Association between estimated pulse wave velocity and all-cause death in patients with heart failure.

BACKGROUND: Arteriosclerosis has been proven to be a risk factor for the development of heart failure and readmission. ePWV is a novel non-invasive and simple indicator of arterial stiffness, and this study aims to investigate its relationship with all-cause mortality rate in patients with heart failure. METHODS: This study is a cohort study that included 1272 patients with heart failure from NHANES data from 1999 to 2018. The ePWV was divided into three groups, and the cumulative mortality rate of heart failure patients was calculated using KM survival curves. The relationship between ePWV and all-cause mortality rate in heart failure patients was represented by a smoothed curve fitting. COX regression analysis was used to assess the association between ePWV and all-cause mortality rate in heart failure patients. RESULTS: The average age of the study population was 67.8 ± 12.6 years, with 862 males and 650 females. During the 12-month follow-up period, there were 790 cases of all-cause mortality. Cox regression analysis was used to validate the relationship between ePWV and all-cause mortality rate in patients with heart failure. Patients with higher levels of ePWV tended to have a higher all-cause mortality rate. After adjustment for multiple factors, an increase in ePWV was positively associated with all-cause mortality rate (HR = 1.17, 95% confidence interval (CI): (1.12, 1.22)). Compared to the lowest tertile, the multivariable-adjusted HR and 95% CI for the highest tertile of ePWV were 1.81 (95% CI: (1.45, 2.27)). Additionally, a smoothed curve fitting was used to observe the relationship between ePWV and mortality rate, where the curve demonstrated a positive correlation between ePWV and all-cause mortality rate. Furthermore, KM survival curves indicated that all-cause mortality rate increased with the increase in ePWV. Subgroup analysis suggested a correlation between ePWV and mortality rate. CONCLUSION: Our study shows that ePWV is positively associated with all-cause mortality in patients with heart failure.

Association between estimated pulse wave velocity and all-cause mortality in patients with coronary artery disease: a cohort study from NHANES 2005-2008.

BACKGROUND: Arterial stiffness has been shown to be an independent risk factor for adverse events and all-cause mortality in patients. Although PWV is the gold standard for pulse wave velocity, its application in clinical practice is limited by the high cost and complexity. ePwv is a new, simple, non-invasive indicator of arterial stiffness. The aim of this study was to assess the relationship between ePwv and all-cause mortality in patients with coronary artery disease. METHODS: This is a cohort study, selected from NHANES 2005 to 2008, 402 patients with coronary artery disease were included. The ePWV was divided into two groups and KM survival curves were used to calculate cumulative mortality in patients with coronary artery disease. Restricted cubic spline were used to represent the relationship between ePWV and all-cause mortality in patients with coronary artery disease. Cox regression was used to diagnose the relationship between ePwv and all-cause mortality. RESULTS: The mean age of the study subjects was 68.5 ± 11.8 years, of which 282 (70.1%) were men and 120 (29.9%) were women. During 180 months of follow-up, 160 all-cause mortality occurred. KM survival curves indicated that all-cause mortality increased with increasing ePWV. The relationship between ePWV and all-cause mortality in patients with coronary artery disease was verified by cox models. Patients in higher ePWV tertile tended to have higher all-cause mortality. After complete multivariate adjustment, an increase in ePWV was positively associated with all-cause mortality (HR = 1.180, 95% confidence interval (CI): 1.056-1.320). The multivariate-adjusted HR and 95% CI for the highest ePWV tertile was 1.582 (95% CI: 0.968-2.587) compared to the lowest tertile. In addition, the association between ePWV and mortality was visualized employing restricted spline curves, in which we found curves indicating a possible threshold for the effect of ePWV on all-cause mortality, with HR less than 1 when ePWV was less than 11.15 m/s; thereafter, there was a tendency for HR to increase with enhanced ePWV. Subgroup analysis showed that the correlation between ePWV and mortality persisted in population subgroups. CONCLUSION: Our findings suggest that higher ePWV is associated with increased all-cause mortality in patients with coronary artery disease, particularly when ePWV exceeds 11.15 m/s.

Association between estimated pulse wave velocity and risk of diabetes: A large sample size cohort study.

BACKGROUND AND AIM: Estimated pulse wave velocity (ePWV) measurements have good agreement with PWV measurements. However, the relationship between ePWV and the risk of new-onset diabetes remains unclear. Therefore, this study aimed to investigate whether ePWV was associated with new-onset diabetes. METHODS AND RESULTS: Based on a secondary analysis of the Chinese Rich Health Care Group's cohort study, 211,809 participants who met the criteria were enrolled and divided into four groups based on the ePWV quartiles. Diabetes events are of interest as a result of the study. Over a mean follow-up of 3.12 years, 3000 male (1.41%) and 1173 female (0.55%) patients were diagnosed with new-onset diabetes. The cumulative incidence curves based on quartile subgroups showed that the Q4 group had a significantly higher overall incidence of diabetes than the other subgroups. A multivariate Cox regression analysis showed that ePWV was an independent predictor of new-onset diabetes (hazard ratio, 1.233; 95% confidence interval, 1.198-1.269; P < 0.001). The receiver operating characteristic curve showed that the predictive value was higher than for age and blood pressure. The ePWV was treated as a continuous variable using MaxStat, which identified that the best cut-off point for diabetes risk was 8.47 m/s. A stratified analysis showed that the association between ePWV and the risk of diabetes remained significant in multiple strata. CONCLUSIONS: An elevated ePWV was independently associated with an increased risk of developing diabetes in Chinese adults. Thus, ePWV may be a reliable indicator of the risk of early diabetes.

Detecting Genetic Variation of Colonizing Streptococcus agalactiae Genomes in Humans: A Precision Protocol.

Deciphering the genotypic diversity of within-individual pathogens and verifying the evolutionary model can help elucidate resistant genotypes, virulent subpopulations, and the mechanism of opportunistic pathogenicity. However, observed polymorphic mutations (PMs) are rare and difficult to be detected in the "dominant-lineage" model of bacterial infection due to the low frequency. The four pooled group B Streptococcus (GBS) samples were collected from the genital tracts of healthy pregnant women, and the pooled samples and the isogenic controls were genomically sequenced. Using the PMcalling program, we detected the PMs in samples and compared the results between two technical duplicates, GBS-M001T and GBS-M001C. Tested with simulated datasets, the PMcalling program showed high sensitivity especially in low-frequency PMs and reasonable specificity. The genomic sequence data from pooled samples of GBS colonizing carrier pregnant women were analyzed, and few high-frequency PMs and some low-frequency PMs were discovered, indicating a dominant-lineage evolution model. The PMs mainly were nonsynonymous and enriched in quorum sensing, glycolysis/gluconeogenesis, ATP-binding cassette (ABC) transporters, etc., suggesting antimicrobial or environmental selective pressure. The re-analysis of the published Burkholderia dolosa data showed a diverse-community model, and only a few low-frequency PMs were shared between different individuals. Genes of general control non-repressible 5-related N-acetyltransferases family, major facilitator superfamily (MFS) transporter, and ABC transporter were positive selection candidates. Our findings indicate an unreported nature of the dominant-lineage model of GBS colonization in healthy women, and a formerly not observed mutation pool in a colonized microbial community, possibly maintained by selection pressure.

Diagnosis of severe Chlamydia psittaci pneumonia by metagenomic next-generation sequencing: 2 case reports.

Psittacosis is a infectious disease caused by Chlamydia psittaci (C. psittaci), which presents as pneumonia in humans. The diagnosis of psittacosis is challenging, however, Metagenomic next-generation sequencing (MNGS) is very efficient. Herein we documented the clinical characteristics of two patients with severe C. psittaci pneumonia who were admitted to the Intensive Care Unit. C. psittaci nucleic acid sequences were detected by MNGS of bronchoalveolar lavage fluid from both patients. Doxycycline was administered and the treatment was effective. Implementation of MNGS is helpful for the early identification of pathogens, shortening the diagnosis and treatment time, and improving the prognosis of patients.

OAB-14, a bexarotene derivative, improves Alzheimer's disease-related pathologies and cognitive impairments by increasing ß-amyloid clearance in APP/PS1 mice.

The pathogenesis of Alzheimer's disease (AD) is complex, though the clinical failures of anti-AD candidates targeting Aß production (such as ß- and γ-secretase inhibitors) make people suspect the Aß hypothesis, in which the neurotoxicity of Aß is undoubtedly involved. According to studies, >95% of AD patients with sporadic AD are primarily associated with abnormal Aß clearance. Therefore, drugs that increase Aß clearance are becoming new prospects for the treatment of AD. Here, the novel small molecule OAB-14, designed using bexarotene as the lead compound, significantly alleviated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) transgenic mice after administration for 15 days or 3 months. OAB-14 rapidly cleared 71% of Aß by promoting microglia phagocytosis and increasing IDE and NEP expression. This compound also attenuated the downstream pathological events of Aß accumulation, such as synaptic degeneration, neuronal loss, tau hyperphosphorylation and neuroinflammation in APP/PS1 mice. Moreover, OAB-14 had no significant effect on body weight or liver toxicity after acute and chronic treatment. OAB-14 was well tolerated and its maximum-tolerated dose in mice was >4.0 g/kg. Based on these findings, OAB-14 represents a promising new candidate for AD treatment.

Neuron-Derived ADAM10 Production Stimulates Peripheral Nerve Injury-Induced Neuropathic Pain by Cleavage of E-Cadherin in Satellite Glial Cells.

BACKGROUND: Increasing evidence suggests the potential involvement of metalloproteinase family proteins in the pathogenesis of neuropathic pain, although the underlying mechanisms remain elusive. METHODS: Using the spinal nerve ligation model, we investigated whether ADAM10 proteins participate in pain regulation. By implementing invitro methods, we produced a purified culture of satellite glial cells to study the underlying mechanisms of ADAM10 in regulating neuropathic pain. RESULTS: Results showed that the ADAM10 protein was expressed in calcitonin gene-related peptide (CGRP)-containing neurons of the dorsal root ganglia, and expression was upregulated following spinal nerve ligation surgery invivo. Intrathecal administration of GI254023X, an ADAM10 selective inhibitor, to the rats one to three days after spinal nerve ligation surgery attenuated the spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia. Intrathecal injection of ADAM10 recombinant protein simulated pain behavior in normal rats to a similar extent as those treated by spinal nerve ligation surgery. These results raised a question about the relative contribution of ADAM10 in pain regulation. Further results showed that ADAM10 might act by cleaving E-cadherin, which is mainly expressed in satellite glial cells. GI254023X reversed spinal nerve ligation-induced downregulation of E-cadherin and activation of cyclooxygenase 2 after spinal nerve ligation. ß-catenin, which creates a complex with E-cadherin in the membranes of satellite glial cells, was also downregulated by spinal nerve ligation surgery in satellite glial cells. Finally, knockdown expression of ß-catenin by lentiviral infection in purified satellite glial cells increased expression of inducible nitric oxide synthase and cyclooxygenase 2. CONCLUSION: Our findings indicate that neuron-derived ADAM10 production stimulates peripheral nerve injury-induced neuropathic pain by cleaving E-cadherin in satellite glial cells.

The genome of serotype VI Streptococcus agalactiae serotype VI and comparative analysis.

Streptococcus agalactiae (GBS) causes serious infections in humans and other species. A total of 25 complete GBS genomes, including the first sequenced serotype VI genome (GBS-M002), were compared in this study. The power law model suggested that the pan-genome of GBS is open, with approximately 1300 genes in the core genome of GBS, accounting for approximately 60% of the average genome content. GBS-M002 has 73 specific genes and is one of the five strains containing >60 specific genes. Based on COG (Cluster of Orthologous Groups of proteins) functional classification, 24% of the genes related to defense mechanisms are specific among the strains. A phylogenetic tree shows that GBS-M002 is closely related to certain strains of serotypes III and V from humans and to isolates of unknown serotype from dog and bovine hosts, suggesting the universal infection potential of GBS from humans to other mammal and fish hosts.

Optimized Exon-Exon Junction Library and its Application on Rodents' Brain Transcriptome Analysis

ABSTRACT Background: Alternative splicing (AS), which plays an important role in gene expression and functional regulation, has been analyzed on genome-scale by various bioinformatic approaches based on RNA-seq data. Compared with the huge number of studies on mouse, the AS researches approaching the rat, whose genome is intermedia between mouse and human, were still limited. To enrich the knowledge on AS events in rodents' brain, we perfomed a comprehensive analysis on four transcriptome libraries (mouse cerebrum, mouse cerebellum, rat cerebrum, and rat cerebellum), recruiting high-throughput sequencing technology. An optimized exon-exon junction library approach was introduced to adapt the longer RNA-seq reads and to improve mapping efficiency. Results: In total, 7,106 mouse genes and 2,734 rat genes were differentially expressed between cerebrum and cerebellum, while 7,125 mouse genes and 1,795 rat genes exhibited varieties on transcript variant level. Only half of the differentially expressed exon-exon junctions could be reflected at gene expression level. Functional cluster analysis showed that 32 pathways in mouse and 9 pathways in rat were significantly enriched, and 6 of them were in both. Interestingly, some differentially expressed transcript variants did not show difference on gene expression level, such as PLCβ1 and Kcnma1. Conclusion: Our work provided a case study of a novel exon-exon junction strategy to analyze the expression of genes and isoforms, helping us understand which transcript contributes to the overall expression and further functional change.

A Comprehensive Analysis of the Transcriptomes of Marssonina brunnea and Infected Poplar Leaves to Capture Vital Events in Host-Pathogen Interactions.

BACKGROUND: Understanding host-pathogen interaction mechanisms helps to elucidate the entire infection process and focus on important events, and it is a promising approach for improvement of disease control and selection of treatment strategy. Time-course host-pathogen transcriptome analyses and network inference have been applied to unravel the direct or indirect relationships of gene expression alterations. However, time series analyses can suffer from absent time points due to technical problems such as RNA degradation, which limits the application of algorithms that require strict sequential sampling. Here, we introduce an efficient method using independence test to infer an independent network that is exclusively concerned with the frequency of gene expression changes. RESULTS: Highly resistant NL895 poplar leaves and weakly resistant NL214 leaves were infected with highly active and weakly active Marssonina brunnea, respectively, and were harvested at different time points. The independent network inference illustrated the top 1,000 vital fungus-poplar relationships, which contained 768 fungal genes and 54 poplar genes. These genes could be classified into three categories: a fungal gene surrounded by many poplar genes; a poplar gene connected to many fungal genes; and other genes (possessing low degrees of connectivity). Notably, the fungal gene M6_08342 (a metalloprotease) was connected to 10 poplar genes, particularly including two disease-resistance genes. These core genes, which are surrounded by other genes, may be of particular importance in complicated infection processes and worthy of further investigation. CONCLUSIONS: We provide a clear framework of the interaction network and identify a number of candidate key effectors in this process, which might assist in functional tests, resistant clone selection, and disease control in the future.

Activating transcription factor 4 modulates BDNF release from microglial cells.

Pathogenic pain is a common sign of many diseases. The mechanism is unclear. Activating transcription factor 4 (ATF4) plays a critical role in cell activation. Brain-derived neurotrophic factor (BDNF) is an important molecule in pathogenic pain. This study aims to investigate the role of ATF4 in inducing BDNF release from microglial cells. In this study, mouse microglial cells were cultured. The levels of BDNF in the culture medium were determined by enzyme-linked immunosorbent assay. Overexpression of ATF4 in microglial cells was performed by gene transfection. The apoptosis of microglial cells was assessed by flow cytometry. The results showed that microglial cells expressed ATF4 and protease-activated receptor-2 (PAR2). BDNF was detectable in the culture medium of microglial cells, which was significantly increased in the ATF4-overexpressing microglial cells. The ATF4-overexpressing microglial cells showed a high frequency of apoptotic cells, which could be inhibited by exposure to the PAR2 agonist tryptase in the culture. The tryptase-treated ATF4-overexpressing microglial cells kept higher secretion of BDNF. We conclude that the activation of ATF4 can increase BDNF release from microglial cells.

MicroRNA-212 displays tumor-promoting properties in non-small cell lung cancer cells and targets the hedgehog pathway receptor PTCH1.

Dysexpression of microRNAs has been found in many tumors, including lung cancer. The hedgehog (Hh) signaling pathway plays an important role during normal development, and the abnormal regulation of its members has also been related to many tumors. However, little is known about the relationship between microRNA and the Hh pathway. In this paper, we report microRNA-212 (miR-212) playing a role in non-small cell lung cancer (NSCLC) and targeting PTCH1, a receptor of the Hh pathway. We found that miR-212 was up-regulated when cells were treated with 4ß-12-O-tetradecanoylphorbol-13-acetate (TPA). We ectopically expressed miR-212 in NSCLC cell lines to examine the influence of miR-212 overexpression. The results showed that overexpression of miR-212 in NSCLC cells promoted cell cycle progression and cell proliferation, migration, and invasion. The promoting effects of miR-212 on cell proliferation, migration, and invasion were partially reversed by the miR-212 inhibitor anti-miR-212. These results suggested that miR-212 might have tumor-promoting properties. Potential targets of miR-212 were predicted, and we showed tumor suppressor PTCH1 was a functional target of miR-212. PTCH1 may be responsible for the effect of miR-212 on cell proliferation. Altogether, our results indicated that miR-212 was involved in tumorigenesis, and the oncogenic activity of miR-212 in NSCLC cells was due, in part, to suppression of PTCH1.

Cx31.1 acts as a tumour suppressor in non-small cell lung cancer (NSCLC) cell lines through inhibition of cell proliferation and metastasis.

Reduced connexin expression and loss of gap junction function is a characteristic of many cancers, including lung cancer. However, there are little reports about the relation between Cx31.1 and lung cancer. This study was conducted to investigate the effect of Cx31.1 on non-small cell lung cancer (NSCLC). We found that the Cx31.1 was down-regulated in NSCLC cell lines, and the expression levels were reversely related with their metastatic potential. We ectopically expressed Cx31.1 in H1299 NSCLC cell line to examine the influence of Cx31.1 overexpression. The results showed that overexpression of Cx31.1 in H1299 cells reduced cell proliferation, induced a delay in the G(1) phase, inhibited anchorage-independent growth and suppressed cell migration and invasion. The cell cycle delay and cell migration and invasion suppressive effects of Cx31.1 were partially reversed by siRNA targeting mRNA of Cx31.1. Moreover, xenografts of Cx31.1 overexpressing H1299 cells showed reduced tumourigenicity. These results suggested that Cx31.1 has tumour-suppressive properties. Further investigation indicated that cyclin D3 may be responsible for Cx31.1-induced G(1) phase delay. Importantly, Cx31.1 increased the expression of epithelial markers, such as cytokeratin 18, and decreased expression of mesenchymal markers, such as vimentin, indicating a Cx31.1-mediated partial shift from a mesenchymal towards an epithelial phenotype. We concluded that Cx31.1 inhibit the malignant properties of NSCLC cell lines, the mechanisms under this may include regulation of EMT.

Varied pathways of stage IA lung adenocarcinomas discovered by integrated gene expression analysis.

BACKGROUND: Discovery of the progression-associated genes and pathways in lung adenocarcinoma (LAD) has important implications in understanding the molecular mechanism of tumor development. However, few studies had been performed to focus on the changes of pathways in lung adenocarcinoma development using microarray expression profile. RESULT: We performed a meta-analysis of 4 LAD microarray datasets encompassing 353 patients to reveal differentially expressed genes (DEGs) between normal lung tissues and LAD of different stages. Overall, 1 838 genes were found to be dys-regulated, and the adipogenesis, circadian rhythm, and Id pathways were significantly changed. Interestingly, most of the genes from the same gene family (such as Interleukin receptor, Matrix metallopeptidase, Histone cluster and Minichromosome maintenance complex component families) were found to be up-regulated (or down-regulated). Real-time PCR (qRT-PCR) was applied to validate the expression of randomly selected 18 DEGs in LAD cell lines. In the pathway analysis among stages, Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways, which were involved in cancer cell proliferation and metastasis, were showed to be significantly regulated in stages other than IA. CONCLUSION: Genes involved in adipogenesis and Id pathways might play important roles in development of LADs. The similar trend of expression of the gene family members suggested coordinate regulation in tumor progression. Three pathways (Oxidative stress, Glycolysis/Gluconeogenesis and Integrin-mediated cell adhesion pathways) significantly regulated in stages other than stage IA suggested that genes and pathways conferring invasive character might be activated in the preinvasive stage IB, while the Oxidative stress and the Glycolysis/Gluconeogenesis pathways might have strong connections to cisplatin-based chemotherapy. The insignificantly regulated three pathways in stage IA might be used in early-stage detection of LAD.

Speeding for fun? Exploring the speeding behavior of riders of heavy motorcycles using the theory of planned behavior and psychological flow theory.

This paper focuses on a special segment of motorcyclists in Taiwan--riders of heavy motorcycles--and investigates their speeding behavior and its affecting factors. It extends the theory of planned behavior (TPB) to explore motorcyclist speeding behavior by including the variables of psychological flow theory. The levels of sensation-seeking and riding experience are also used as grouping variables to investigate group differences from the influences of their affecting factors on speeding behavior. The results reveal that the psychological flow variables have greater predictive power in explaining speeding behavior than the TPB variables, providing useful insights into the unique nature of this group of motorcyclists, who are more prone to engage in speeding. Group differences with regard to both sensation-seeking and rider experience in speeding behavior are highlighted, and the implications of the findings are discussed.

Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha polypeptide 2 gene (SRD5A2) and risk of prostate cancer.

The steroid-5-alpha-reductase, alpha polypeptide 2 (SRD5A2) gene plays a crucial role in androgen metabolism pathway in human prostate. It encodes SRD5A2 enzyme, which catalyses testosterone to dihydrotestosterone (DHT). DHT is the main active structure binding with androgen receptor (AR). After the activation of AR, it further regulates a series of target genes in androgen metabolism pathway. However, no clear consensus has been reached on the association between the SRD5A2 V89L, A49T and TA repeat polymorphisms and prostate cancer (PCa) risk. Thus, we performed a meta-analysis of 31 association studies with 14,726 PCa cases and 15,802 controls. We found no association between PCa and 89L compared with 89V allele [odds ratio (OR) = 1.02, 95% confidence interval (CI) 0.98-1.06, P(heterogeneity) = 0.44]. The 49T allele showed a significantly elevated effect on the high stage (Stages III-IV) of PCa risk both under the dominant genetic model (OR = 2.13, 95% CI 1.44-3.15, P(heterogeneity) = 0.65) and in the contrast T versus A allele (OR = 2.06, 95% CI 1.41-3.02, P(heterogeneity) = 0.69). There was a significantly decreased association between PCa and long TA repeat as compared versus short TA repeat (OR = 0.86, 95% CI 0.74-1.00, P(heterogeneity) = 0.79). No significant between-study heterogeneity was found in all subjects under four genetic models (dominant model, recessive model, allele comparison and homozygosity comparison) for these three polymorphisms, respectively, so the fixed effects model was used to pool the result. Our result indicated that carriers of 49T might improve the risk of PCa in higher stages (Stages III-IV), carriers of long TA repeat might decrease the risk of PCa and 89L may not be an important risk factor for PCa. However, due to the limited sample sizes, this meta-analysis did not achieve sufficiently conclusive results. Still more well-designed studies should be performed to clarify the role of these three polymorphisms in the development of PCa.

Hydrogen-rich saline protects against spinal cord injury in rats.

In the present study, we examined the mechanisms of hydrogen-rich saline, a reported therapeutic antioxidant, in the treatment of acute spinal cord contusion injury. Male Sprague-Dawley rats were used to produce a standardized model of contuses spinal cord injury (125 kdyn force). Hydrogen-rich saline was injected intraperitoneally (5 ml/kg) immediately, and at 24 and 48 h after injury. All rats were sacrificed at 72 h after spinal cord injury (SCI). Apoptotic cell death, oxidative stress, inflammation, level of Brain derived neurotrophic factor (BDNF) were evaluated. In addition, locomotor behavior was assessed using the Basso, Beattice and Bresnahan (BBB) scale. We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of BDNF. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.

TP53 Arg72Pro polymorphism and lung cancer risk: a meta-analysis.

No clear consensus has been reached on the TP53 Arg72Pro polymorphism (G12139C) and lung cancer risk. Thus, a meta-analysis was conducted to summarize the possible association. There was no statistical association between 12139C (Pro allele) and lung cancer risk in Caucasians compared with 12139G allele. However, the association was observed in all subjects (9,387 patients and 9,922 controls, p=0.04, OR=1.08, 95% CI 1.00-1.17), as well as in Asians (p=0.0004, OR=1.14, 95% CI 1.06-1.22). The association was also found in Asians under recessive genetic model (p<0.00001, OR=1.37, 95% CI 1.20-1.57) and homozygote comparison (CC vs. GG) (p<0.0001, OR=1.34, 95% CI 1.16-1.56). 12139C allele might increase the lung adenocarcinoma risk compared with 12139G allele (p=0.01, OR=1.11, 95% CI 1.02-1.21), and the effect was also found under recessive genetic model (p=0.003, OR=1.28, 95% CI 1.09-1.50) and homozygote comparison (CC vs. GG) (p=0.007, OR=1.28, 95% CI 1.07-1.52). There was an elevated association between the 12139C and the stage I lung cancer under dominant genetic model (p=0.04, OR=1.48, 95% CI 1.02-2.16), but no association was observed in other stages. No association of smoking was found between 12139C allele and lung cancer under recessive genetic model. Our result indicated that 12139C might increase the risk of lung cancer under recessive genetic model in adenocarcinoma, in Asians, and in lung cancer stage I. More studies stratified for lung cancer stage-genotyping interaction should be performed to clarify the role of TP53 Arg72Pro polymorphism in the development of lung cancer.

A meta-analysis of DNA repair gene XPC polymorphisms and cancer risk.

Polymorphisms (A33512C, C21151T and PAT -/+) of the xeroderma pigmentosum group C (XPC) were shown to contribute to genetic susceptibility to cancer. However, association studies on these polymorphisms in cancer have shown conflicting results. Thus, we performed a meta-analysis. Overall, there was no significant association between 33512C (9,091 patients and 11,553 controls) and cancer risk. No significant association was found in stratification analysis by tumor sites and ethnicities except an elevated lung cancer risk under the recessive genetic model in all subjects [P = 0.04, odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.00-1.45, P (heterogeneity) = 0.88]. There was no significant association between 21151T (5,227 patients and 5,959 controls) and cancer risk in all subjects but an increased cancer risk in Caucasians under the recessive genetic model (P = 0.006, OR = 1.45, 95% CI 1.11-1.90, P (heterogeneity) = 0.75) and homozygote comparison (P = 0.02, OR = 1.41, 95% CI 1.07-1.81, P (heterogeneity) = 0.41). It might be that 21151T increases bladder cancer risk under the recessive genetic model (P = 0.02, OR = 1.49, 95% CI 1.06-2.09, P (heterogeneity) = 0.47) and homozygote comparison (P = 0.02, OR = 1.49, 95% CI 1.05-2.11, P (heterogeneity) = 0.23). There was no significant association between PAT + (4,600 patients and 4,866 controls) and cancer risk in all subjects. An increased cancer risk in Caucasians was found under the recessive genetic model (P = 0.02, OR = 1.20, 95% CI 1.03-1.40, P (heterogeneity) = 0.37) and homozygote comparison (P = 0.008, OR = 1.26, 95% CI 1.06-1.50, P (heterogeneity) = 0.13). The XPC PAT + allele might increase head and neck cancer risk (P = 0.02, OR = 1.29, 95% CI 1.04-1.59, P (heterogeneity) = 0.15). More studies based on larger, stratified, case-control population, especially studies investigate the combined effect of XPC A33512C, C21151T, and PAT, are required to further evaluate the role of these polymorphisms in different cancers.

Cytochrome P450 1A1 (CYP1A1) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis.

The cytochrome P450 1A1 gene (CYP1A1), encoding Phase I metabolic enzymes, appeared to be a candidate gene for breast cancer risk. However, studies on the association between polymorphisms in this gene and breast cancer have yielded conflicting results. We performed a meta-analysis to investigate the association with breast cancer of the CYP1A1 polymorphisms T3801C (9,316 cases and 12,714 controls) and A2455G (9,552 cases and 9,320 controls). In the genotype contrast of A2455G, both additive [GG vs AA, P = 0.04, fixed-effects OR 0.72; 95% CI (0.53-0.99), P = 0.95 for heterogeneity] and recessive [GG vs (GA + AA), P = 0.04, fixed-effects OR 0.73; 95% CI (0.53-0.99), P = 0.97 for heterogeneity] models produced significant results in east-Asians. In pre-menopausal women in a worldwide population, significant association between A2455G and breast cancer was also found using both models [additive model: P = 0.02, fixed-effects OR 0.52; 95% CI (0.29-0.92), P = 0.39 for heterogeneity; recessive model: P = 0.02, fixed-effects OR 0.51; 95% CI (0.29-0.90), P = 0.38 for heterogeneity]. Our meta-analysis suggests that an A2455G G/G genotype is associated with a trend of reduced breast cancer risk, both in east-Asian women and in pre-menopausal women worldwide, while the T3801C C allele might not be a risk factor for breast cancer. Larger scale primary studies are required to further evaluate the interaction of CYP1A1 polymorphisms and breast cancer risk in specific populations.