative functional regions. Collectively, our study provides summary evidence that common variants in the VTI1A and TCF7L2 genes are associated with risk of breast, colorectal, lung cancer and glioma and highlights the significant role of the VTI1A‐TCF7L2 region in the pathogenesis of human cancers.
What's new?
The genes that code for the vesicle transport through interaction with t‐SNAREs 1A VTI1A and the transcription factor 7‐like 2 TCF7L2 may be associated with multiple cancers, but previous studies have been largely inconclusive. In this large meta‐analysis of data from 224,656 cancer cases and 324,845 controls, the authors found that multiple genetic variants in the VTI1A‐TCF7L2 region of chromosome 10 were strongly associated with breast, colorectal, lung cancer and glioma, although several different molecular mechanisms may be involved. These results support a role for these gene loci in tumor formation and progression, and may suggest potential therapeutic targets.
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