Antihypertensive treatment during pregnancy induces long-term changes in gut microbiota and the behaviors of the attention deficit hyperactivity disorder offspring.

The pathogenesis of attention-deficit/hyperactivity disorder (ADHD) has not been fully elucidated. Gestational hypertension could double the probability of ADHD in the offspring, while the initial bacterial communication between the mother and offspring has been associated with psychiatric disorders. Thus, we hypothesize that antihypertensive treatment during pregnancy may abate the impairments in neurodevelopment of the offspring. To test this hypothesis, we chose Captopril and Labetalol, to apply to pregnant spontaneously hypertensive rat (SHR) dams and examined the outcomes in the male offspring. Our data demonstrated that maternal treatment with Captopril and Labetalol had long-lasting changes in gut microbiota and behavioral alterations, including decreased hyperactivity and increased curiosity, spatial learning and memory in the male offspring. Increased diversity and composition were identified, and some ADHD related bacteria were found to have the same change in the gut microbiota of both the dam and offspring after the treatments. LC-MS/MS and immunohistochemistry assays suggested elevated expression of brain derived neurotrophic factor (BDNF) and dopamine in the prefrontal cortex and striatum of offspring exposed to Captopril/ Labetalol, which may account for the improvement of the offspring's psychiatric functions. Therefore, our results support the beneficial long-term effects of the intervention of gestational hypertension in the prevention of ADHD.

Faecalibacterium prausnitzii Attenuates CKD via Butyrate-Renal GPR43 Axis.

BACKGROUND: Despite available clinical management strategies, chronic kidney disease (CKD) is associated with severe morbidity and mortality worldwide, which beckons new solutions. Host-microbial interactions with a depletion of Faecalibacterium prausnitzii in CKD are reported. However, the mechanisms about if and how F prausnitzii can be used as a probiotic to treat CKD remains unknown. METHODS: We evaluated the microbial compositions in 2 independent CKD populations for any potential probiotic. Next, we investigated if supplementation of such probiotic in a mouse CKD model can restore gut-renal homeostasis as monitored by its effects on suppression on renal inflammation, improvement in gut permeability and renal function. Last, we investigated the molecular mechanisms underlying the probiotic-induced beneficial outcomes. RESULTS: We observed significant depletion of Faecalibacterium in the patients with CKD in both Western (n=283) and Eastern populations (n=75). Supplementation of F prausnitzii to CKD mice reduced renal dysfunction, renal inflammation, and lowered the serum levels of various uremic toxins. These are coupled with improved gut microbial ecology and intestinal integrity. Moreover, we demonstrated that the beneficial effects in kidney induced by F prausnitzii-derived butyrate were through the GPR (G protein-coupled receptor)-43. CONCLUSIONS: Using a mouse CKD model, we uncovered a novel beneficial role of F prausnitzii in the restoration of renal function in CKD, which is, at least in part, attributed to the butyrate-mediated GPR-43 signaling in the kidney. Our study provides the necessary foundation to harness the therapeutic potential of F prausnitzii for ameliorating CKD.

Curcumin ameliorates hypertension via gut-brain communication in spontaneously hypertensive rat.

Gut dysbiosis and dysregulation of gut-brain communication have been identified in hypertensive patients and animal models. Previous studies have shown that probiotic or prebiotic treatments exert positive effects on the pathophysiology of hypertension. This study aimed to examine the hypothesis that the microbiota-gut-brain axis is involved in the antihypertensive effects of curcumin, a potential prebiotic obtained from Curcuma longa. Male 8- to 10-week-old spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) rats were divided into four groups: WKY rats and SHRs treated with vehicle and SHRs treated with curcumin in dosage of 100 or 300 mg/kg/day for 12 weeks. Our results show that the elevated blood pressure of SHRs was markedly decreased in both curcumin-treated groups. Curcumin treatment also altered the gut microbial composition and improved intestinal pathology and integrity. These factors were associated with reduced neuroinflammation and oxidative stress in the hypothalamus paraventricular nucleus (PVN). Moreover, curcumin treatment increased butyrate levels in the plasma, which may be the result of increased butyrate-producing gut microorganisms. In addition, curcumin treatment also activated G protein-coupled receptor 43 (GPR 43) in the PVN. These results indicate that curcumin reshapes the composition of the gut microbiota and ameliorates the dysregulation of the gut-brain communication to induce antihypertensive effects.

Expression patterns and prognostic value of RUNX genes in kidney cancer.

Kidney cancer is the third most common malignancy of the urinary system, of which, kidney renal clear cell carcinoma (KIRC) accounts for the vast majority. Runt-related transcription factors (RUNX) are involved in multiple cellular functions. However, the diverse expression patterns and prognostic values of RUNX genes in kidney cancer remained to be elucidated. In our study, we mined the DNA methylation, transcriptional and survival data of RUNX genes in patients with different kinds of kidney cancer through Oncomine, Gene Expression Profiling Interactive Analysis, UALCAN, Kaplan-Meier Plotter, cBioPortal and LinkedOmics. We found that RUNX1 and RUNX3 were upregulated in KIRC tissues compared with those in normal tissues. The survival analysis results indicated a high transcription level of RUNX1 was associated with poor overall survival (OS) in KIRC patients. Furthermore, KIRC tumor tissues had significantly lower levels of RUNX1 promoter methylation than that in paracancerous tissues, with decreased DNA methylation of RUNX1 notably associated with poor OS in KIRC. In conclusion, our results revealed that RUNX1 may be a potential therapeutic target for treating KIRC, and RUNX1 promoter methylation level shows promise as a novel diagnostic and prognostic biomarker, which laid a foundation for further study.

Specific ACE2 expression in small intestinal enterocytes may cause gastrointestinal symptoms and injury after 2019-nCoV infection.

The coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China and rapidly spread in other countries in December 2019. The infected patients presented with fever, respiratory symptoms, sometimes with digestive and other systemic manifestations, and some progressed with a severe acute respiratory syndrome or even death. Associated digestive symptoms were frequently observed in the patients, with an unknown significance and mechanism. ACE2, as the major known functional receptor of the 2019 novel coronavirus (2019-nCoV) attracted our attention. We collected the clinical data of the 2019-nCoV-infected patients from published studies and extracted the data about the incidence of gastrointestinal symptoms. Furthermore, we used online datasets to analyze ACE2 expression in different human organs, especially in the small intestine, to explore the relationship between ACE2 expression patterns and clinical symptoms. We found that diarrhea accounted for a notable proportion of COVID-19 patients, ranging from 8.0% to 12.9%. The results reveal that ACE2 mRNA and protein are highly expressed in the small intestinal enterocytes but not in the goblet cells or intestinal immune cells. High expression of ACE2 on the surface cells in the digestive tract may lead to gastrointestinal symptoms and inflammation susceptibility. Overall, digestive symptoms were common in the COVID-19 patients. ACE2 expression on surface cells of the small intestine may mediate the invasion and amplification of the virus and activation of gastrointestinal inflammation. It is a possible mechanism of digestive symptoms in the COVID-19 patients and explains the presence of the virus in patients' stool samples. The study also highlights the necessity of taking stool samples for suspected patients to help in early diagnosis and assessment of disease status.

The role of microRNA-608 polymorphism on the susceptibility and survival of cancer: a meta-analysis.

The role of rs4919510 polymorphism in microRNA-608 (miR-608) and cancer susceptibility and prognosis remain controversial and debatable. We conducted a meta-analysis of twenty-four eligible publications on the association of rs4919510 polymorphism with cancer risk and/or prognosis. Odds ratios, hazard ratios, and 95% confidence interval were used to investigate the association between this polymorphism and susceptibility, overall survival, and recurrence-free survival of cancer. Overall, eighteen case-control studies and nine cohort studies evaluated the susceptibility and prognostic value of rs4919510 polymorphism in cancer, respectively. Pooled analysis showed that rs4919510 polymorphism was not associated with cancer risk in all five genetic models. When stratifying by different cancer sites, rs4919510 polymorphism was detected to have a significant association with a decreased risk of colorectal cancer in homozygous model (P = 0.006) and recessive model (P = 0.001), subgroup analysis also emerged a weakened correlation between rs4919510 polymorphism and an increased risk of papillary thyroid cancer in heterozygote model (P = 0.04). Furthermore, the prognosis of rs4919510 variant in cancer patients showed that rs4919510 GG genotype was significant association with poor recurrence-free survival in homozygous models (P = 0.04). The meta-analysis suggested that the microRNA-608 rs4919510 polymorphism maybe associate with a significantly decreased risk for colorectal cancer. Further investigations on larger populations are required to evaluate and confirm this relationship.

Predictive Value of UGT1A1*28 Polymorphism In Irinotecan-based Chemotherapy.

The UGT1A1*28 polymorphism was suggested to be significantly connected with irinotecan-induced toxicity and response to chemotherapy. However, the results of previous studies are controversial. Hence we carried out a meta-analysis to investigate the effect of UGT1A1*28 polymorphism on severe diarrhea, neutropenia, and response of patients who had undergone irinotecan-based chemotherapy. The PubMed, Web of Science, Wanfang, and CNKI databases were searched for clinical trials assessing the association of UGT1A1*28 polymorphism with severe diarrhea, neutropenia, and response to irinotecan-based chemotherapy. The combined odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship under a fixed- or random-effects model. Fifty-eight studies including 6087 patients with cancer were included. Our results showed that patients carrying the TA6/7 and TA7/7 genotypes had a greater prevalence of diarrhea and neutropenia than those with the TA6/6 genotype (TA6/7+TA7/7 vs. TA6/6: diarrhea, OR = 2.18, 95%CI = 1.68-2.83; neutropenia, OR = 2.15, 95%CI = 1.71-2.70), particularly patients with metastatic colorectal cancer. Stratified analysis showed that Asians with the TA6/7 and TA7/7 genotypes were more likely to have diarrhea and neutropenia, and Caucasians with the TA6/7 and TA7/7 genotypes were more likely to have neutropenia than other groups. However, patients with the TA6/7+TA7/7 genotypes showed a higher response than patients with TA6/6 genotype (OR = 1.20, 95%CI = 1.07-1.34), particularly Caucasians (OR = 1.23, 95%CI = 1.06-1.42) and patients with metastatic colorectal cancer (OR = 1.24, 95%CI = 1.05-1.48). Our data showed that the UGT1A1*28 polymorphism had a significant relationship with toxicity and response to irinotecan-based chemotherapy. This polymorphism may be useful as a monitoring index for cancer patients receiving irinotecan-based chemotherapy.

MiR-146a and miR-196a-2 polymorphisms are associated with hepatitis virus-related hepatocellular cancer risk: a meta-analysis.

Previous studies have investigated the role of miR-146a rs2910164 and miR-196a-2 rs11614913 polymorphisms in hepatocellular carcinoma (HCC) susceptibility, but the results are contradictory and few specifically studied hepatitis virus-related HCC. Therefore, we conducted a meta-analysis to evaluate the association between these two polymorphisms and hepatitis virus-related HCC risk. We performed a systematical search in EMBASE, PubMed, Web of Science, CNKI and Wanfang databases as of 25th November, 2016. Finally, we assessed 14 studies involving 3852 cases and 5275 controls. Our results suggest that rs2910164 has a significant association with increased hepatitis virus-related HCC risk in allelic, homozygous, heterozygous, and dominant models (CG+GG vs. CC: OR=1.22, 95% CI=1.06-1.39, P=0.004), particularly in Chinese and HBV-related HCC subgroups. Conversely, rs11614913 was associated with lower hepatitis virus-related HCC risk in the overall analysis under allelic (T vs. C: OR=0.85, 95% CI=0.74-0.98, P=0.02), homozygous, dominant and recessive models. Subgroup analyses showed decreased risk in Chinese, HBV- and HCV-related HCC. In conclusion, miR-146a C>G (rs2910164) can increase HBV-related HCC risk while miR-196a-2 C>T (rs11614913) may decrease the risk of HBV- and HCV-related HCC, especially in the Chinese population. Further, large-scale studies including other races are required to confirm these findings.

Distinct role of the Fas rs1800682 and FasL rs763110 polymorphisms in determining the risk of breast cancer among Han Chinese females.

BACKGROUND: In recent years, studies have demonstrated that polymorphisms in the promoters of Fas and FasL are significantly associated with breast cancer risk. However, the results of these studies were inconsistent. This case-control study was performed to explore the associations between Fas rs1800682 and FasL rs763110 polymorphisms and breast cancer. MATERIALS AND METHODS: A hospital-based case-control study of 560 Han Chinese females with breast cancer (583 controls) was conducted. The MassARRAY system was used to search for a possible association between the disease risk and the two single nucleotide polymorphisms, Fas rs1800682 and FasL rs763110. Statistical analyses were performed using SNPStats software to conduct Pearson's chi-square tests in five different genetic models. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated after adjustment to age and body mass index. PHASE v2.1 software was used to reconstruct all common haplotypes. RESULTS: A statistically significant association was found between Fas rs1800682 and increased breast cancer risk (AG vs AA: OR =1.37, 95% CI =1.06-1.78; AA+AG vs GG: OR =1.32, 95% CI =1.04-1.66), and also it was found that the FasL rs763110 polymorphism may decrease the risk. Stratified analyses demonstrated that the rs763110 polymorphism was associated with lower breast cancer risk among postmenopausal females (heterozygote model: OR =0.69, 95% CI =0.49-0.97; dominant model: OR =0.70, 95% CI =0.51-0.96). The T allele of rs763110 was also associated with a decreased risk of lymph node metastasis (allele model: OR =0.75, 95% CI =0.57-0.97) and an increased risk of the breast cancer being human epidermal growth factor receptor 2 positive (allele model: OR =1.37, 95% CI =1.03-1.18). Moreover, haplotype analysis showed that Ars1800682Trs763110 was associated to a statistically significant degree with lower risk of breast cancer (OR =0.70, 95% CI =0.53-0.91). CONCLUSION: These data suggest that the presence of Fas rs1800683 is an important risk factor for breast cancer, whereas FasL rs763110 may exert a protective effect against the onset of breast cancer.

The Associations of Single Nucleotide Polymorphisms in miR196a2, miR-499, and miR-608 With Breast Cancer Susceptibility: A STROBE-Compliant Observational Study.

MicroRNAs (miRNAs) play an important role as regulators of tumor suppressors and oncogenes in cancer-related processes. Single nucleotide polymorphisms (SNPs) in miRNAs have been shown to be relevant to various different cancers, including breast cancer (BC). The aim of this study was to estimate the associations between miRNA-related gene polymorphisms (miR-196a2, miR-499, and miR-608) and the risk of BC in a Chinese population. Gene polymorphisms were analyzed in 1143 subjects (controls = 583; BC = 560). The 3 SNPs were genotyped using the Sequenom Mass-ARRAY platform. The associations between the SNP frequencies and BC were assessed by computing odds ratios (ORs) and 95% confidence intervals (95% CIs), as well as by applying Chi-square tests. The miR-196a2 (rs11614913) T allele was associated with a decreased risk of BC based on results from dominant (OR = 0.67, 95% CI = 0.52-0.86), recessive (OR = 0.65, 95% CI = 0.48-0.86), and allele models (OR = 0.73, 95% CI = 0.62-0.86). In contrast, the miR-499 (rs3746444) AG/GG genotypes were associated with an increased risk of BC (OR = 1.45, 95% CI = 1.10-1.91), and miR-608 (rs4919510) was not significantly associated with BC risk. Our study suggested that the polymorphisms of rs11614913 and rs3746444 may be associated with BC risk in Chinese individuals.

Role of IL-17A rs2275913 and IL-17F rs763780 polymorphisms in risk of cancer development: an updated meta-analysis.

Single nucleotide polymorphisms (SNPs) in the interleukin-17 (IL-17) gene have been shown to be correlated with susceptibility to cancer. However, various studies report different results of this association. The aim of the present work was to clarify the effects of IL-17A G197A (rs2275913) and IL-17F T7488C (rs763780) polymorphisms on cancer risk. We performed systematic searches of the PubMed and CNKI databases to obtain relevant publications. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the association of rs2275913 and rs763780 polymorphisms with cancer risk. Data were extracted from the selected studies, and statistical analysis was conducted using the STATA software. Our results indicated that rs2275913 and rs763780 polymorphisms significantly increase cancer risk, especially in gastric cancers. Subgroup analysis suggested the existence of a significant correlation between rs763780 polymorphism and cancer susceptibility in Caucasian populations. This updated meta-analysis confirms that rs2275913 and rs763780 polymorphisms are highly associated with increased risk for multiple forms of cancer.

Association Between Single Nucleotide Polymorphisms in DNA Polymerase Kappa Gene and Breast Cancer Risk in Chinese Han Population: A STROBE-Compliant Observational Study.

DNA polymerases are responsible for ensuring stability of the genome and avoiding genotoxicity caused by a variety of factors during DNA replication. Consequently, these proteins have been associated with an increased cancer risk. DNA polymerase kappa (POLK) is a specialized DNA polymerase involved in translesion DNA synthesis (TLS) that allows DNA synthesis over the damaged DNA. Recently, some studies investigated relationships between POLK polymorphisms and cancer risk, but the role of POLK genetic variants in breast cancer (BC) remains to be defined. In this study, we aimed to evaluate the effects of POLK polymorphisms on BC risk.We used the Sequenom MassARRAY method to genotype 3 single nucleotide polymorphisms (SNPs) in POLK (rs3213801, rs10077427, and rs5744533), in order to determine the genotypes of 560 BC patients and 583 controls. The association of genotypes and BC was assessed by computing the odds ratio (OR) and 95% confidence intervals (95% CIs) from logistic regression analyses.We found a statistically significant difference between patient and control groups in the POLK rs10077427 genotypic groups, excluding the recessive model. A positive correlation was also found between positive progesterone receptor (PR) status, higher Ki67 index, and rs10077427 polymorphism. For rs5744533 polymorphism, the codominant, dominant, and allele models frequencies were significantly higher in BC patients compared to healthy controls. Furthermore, our results indicated that rs5744533 SNP has a protective role in the postmenopausal women. However, we failed to find any associations between rs3213801 polymorphism and susceptibility to BC.Our results indicate that POLK polymorphisms may influence the risk of developing BC, and, because of this, may serve as a prognostic biomarker among Chinese women.

Association of IL-23R Polymorphisms (rs6682925, rs10889677, rs1884444) With Cancer Risk: A PRISMA-Compliant Meta-Analysis.

Although interleukin (IL)-23 receptor (IL-23R) plays an important role in the pathogenesis of multiple cancers, its association with cancer risk is inconsistent across different studies. We therefore conducted a meta-analysis with the aim of resolving the relationship among the 3 common polymorphisms of IL-23R (rs6682925, rs10889677, rs1884444) and cancer risk.Case-control studies evaluating the association between IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) and cancer risk were searched in the PubMed, Web of Science, and CNKI databases.Data were included in the meta-analysis if they were from original studies adopting a case-control design investigating the association between IL-23R polymorphisms and risk of any cancer; all cancer cases must have been confirmed by histology or pathology, and controls selected from noncancer individuals. Case-only studies and review papers were excluded.Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the relationship of IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) with cancer risk. A random-effects model or fixed-effects model was used depending on the heterogeneity of the data.Ultimately, 15 studies, involving 8784 cancer patients and 10,321 cancer-free controls, were included in our meta-analysis. In the overall analysis, the rs10889677 polymorphism was associated with breast cancer (BC) under the allelic, homozygous, dominant, and heterozygous models. Rs1884444 polymorphism was relevant to hepatocellular carcinoma (HCC) under the homozygous, recessive, and allelic models. However, no evidence of a relationship between IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) and cancer risk was found in the overall population.Our meta-analysis provides no evidence supporting a global association of IL-23R polymorphisms (rs6682925, rs10889677, rs1884444) with the risk of cancer. However, rs10889677 may be associated with BC susceptibility and rs1884444 had association with HCC risk. Further large and well-designed studies are warranted to confirm this finding.

Association of Vitamin D Receptor Cdx-2 Polymorphism With Cancer Risk: A Meta-Analysis.

Vitamin D receptor (VDR) Cdx-2 polymorphism (rs11568820) has been indicated to be associated to cancer susceptibility. However, published studies reported mixed results. This meta-analysis was conducted to get a more accurate estimation of the association between Cdx-2 polymorphism and cancer risk.We identified 25 independent studies with a total of 34,018 subjects published prior to March 2015. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to cancer. Separate analyses were conducted on features of the population such as ethnicity, source of controls, and cancer types.Meta-analysis results showed that Cdx-2 polymorphism significantly increased cancer risk in the homozygous model in overall analysis. According to the further stratified analysis, significant association was found between Cdx-2 variant and cancer risk in American-Africans in the homozygous, recessive, and dominant comparison models. However, no significant associations were found in Caucasians and Asians. When stratified by different cancer types, significant association was observed between Cdx-2 variant and an increased risk of colorectal cancer in the homozygous, recessive, and dominant models. In addition, ovarian cancer susceptibility increased based on the homozygous and dominant comparison models.Our study indicated that VDR Cdx-2 polymorphism was associated with an increased cancer risk, particularly in American-Africans, colorectal, and ovarian cancers. However, other factors may impact on the association. Further multicenter studies are needed to confirm the effects of Cdx-2 polymorphism on cancer susceptibility.

Current evidence on the relationship between two common polymorphisms in NPAS2 gene and cancer risk.

The relationship between neuronal PAS domain protein 2 (NPAS2) gene polymorphisms and cancer risk has been widely investigated. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation on the relationship. We searched Pubmed, and Web of Knowledge databases until Dec, 2014 to identify eligible studies. Case-control studies containing available genotype frequencies of the NPAS2 polymorphisms were chosen. The odds ratios (ORs) with 95% confidence interval (CI) were used to assess the strength of association. Eight independent case-control studies with 3,857 cancer patients and 4,525 cancer-free controls were selected for this meta-analysis. Two NPAS2 gene polymorphisms were identified (rs2305160 and rs17024926). The results showed statistically significant associations of rs2305160 with cancer risk (AA+GA vs. GG: OR = 0.84, 95% CI = 0.72-0.98, P = 0.02; AG vs. GG: OR = 0.81, 95% CI = 0.68-0.96, P = 0.02). Stratified analysis by cancer type indicated that rs2305160 may decrease the risk of breast cancer (A vs. G: OR = 0.87, 95% CI = 0.76-0.96, P = 0.006; AA+GA vs. GG: OR = 0.77, 95% CI = 0.67-0.88, P<0.001; AG vs. GG: OR = 0.74, 95% CI = 0.64-0.86, P<0.001), whereas negative results were obtained for prostate cancer. For rs17024926 polymorphism, there was no significant association in any genetic model. This meta-analysis suggests that NPAS2 rs2305160 polymorphism may reduce cancer susceptibility, especially in breast cancer.

Association between interleukin-10-3575T>A (rs1800890) polymorphism and cancer risk.

BACKGROUND: Previous studies investigated the associations of interleukin-10 (IL-10) polymorphisms with different types of cancer, indicating an influence on cancer risk. IL-10-3575T>A (rs1800890) has been studied concerning a potential implication in terms of some cancer site risks, but the results from single studies are contradictory. METHODS: Eligible articles were identified by a search of the PubMed, Web of Science, and Chinese National Knowledge Infrastructure (CNKI) databases until November 30, 2014. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the cancer risk by cancer sites, ethnicity, and other study features. RESULTS: We identified 15 published studies to research the link of the IL-10-3575T>A polymorphism with cancer risk. Our meta-analysis indicated that the IL-10-3575T>A polymorphism has a significant association with decreased melanoma risk in the heterozygote model (OR=0.67, 95% CI=0.49-0.92, p=0.02) and dominant model (OR=0.70, 95% CI=0.52-0.95, p=0.01), but increased diffuse large B-cell lymphoma (DLBCL) risk in all the different genetic models. CONCLUSION: Our analysis suggests that the IL-10-3575T>A mutation may associate with melanoma and DLBCL and exert a differential effect in different cancer sites. However, other factors may influence the association, and large-scale multicenter with adequate methodological quality studies are needed to confirm the impact on cancer susceptibility.

PSCA rs2294008 C > T polymorphism contributes to gastric and bladder cancer risk.

BACKGROUND: Previous studies suggested genetic variations in PSCA (prostate stem cell antigen) may confer the susceptibility of cancer. Many case-control studies have reported the relationship between PSCA rs2294008 C > T polymorphism and cancer, especially gastric cancer and bladder cancer. However, the results are inconsistent. This meta-analysis is aimed at evaluating the association of rs2294008 polymorphism with cancer risk. METHODS: The databases of PubMed, ISI Web of Knowledge, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) were searched for related publications. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Fixed models were used when heterogeneity among studies was not detected, otherwise the random model was used. RESULTS: Twenty-six studies from 24 articles with 30,050 multiple cancer cases and 51,670 controls were pooled into this meta-analysis. The results showed that the rs2294008 polymorphism was associated with increased cancer risk in any genetic model (T vs C, OR: 1.18, 95% CI: 1.08-1.28; TT vs CC, OR: 1.36, 95% CI: 1.14-1.62; TC vs CC, OR: 1.29, 95% CI: 1.17-1.44; TT + TC vs CC, OR: 1.32, 95% CI: 1.18-1.49; TT vs TC + CC, OR: 1.15, 95% CI: 1.02-1.30). In stratified analysis by cancer type, we found that the T allele had a significant high risk of gastric and bladder cancer, but not in other cancers. In subgroup analysis by ethnicity, increased cancer risk was found in both Asians and Caucasians. CONCLUSION: Our study suggested that the PSCA rs2294008 C > T polymorphism is a risk factor for cancer, especially in gastric and bladder cancer.

Association of the four common polymorphisms in interleukin-10 (rs1800890, rs1800896, rs1800871, and rs1800872) with non-Hodgkin's lymphoma risk: a meta-analysis.

Interleukin-10 (IL-10) single nucleotide polymorphisms (SNPs) have been indicated to be correlated with Non-Hodgkin's lymphoma (NHL) susceptibility. However, the results of these studies on the association remain inconsistent. This meta-analysis was conducted to derive a more accuracy estimation of the association between the common SNPs (rs1800890, rs1800896, rs1800871 and rs1800872) in IL-10 and NHL risk. Meta-analyses were performed on 21 studies with 7,749 cases and 8584 controls. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the NHL risk. Meta-analyses showed that rs1800890, rs1800871 and rs1800872 polymorphisms had no association with NHL risk. However, rs1800896 polymorphism has association with NHL risk based on the following comparison models (G vs. A: OR = 1.14, 95% CI = 1.00-1.29; AG vs. AA: OR = 1.20, 95% CI = 1.05-1.37; GG+AG vs. AA: OR = 1.22, 95% CI = 1.08-1.39). In the ethnic subgroup analysis, rs1800896 had an increased NHL risk in Caucasians based on the heterozygote model (OR = 1.21, 95% CI = 1.04-1.41) and dominant model (OR = 1.22, 95% CI = 1.00-1.48). When stratified by subtypes, rs1800890, rs1800896 and rs1800872 polymorphisms were found significant association with an increased risk of diffuse large B-cell Lymphoma (DLBCL) in different comparison models, whereas negative results were obtained for Follicular Lymphoma (FL) and chronic lymphocytic Leukemia/small lymphocytic Lymphoma (CLL/SLL) in all genetic models. Our meta-analysis suggested that the rs1800896 polymorphism had an increased risk with NHL susceptibility, where as the rs1800890, rs1800871 and rs1800872 had no association with NHL risk. Among the common subtypes of NHL, three polymorphisms (rs1800890, rs1800896 and rs1800872) had significant association with DLBCL risk.