Interaction behaviors of sulfamethoxazole and microplastics in marine condition: Focusing on the synergistic effects of salinity and temperature.

Microplastics and antibiotics are two common pollutants in the ocean. However, due to changes of salinity and temperature in the ocean, their interaction are significantly different from that of fresh water, and the mechanism remains unclear. Here, the interactions of sulfamethoxazole (SMZ) and microplastics were studied at different temperatures and salinities. The saturation adsorption capacity of SMZ in polypropylene (PP), polyethylene (PE), styrene (PS), polyvinyl chloride (PVC), and synthetic resins (ABS) were highest at the temperature of 20 °C, with 0.118 ± 0.002 mg·g-1, 0.106 ± 0.004 mg·g-1, 0.083 ± 0.002 mg·g-1, 0.062 ± 0.007 mg·g-1 and 0.056 ± 0.003 mg·g-1, respectively. The effect of temperature reduction is more significant than temperature rise. The intraparticle diffusion model is appropriate to PP, when film diffusion model suited for PS. The salinity has a more significant effect than temperature on different microplastics, due to the electrostatic adsorption and iron exchange. With the increase in salinity from 0.05% to 3.5%, the adsorption capacity of microplastics on SMZ fell by 53.3 ± 5%, and there was no discernible difference of various microplastics. The hydrogen bond and π-π conjugation of microplastics play an important role in the adsorption of SMZ. These findings further deepen the understanding of the interaction between microplastics and antibiotics in the marine environment.

Nano and micro biomechanical analyses of the nucleus pulposus after in situ immobilization in rats.

Immobilization can lead to intervertebral disc degeneration. The biomechanical characteristics of such discs have not so far been investigated at the micro- or nanoscale, the level at which cells sense and respond to the surrounding environment. This study aimed to characterize changes in the elastic modulus of the collagen fibrils in the nucleus pulposus at the nanoscale and correlate this with micro-biomechanical properties of the nucleus pulposus after immobilization, in addition to observation of tissue histology and its gene expressions. An immobilization system was used on the rat tail with an external fixation device. The elastic modulus was measured using both nano and micro probes for atomic force microscopy after 4 and 8 weeks of immobilization. Histology of the tissue was observed following hematoxylin and eosin staining. Gene expression in the annulus fibrosus tissue was quantified using real-time reverse transcription-polymerase chain reaction. The elastic modulus of the collagen fibrils in the nucleus pulposus at the nanoscale increased from 74.07 ± 17.06 MPa in the control to 90.06 ± 25.51 MPa after 8 weeks (P = 0.007), and from 33.51 ± 9.33 kPa to 43.18 ± 12.08 kPa at the microscale (P = 0.002). After immobilization for 8 weeks, a greater number of cells were observed by histology to be aggregated within the nucleus pulposus. Collagen II (P = 0.007) and aggrecan (P = 0.003) gene expression were downregulated whereas collagen I (P = 0.002), MMP-3 (P < 0.001), MMP-13 (P < 0.001) and ADAMTs-4 (P < 0.001) were upregulated. Immobilization not only influenced individual collagen fibrils at the nanoscale, but also altered the micro-biomechanics and cell response in the nucleus pulposus. These results suggest that significant changes occur in intervertebral discs at both scales after immobilization, a situation about which clinicians should be aware when immobilization has to be used clinically.

Sensory nerves protect from the progression of early stage osteoarthritis in mice.

PURPOSE: Osteoarthritis (OA) is a chronic degenerative joint disease. Sensory nerves play an important role in bone metabolism and in the progression of inflammation. This study explored the effects of sensory nerve on OA progression at early stage in mice. MATERIALS AND METHODS: OA was induced via destabilization of the medial meniscus (DMM) in C57BL/6 mice. Sensory denervation was induced by subcutaneous injection of capsaicin (90 mg/kg) one week prior to DMM. One week after capsaicin injection, sensory denervation in the tibia was confirmed by immunofluorescent staining. Four weeks after DMM, micro-CT scans, histological analysis, and RT-PCR tests were performed to evaluate OA progression. RESULTS: Subcutaneous injection of capsaicin successfully induced sensory denervation in tibia. The Osteoarthritis Research Society International (OARSI) score and synovitis score of the capsaicin+DMM group were significantly higher than the score of the vehicle+DMM group. The BV/TV of the tibial subchondral bone in the capsaicin+DMM group was significantly lower than in the vehicle+DMM group. In addition, the level of expression of inflammatory factors in the capsaicin+DMM group was significantly higher than in the vehicle+DMM group. CONCLUSIONS: Capsaicin-induced sensory denervation accelerated OA progression at early stage in mice. To put it another way, sensory nerve protects from OA progression at early stage in mice.

Local Tensile Stress in the Development of Posttraumatic Osteoarthritis.

The pathogenesis of posttraumatic osteoarthritis (PTOA) remains unrevealed. We speculate that cartilage crack caused by joint trauma will induce local abnormal tensile stress, leading to change in extracellular matrix (ECM) expression of chondrocytes, cartilage degeneration, and initiation of osteoarthritis. Finite element model was used to examine whether the local tensile stress could be produced around the crack. Cell experiments were conducted to test the effect of tensile strain on chondrocyte ECM expression. Animal tests in rabbits were carried out to examine the change around the cartilage crack. The results indicated that the local tensile stress was generated around the crack and varied with the crack angles. The maximum principal tensile stress was 0.59 MPa around the 45° crack, and no tensile stress was found at 90°. 10% tensile strain could significantly promote type I collagen mRNA expression and inhibit type II collagen and aggrecan (the proteoglycan core protein) mRNA expression. Type I collagen was detected around the 45° crack region in the cartilage with no change in type II collagen and proteoglycan. We conclude that the local tensile stress produced around the cartilage crack can cause the change in cartilage matrix expression which might lead to cartilage degeneration and initiation of osteoarthritis. This study provides biomechanical-based insight into the pathogenesis of PTOA and potentially new intervention in prevention and treatment of PTOA.

Excessive tensile strain induced the change in chondrocyte phenotype.

PURPOSE: Chondrocyte extracellular matrix type II collagen and proteoglycans ensure an important compression-bearing structure in synovial joint. However, much more type I collagen is generated in osteoarthritis, which implies the presence of abnormal tensile strain in cartilage. We hypothesize that tensile stress influences chondrocyte phenotype at the cellular level, leading to potential osteoarthritis. METHODS: Chondrocytes were stimulated with cyclic excessive tensile (10%) or mild tensile or compressive strain (5%) at 0.5 Hz, 3 h per day for 3 days. Chondrocyte morphology and matrix proteoglycans level was separately determined by Rhodamine phalloidin and toluidine blue staining. The expression of cartilage marker molecules was measured using quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assays. RESULTS: Chondrocytes demonstrated significant fibroblastic morphology, reduced proliferation and increased apoptosis following exposure to 10% tensile strain. The 10% tensile strain group induced the lowest matrix proteoglycans level. It observably reduced the expression of COL2A1, Acan and SOX9, and increased COL1A1 expression level. The 5% tensile (5% compression) group, maintained the chondrocyte phenotype. CONCLUSIONS: The findings identified the effects of different magnitudes of tensile stress on chondrocyte phenotype compared to compressive strain. Further studies on cartilage biomechanical micro-environment might benefit from this study.

Mechanical stretch induces antioxidant responses and osteogenic differentiation in human mesenchymal stem cells through activation of the AMPK-SIRT1 signaling pathway.

Mesenchymal stem cells (MSCs) are promising cell sources for regenerative medicine. Growing evidence has indicated that mechanical stimuli are crucial for their lineage-specific differentiation. However, the effect of mechanical loading on redox balance and the intracellular antioxidant system in MSCs was unknown. In this study, human bone marrow-derived MSCs (BM-MSCs) were subjected to cyclic stretch at the magnitude of 2.5%, 5%, and 10%. Cell proliferation, intracellular reactive oxygen species (ROS), expression of antioxidant enzymes, and osteogenic differentiation were evaluated. RNA was extracted and subjected to DNA microarray analysis. Sirtinol and compound C were used to investigate the underlying mechanisms involved silent information regulator type 1 (SIRT1) and AMP-activated protein kinase (AMPK). Our results showed that mechanical stretch at appropriate magnitudes increased cell proliferation, up-regulated extracellular matrix organization, and down-regulated matrix disassembly. After 3 days of stretch, intracellular ROS in BM-MSCs were decreased but the levels of antioxidant enzymes, especially superoxide dismutase 1 (SOD1), were up-regulated. Osteogenesis was improved by 5% stretch rather than 10% stretch, as evidenced by increased matrix mineralization and osteogenic marker gene expression. The expression of SIRT1 and phosphorylation of AMPK were enhanced by mechanical stretch; however, inhibition of SIRT1 or AMPK abrogated the stretch-induced antioxidant effect on BM-MSCs and inhibited the stretch-mediated osteogenic differentiation. Our findings reveal that mechanical stretch induced antioxidant responses, attenuated intracellular ROS, and improved osteogenesis of BM-MSCs. The stretch-induced antioxidant effect was through activation of the AMPK-SIRT1 signaling pathway. Our findings demonstrated that appropriate mechanical stimulation can improve MSC antioxidant functions and benefit bone regeneration.

Is Preventative Long-Segment Surgery for Multi-Level Spondylolysis Necessary? A Finite Element Analysis Study.

OBJECTIVE: For multi-level spondylolysis patients, surgeons commonly choose to fix all the segments with pars interarticularis defect even those without slippage and not responsible for clinical symptoms. In this study, we tried to study the necessity of the preventative long-segment surgery for the defected segment without slippage in treatment of multi-level spondylolysis patients from a biomechanical perspective. METHOD: We established a bi-level spondylolysis model with pars defects at L4 and L5 segments, and simulated posterior lumbar interbody fusion (PLIF) and pedicle screw fixation at L5-S1 level. Then we compared the biomechanical changes at L4 segment before and after surgery in neutral, flexion, extension, lateral bending and axial rotation position. RESULTS: The stress on L4 pars interarticularis was very similar before and after surgery, and reached the highest in axial rotation. The L3-L4 intradiscal pressure was almost the same, while L4-L5 intradiscal pressure changed a little in lateral bending (increase from 1.993 to 2.160 MPa) and axial rotation (decrease from 1.639 to 1.307 MPa) after surgery. The PLIF surgery caused a little increase of range of motion at adjacent L4-L5 and L3-L4 levels, but the change is very tiny (1 degree). CONCLUSION: The PLIF surgery will not cause significant biomechanical change at adjacent segment with pars defect in multi-level spondylolysis. On the contrary, excessive long-segment surgery will damage surrounding soft tissues which are important for maintaining the stability of spine. So a preventative long-segment surgery is not necessary for multi-level spondylolysis as long as there are no soft tissue degeneration signs at adjacent level.

A functional variant in miR-143 promoter contributes to prostate cancer risk.

MicroRNAs are important regulators in numerous cellular processes, including cell differentiation, proliferation, and apoptosis. Recently, miR-143 was identified as a tumor suppressor in prostate cancer (PCa). To explore the mechanism of dysregulation and anti-tumor function of miR-143 in PCa, we first found a single-nucleotide polymorphism rs4705342T>C in the promoter region of miR-143 through bioinformatics tools and then performed a case-control study including 608 PCa patients and 709 controls. Results suggested that subjects with TC/CC genotypes had significantly decreased risk of PCa compared with those with TT genotype (adjusted OR 0.68, 95 % CI 0.55-0.85). Further functional assays showed that the risk-associated T allele increased the protein-binding affinity and reduced the activity of the promoter compared with C allele. In addition, restoration of miR-143 by mimics in PCa cells significantly inhibited cell proliferation and migration and down-regulated the expression level of kallikrein-related peptidase 2 (KLK2) mRNA and protein. The miR-143-KLK2 axis was also confirmed by luciferase reporter assay in vitro. In conclusion, our findings demonstrate that there is the significant association between the functional promoter variant rs4705342T>C in miR-143 and PCa risk and newly describe the miR-143-KLK2 interaction which provided another potential mechanism for miR-143 anti-tumor function.

Acoustic-frequency vibratory stimulation regulates the balance between osteogenesis and adipogenesis of human bone marrow-derived mesenchymal stem cells.

Osteoporosis can be associated with the disordered balance between osteogenesis and adipogenesis of bone marrow-derived mesenchymal stem cells (BM-MSCs). Although low-frequency mechanical vibration has been demonstrated to promote osteogenesis, little is known about the influence of acoustic-frequency vibratory stimulation (AFVS). BM-MSCs were subjected to AFVS at frequencies of 0, 30, 400, and 800 Hz and induced toward osteogenic or adipogenic-specific lineage. Extracellular matrix mineralization was determined by Alizarin Red S staining and lipid accumulation was assessed by Oil Red O staining. Transcript levels of osteogenic and adipogenic marker genes were evaluated by real-time reverse transcription-polymerase chain reaction. Cell proliferation of BM-MSCs was promoted following exposure to AFVS at 800 Hz. Vibration at 800 Hz induced the highest level of calcium deposition and significantly increased mRNA expression of COL1A1, ALP, RUNX2, and SPP1. The 800 Hz group downregulated lipid accumulation and levels of adipogenic genes, including FABP4, CEBPA, PPARG, and LEP, while vibration at 30 Hz supported adipogenesis. BM-MSCs showed a frequency-dependent response to acoustic vibration. AFVS at 800 Hz was the most favorable for osteogenic differentiation and simultaneously suppressed adipogenesis. Thus, acoustic vibration could potentially become a novel means to prevent and treat osteoporosis.

Identification of novel piRNAs in bladder cancer.

PIWI-interacting RNAs (piRNAs) are a newly identified class of small non-coding RNAs that can play important roles in germline development and carcinogenesis. In this study, piRNA microarrays were used to investigate global piRNA expression in three bladder cancer tissues and their adjacent normal tissues. Using the 3' untranslated region (UTR) sequence complementarily method, we predicted the target gene of piRNA. Our results showed that the expression levels of 106 piRNAs were up-regulated and 91 were down-regulated in bladder cancer tissues, among which the fold-change of down-regulated piRNA DQ594040 associated with bladder cancer (piRABC) was the highest piRNA. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to confirm piRABC expression in paired bladder cancer tissues and their adjacent normal tissues (n = 25). Over-expression of piRABC can inhibit bladder cancer cell proliferation, colony formation, and promote cell apoptosis (all P < 0.05). Luciferase reporter gene assays indicated that piRABC could increase the luciferase activity of TNFSF4. Western blotting analyses and ELISA assays also confirmed that the expression of TNFSF4 protein was up-regulated in control subjects compared with bladder cancer subjects. In conclusion, piRABC plays a crucial role in the development of bladder cancer.

Genetic variation in DROSHA 3'UTR regulated by hsa-miR-27b is associated with bladder cancer risk.

PURPOSE: miRNAs can regulate the biological processes, including differentiation, proliferation and apoptosis. DICER and DROSHA are two members of RNase III family, playing pivotal roles in the pathway of miRNAs biogenesis. In this study, we hypothesized that genetic variations of the DICER and DROSHA genes were associated with the bladder cancer risk. EXPERIMENTAL DESIGN: We performed a case-control study of 685 bladder cancer cases and 730 controls to investigate the association between the seven functional SNPs of DICER and DROSHA genes and bladder cancer risk. We then evaluated the functionality of the important SNPs. RESULTS: We found that rs10719T>C polymorphism located in 3' untranslated region (UTR) of DROSHA gene was associated with the increased risk of bladder cancer. Stratified analysis suggested that rs10719TC/CC genotype can increase risk of bladder cancer among male patients (Adjusted OR = 1.34, 95% CI = 1.05-1.70, P = 0.018), and ever smokers (1.56, 1.14-2.14, 0.006), compared with TT genotype. Furthermore, DROSHA rs10719T>C polymorphism was predicted to regulate the binding activity of hsa-miR-27a/b. Luciferase reported gene assay confirmed that rs10719 T to G substitution disrupted the binding site for hsa-miR-27b, resulting the increased levels of DROSHA protein. CONCLUSIONS: Taken together, these findings suggested that DROSHA rs10719T>C polymorphism may be associated with bladder cancer risk in a Chinese population, and hsa-miR-27b can influence the expression of DROSHA protein by binding with 3'UTR.

AdipoQ polymorphisms are associated with type 2 diabetes mellitus: a meta-analysis study.

OBJECTIVE: Adiponectin (AdipoQ) plays an important role in the pathogenesis of diabetes mellitus and is considered as an important candidate gene for type 2 diabetes mellitus (T2DM). So far, there have been many studies to investigate the association between the adiponectin polymorphisms and T2DM risk. However, the results are conflicting. To derive a more precise estimation, we performed a meta-analysis to assess the association between five AdipoQ polymorphisms [-11426A > G (rs16861194), -11391G > A (rs17300539), -11377C > G (rs266729), +45T > G (rs2241766) and +276G > T (rs1501299)], and T2DM risk. METHODS: The fixed and random-effects model should be used to assess the summary odds ratios (ORs) of each study. ORs with 95% confidence intervals (CIs) were used to evaluate the strength of association. On the basis of the included criteria, we selected 39 papers, among which eight for -11426A > G, 14 for -11391G > A, 21 for -11377C > G, 28 for +45 T > G and 24 for +276G > T. Sensitivity analyses were conducted to assess the stability of the results. Both Begg's funnel plots and Egger's test are commonly used to evaluate publication bias. RESULTS: Overall, we found that individuals with the -11426G allele had a 0.15-fold significantly increased T2DM risk (additive model: 1.15, 1.04-1.27, 0.222). In the stratified analyses, we found that the -11426A > G, -11391G > A and -11377C > G polymorphisms could increase T2DM risk in European populations in the additive model. For Asian populations, we found that the -11377C > G polymorphism also could elevate T2DM risk. CONCLUSIONS: Our results suggested that the adiponectin -11426A > G polymorphism could contribute to the T2DM risk.

EGFR 3'UTR 774T>C polymorphism contributes to bladder cancer risk.

Much evidence show that over-expression of epidermal growth factor receptor (EGFR) plays an important role in regulating carcinogenesis. Genetic variations in 3' untranslated region (3'UTR) of gene have been reported to affect gene expression by interfering with microRNAs (miRNAs), which are thought to function as either tumour suppressors or oncogenes by binding to their target mRNA. In this study, we investigated the association between the EGFR 3'UTR 774T>C polymorphism and bladder cancer risk. We used the TaqMan technology to genotype this genetic variant in a hospital-based case-control study of 908 bladder cancer patients and 1239 controls in a Chinese population. We found that the 774CC genotype was associated with a statistically significantly increased risk of bladder cancer [adjusted odds ratio = 1.29, 95% confidence interval = 1.05-1.58], compared with the 774TT/TC genotype, and this increased risk was more pronounced among subgroups of age > 65 years, non-smokers and patients' tumour invasive stage. Furthermore, luciferase assays in T24 cell showed that EGFR 3'UTR 774 T to C substitution could increase the expression of EGFR, which was consistent with the association study finding. Additionally, we also provide evidence that 774T>C polymorphism increasing EGFR expression was not regulated by hsa-miR-214 binding. These findings suggested that EGFR 3'UTR 774T>C polymorphism may contribute to susceptibility to bladder cancer.

A genetic variant in pre-miR-27a is associated with a reduced renal cell cancer risk in a Chinese population.

BACKGROUND: MicroRNAs (miRNAs) are a class of small non-coding RNAs to regulate cell differentiation, proliferation, development, and apoptosis. The single nucleotide polymorphism (SNP) rs895819 is located at the terminal loop of pre-miR-27a. Here, we aimed to investigate whether SNP rs895819 was associated with the development of renal cell cancer (RCC) in a Chinese population. METHODS: In this case-control study, we recruited 594 RCC patients and 600 cancer-free controls with frequency matched by age and sex. We genotyped this polymorphism using the TaqMan assay and assessed the effect of this polymorphism on RCC survival. Logistic regression model was used to assess the genetic effects on the development of RCC and interactions between rs895819 polymorphism and risk factors. RESULTS: Compared with AA homozygote, individuals carrying AG/GG genotypes had a statistically significant reduced susceptibility to RCC (adjusted OR = 0.71, 95% CI = 0.56-0.90). Furthermore, AG/GG genotypes were associated with reduced RCC susceptibility in localized clinical stage (adjusted OR = 0.71, 95% CI = 0.55-0.91), and similar effects were observed in well differentiated and poorly differentiated RCC (adjusted OR = 0.71, 95% CI = 0.55-0.93 for well differentiated, adjusted OR = 0.51, 95% CI = 0.28-0.93 for poorly differentiated). We also observed that rs895819 had multiplicative interactions with age and hypertension. However, the polymorphism did not influence the survival of RCC. CONCLUSION: Our results suggest that the pre-miR-27a rs895819 polymorphism can predict RCC risk in a Chinese population. Larger population-based prospective studies should be used to validate our findings.

Genetic variants in miRNAs predict bladder cancer risk and recurrence.

miRNAs play important roles in numerous cellular processes, including development, proliferation, apoptosis, and carcinogenesis. Because altered expression and function of miRNAs has been observed in bladder cancer, we investigated whether genetic variations in miRNAs are associated with bladder cancer risk and prognosis. Using bioinformatics tools, we selected five single-nucleotide polymorphisms located in miRNAs and used these to evaluate miRNA-disease associations in a two-stage model, consisting of 1,019 bladder cancer cases and 1,182 controls (683 cases and 728 controls in the training set and 336 cases and 454 controls in the test set). We found that miR-146a rs2910164 C allele was associated with significantly decreased risk of bladder cancer in both the training and test sets, as well as the combined set [OR = 0.80, 95% confidence interval (CI) = 0.71-0.90, P = 2.92 × 10(-4)]. Furthermore, the rs2910164 GC/CC genotypes conferred a significantly reduced risk of recurrence, compared with the GG genotype (P = 0.016). Functional analysis revealed that miR-146a rs2910164 C allele inhibited cell proliferation and significantly downregulated expression of IRAK1 and TRAF6 in bladder cancer cells. Additional examination of 64 bladder cancer tissues showed that individuals carrying the C allele had increased expression levels of miR-146a compared with those carrying the G allele (P = 0.010). Taken together, our findings show that miR-146a rs2910164 plays an important role in the risk and recurrence of bladder cancer, suggesting it may represent a biomarker for risk prevention and therapeutic intervention. Further larger and prospective cohorts are needed to validate our findings.

ADH1C Ile350Val polymorphism and cancer risk: evidence from 35 case-control studies.

BACKGROUND: Alcohol dehydrogenase 1C (ADH1C) is the key enzyme catalyze oxidation of alcohol to acetaldehyde, which plays vital roles in the etiology of various cancer. To date, studies investigated the association between a functional polymorphism in ADH1C, Ile350Val (rs698), and risk of cancer have shown inclusive results. METHODS: A meta-analysis based on 35 case-control studies was performed to address this issue. Odds ratios (OR) with 95% confidence intervals (CIs) were used to assess the association. The statistical heterogeneity across studies was examined with χ2-based Q-test. RESULTS: Overall, no significant associations between ADH1C Ile350Val polymorphism and cancer risk were observed in any genetic models (P>0.05). In the stratified analyses, there was a significantly increased cancer risk among African (Val/Val vs. Ile/Ile OR  =  2.19, 95% CI  =  1.29-3.73, P(heterogeneity)  =  0.989; Ile/Val + Val/Val vs. Ile/Ile: OR  =  1.79, 95%CI  =  1.18-2.71, P(heterogeneity)  =  0.761; Val/Val vs. Ile/Val + Ile/Ile: OR  =  1.92, 95% CI  =  1.16-3.17, P(heterogeneity)  =  0.981) and Asian (Ile/Val vs. Ile/Ile: OR  =  1.58, 95% CI  =  1.32-1.90, P(heterogeneity)  =  0.375; Val/Val vs. Ile/Ile: OR  =  3.84, 95% CI  =  1.74-8.49, P(heterogeneity)  =  0.160; Ile/Val + Val/Val vs. Ile/Ile: OR  =  1.65, 95% CI  =  1.38-1.96, P(heterogeneity)  =  0.330; Val/Val vs. Ile/Val + Ile/Ile: OR  =  3.54, 95% CI  =  1.62-7.75, P(heterogeneity)  =  0.154) studies. CONCLUSIONS: The results indicate that ADH1C Ile350Val polymorphism may contribute to cancer risk among Africans and Asians. Additional comprehensive system analyses are required to validate this association combined with other related polymorphisms.

The PSCA polymorphisms derived from genome-wide association study are associated with risk of gastric cancer: a meta-analysis.

PURPOSE: Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol-anchored 123-aa protein related to the cell-proliferation inhibition and/or cell-death induction activity. Many studies had reported the role of PSCA rs2294008 C > T and rs2976392 G > A polymorphisms on gastric cancer risk. METHODS: To investigate a more precise estimation of the relationships, we performed a meta-analysis on 9 case-control studies included 10,746 cases and 9,158 controls. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. RESULTS: For PSCA rs2294008 C > T polymorphism, there was a significantly increased risk of gastric cancer in all genetic models (TT/TC vs. CC: OR = 1.61, 95 % CI = 1.35-1.91; TT vs. TC/CC: OR = 1.33, 95 % CI = 1.24-1.42). Similar results were also observed for PSCA rs2976392 G > A polymorphism (AA/AG vs. GG: OR = 1.69, 95 % CI = 1.24-2.31; AA vs. AG/GG: OR = 1.36, 95 % CI = 1.24-1.50). In the stratified analysis by ethnicity of rs2294008, an increased gastric cancer risk was found in both Asians (TT vs. TC/CC: OR = 1.31, 95 % CI = 1.22-1.42) and Europeans (TT/TC vs. CC: OR = 1.42, 95 % CI = 1.18-1.71). Furthermore, when stratified by clinicopathologic characteristics of tumor location and histology, a higher risk on non-cardia compared with cardia gastric cancer (TT vs. TC/CC: OR = 1.43, 95 % CI = 1.12-1.83) as same as diffused compared with intestinal gastric cancer (TT vs. TC/CC: OR = 1.29, 95 % CI = 1.13-1.49) was observed. CONCLUSION: These findings supported that PSCA rs2294008 C > T and rs2976392 G > A polymorphisms may contribute to the susceptibility to gastric cancer, particular in non-cardia or diffused gastric cancer.

hOGG1 Ser326Cys polymorphism is associated with risk of bladder cancer in a Chinese population: a case-control study.

Human oxoguanine glycosylase 1 (hOGG1) is a DNA repair enzyme, which plays important roles in the base excision repair (BER) pathway. Several studies reported a common polymorphism Ser326Cys (rs1052133) in hOGG1, which conferred the susceptibility of bladder cancer. We hypothesized that the polymorphism is associated with risk of bladder cancer in a Chinese population. In a case-control study of 1050 histologically confirmed bladder cancer patients and 1404 age and sex matched healthy controls, we genotyped the hOGG1 Ser326Cys polymorphism using TaqMan technology and assessed its association with bladder cancer risk. We found that the hOGG1 Ser/Cys + Ser/Ser genotypes were associated with a significantly increased risk of bladder cancer (adjusted odds ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01-1.41), compared with the Cys/Cys genotype. Furthermore, the increased risk was more pronounced among subjects over age 65 years (OR = 1.31, 95% CI = 1.04-1.66), male subjects (OR = 1.21, 95% CI = 1.00-1.47), ever smokers (OR = 1.29, 95% CI = 1.00-1.68) and heavy smokers (>20 pack-years) (OR = 1.45, 95% CI = 1.03-2.04). No significant association was observed in the stratification of tumor grade and tumor stage for bladder cancer. In conclusion, our results suggest that hOGG1 Ser326Cys polymorphism may contribute to the susceptibility to bladder cancer in a Chinese population.

A functional polymorphism in miRNA-196a2 is associated with colorectal cancer risk in a Chinese population.

Single-nucleotide polymorphisms in microRNAs (miRNAs) may alter miRNA expression levels or processing and, thus, may contribute to cancer development. We hypothesized that miRNA-196a2 polymorphism is associated with risk of colorectal cancer (CRC). In a case-control study of 573 patients with CRC and 588 cancer-free controls frequency matched by age and sex, we genotyped the functional polymorphism rs11614913 (T>C) and assessed its association with the risk of CRC in a Chinese population. We found that the CT/CC genotypes were associated with a significantly increased risk of CRC (odds ratio [OR]=1.44, 95% confidence interval [CI]=1.10-1.88), compared with the TT genotype. Further, the polymorphism was significantly associated with the risk of patients with advanced stage tumor (Dukes C and D) (OR=1.65, 95% CI=1.11-2.46). Our results suggest that the functional polymorphism rs11614913 in miRNA-196a2 is involved in the etiology of CRC and, thus, may be a marker for genetic susceptibility to CRC.