Genome-wide DNA methylation analysis identifies potent CpG signature for temzolomide response in non-G-CIMP glioblastomas with unmethylated MGMT promoter: MGMT-dependent roles of GPR81.

PURPOSES: To identify potent DNA methylation candidates that could predict response to temozolomide (TMZ) in glioblastomas (GBMs) that do not have glioma-CpGs island methylator phenotype (G-CIMP) but have an unmethylated promoter of O-6-methylguanine-DNA methyltransferase (unMGMT). METHODS: The discovery-validation approach was planned incorporating a series of G-CIMP-/unMGMT GBM cohorts with DNA methylation microarray data and clinical information, to construct multi-CpG prediction models. Different bioinformatic and experimental analyses were performed for biological exploration. RESULTS: By analyzing discovery sets with radiotherapy (RT) plus TMZ versus RT alone, we identified a panel of 64 TMZ efficacy-related CpGs, from which a 10-CpG risk signature was further constructed. Both the 64-CpG panel and the 10-CpG risk signature were validated showing significant correlations with overall survival of G-CIMP-/unMGMT GBMs when treated with RT/TMZ, rather than RT alone. The 10-CpG risk signature was further observed for aiding TMZ choice by distinguishing differential outcomes to RT/TMZ versus RT within each risk subgroup. Functional studies on GPR81, the gene harboring one of the 10 CpGs, indicated its distinct impacts on TMZ resistance in GBM cells, which may be dependent on the status of MGMT expression. CONCLUSIONS: The 64 TMZ efficacy-related CpGs and in particular the 10-CpG risk signature may serve as promising predictive biomarker candidates for guiding optimal usage of TMZ in G-CIMP-/unMGMT GBMs.

Lineage-selective super enhancers mediate core regulatory circuitry during adipogenic and osteogenic differentiation of human mesenchymal stem cells.

Human mesenchymal stem cells (hMSCs) can be differentiated into osteoblasts and adipocytes. During these processes, super enhancers (SEs) play important roles. Here, we performed comprehensive characterization of the SEs changes associated with adipogenic and osteogenic differentiation of hMSCs, and revealed that SEs changed more dramatically compared with typical enhancers. We identified a set of lineage-selective SEs, whose target genes were enriched with cell type-specific functions. Functional experiments in lineage-selective SEs demonstrated their specific roles in directed differentiation of hMSCs. We also found that some key transcription factors regulated by lineage-selective SEs could form core regulatory circuitry (CRC) to regulate each other's expression and control the hMSCs fate determination. In addition, we found that GWAS SNPs of osteoporosis and obesity were significantly enriched in osteoblasts-selective SEs or adipocytes-selective SEs, respectively. Taken together, our studies unveiled important roles of lineage-selective SEs in hMSCs differentiation into osteoblasts and adipocytes.

Accidental venous port placement via the persistent left superior vena cava: Two case reports.

BACKGROUND: Breast cancer poses a great threat to females worldwide. There are various therapies available to cure this common disease, such as surgery, chemotherapy, radiotherapy, and immunotherapy. Implantable venous access ports (IVAP, referred to as PORT) have been widely used for breast cancer chemotherapy. Venous malformations are possible conditions encountered during PORT implantation. Persistent left superior vena cava (PLSVC) is a common superior vena cava malformation. Most patients have normal right superior vena cava without affecting hemodynamics, so patients often have no obvious symptoms. CASE SUMMARY: We incidentally found that two patients had PLSVC while a PORT was implanted via the internal jugular vein. Due to chemotherapy for breast cancer, PORT was successfully implanted under the guidance of ultrasound into these 2 patients. Positive chest X-ray examination after the operation showed that the catheter ran beside the left mediastinum and the end was located in the seventh thoracic vertebra. The patients had no catheter-related complications and successfully completed the course of chemotherapy. Ultrasonography found that the ratio of PORT outer diameter to PLSVC inner diameter was less than 0.45, which was in line with the recommendations of relevant literature and operating guidelines. The purpose of this article is to introduce two rare cases and review the relevant literature. CONCLUSION: Correct assessment of PLSVC status and ultrasound-guided PORT placement generally does not affect breast cancer patients chemotherapy.

Salidroside improved cerebrovascular vasodilation in streptozotocin-induced diabetic rats through restoring the function of BKCa channel in smooth muscle cells.

Vessel disease is a kind of severe complication in diabetic patients. However, few pharmacologic agents can directly recover diabetic vascular function. Salidroside (SAL), a major ingredient from Rhodiola rosea, has been found to have an obvious hypoglycemic effect and a beneficial protection on vascular function in diabetes. However, whether SAL is a suitable treatment for diabetes has not so far been evaluated and the underlying mechanisms remain unknown. The present work aims to (1) investigate the potential effects of SAL on cerebrovascular relaxation in streptozotocin-induced diabetic rats or when exposed to acute hyperglycemia condition and (2) examine whether function of the BKCa channel is involved in SAL treatment for diabetic vascular relaxation. Our results indicate that chronic administration of 100 mg/kg/day SAL not only improves cerebrovascular relaxation but also increases BKCa ß1-subunit expressions at both protein and mRNA levels and enhances BKCa whole-cell and single-channel activities in cerebral VSMCs of diabetic rats. Correspondingly, acute application of 100 µM SAL induces cerebrovascular relaxation by activation of the BKCa channel. Furthermore, SAL activated the BKCa channel mainly through acting on the ß1-subunit in HEK293 cells transfected with hSloα+ß1 constructs. We concluded that SAL improved vasodilation in diabetic rats through restoring the function of the BKCa-ß1 subunit in cerebrovascular smooth muscle cells, which may be the underlying mechanism responsible for the vascular protection of SAL in diabetes.

Genetic polymorphisms (rs10636 and rs28366003) in metallothionein 2A increase breast cancer risk in Chinese Han population.

Genetic polymorphisms of MT2A are frequently observed in many different cancers. We performed this case-control study, including 459 breast cancer (BC) patients and 549 healthy controls from Northwest China, to evaluate the associations between two common MT2A polymorphisms (rs10636 and rs28366003) and BC risk. The MT2A polymorphisms were genotyped via Sequenom MassARRAY. The individuals with the rs28366003 A/G, A/G-G/G genotypes underwent a higher risk of BC (P<0.0001). And, the minor allele G of rs28366003 was related to an increased BC risk (P<0.0001). We also found a significantly increased BC risk with rs10636 polymorphism among homozygote and recessive models (P<0.05). Further subgroup analysis by clinical characteristics of BC patients showed that Scarff, Bloom and Richardson tumor grade (SBR) 1-2 have a higher expression of the minor allele of these two MT2A loci than SBR 3. Our results indicated that the rs10636 and rs28366003 polymorphisms in MT2A increased BC risk in Northwest Chinese Han population.

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.

PD-1 rs2227982 Polymorphism Is Associated With the Decreased Risk of Breast Cancer in Northwest Chinese Women: A Hospital-Based Observational Study.

Programmed death-1 (PD-1) is crucial in cancer and is well characterized as a negative T-cell regulator that functions by delivering inhibitory signals. We aimed to evaluate the relationship between PD-1 polymorphisms (rs10204525, rs2227982, and rs7421861) and breast cancer risk.We selected 560 breast cancer patients and 583 age-, sex-, and ethnicity-matched healthy controls from Northwest China. The PD-1 polymorphisms were genotyped by using Sequenom MassARRAY. Associations were estimated with odds ratios (ORs) and 95% confidence intervals (95% CIs).For the rs10204525 and rs7421861 polymorphisms, no differences in breast cancer risk were found in any of the genetic models. For the rs2227982 polymorphism, the variant genotypes were significantly associated with decreased breast cancer risk (CT vs CC: OR = 0.68, 95% CI = 0.52-0.91; CT + TT vs CC: OR = 0.69, 95% CI = 0.53-0.90). In analyses stratified by age, the decreased risk was observed among the younger subjects (OR = 0.68, 95% CI = 0.47-0.97). We found that the decreased risk observed for the variant genotypes of rs2227982 was associated with the Her-2 status (CT vs CC: OR = 0.55, 95% CI = 0.37-0.84; CT + TT vs CC: OR = 0.56, 95% CI = 0.38-0.82). The haplotype analysis showed that the Ars10204525 Trs2227982 Crs7421861 haplotype was associated with a significantly decreased risk of breast cancer (OR = 0.50, 95% CI = 0.34-0.75).Our findings support an association between the PD-1 rs2227982 polymorphism and decreased breast cancer risk, especially in Her-2 positive breast cancer patients in the Chinese population.

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.

Genetic Variation in Metastasis-Associated in Colon Cancer-1 and the Risk of Breast Cancer Among the Chinese Han Population: A STROBE-Compliant Observational Study.

Metastasis-associated in colon cancer-1 (MACC1), a newly identified oncogene, is involved in angiogenesis, invasiveness, and metastasis in many cancers. Epidemiological studies have indicated the associations between MACC1 polymorphisms and cancer risk. However, the association between genetic polymorphisms in MACC1 and breast cancer (BC) was not clear. This study aimed to evaluate the relationship between MACC1 polymorphisms and BC risk.We genotyped 4 single-nucleotide polymorphisms (SNPs) in MACC1 (rs975263, rs1990172, rs3735615, rs4721888) to determine the haplotypes in 560 BC patients and 583 age-, sex-, and ethnicity-matched healthy individuals. Genotypes were determined using the Sequenom MassARRAY method. We estimated the odds ratios (ORs) and 95% confidence intervals (95% CIs) using the chi-square test.There were significant differences between patients and controls in the MACC1 rs975263 allelic (T vs C: OR = 0.76, 95% CI = 0.61-0.95, P = 0.014) and genotypic groups (TC vs TT: OR = 0.70, 95% CI = 0.54-0.92, P = 0.009; TC+CC vs TT: OR = 0.71, 95% CI = 0.55-0.92, P = 0.008). Analysis of clinical features demonstrated significant associations between rs975263 and Scarff-Bloom-Richardson (SBR) grade 3 cancer (P = 0.006) and postmenopausal women (P = 0.018). Compared with the rs4721888 CC genotype, the frequency of rs4721888 GC and GC+CC variants was higher in patients. Further analysis revealed that the variant genotypes were positively associated with lymph node metastasis. However, we failed to find any relationships between rs1990172 or rs3735615 polymorphism and BC risk. In addition, haplotype analysis indicated that the CTGG and CTCG haplotypes (rs975263, rs1990172, rs3735615, rs4721888) were significantly associated with decreased susceptibility to BC (P = 0.029 and 0.019 respectively).Our results suggest that rs975263 and rs4721888 polymorphisms in MACC1 are associated with the risk of BC susceptibility and may be involved in the progression of BC in Chinese women.

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.

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.

Quantitative Assessment of the Association between Genetic Variants in MicroRNAs and Colorectal Cancer Risk.

BACKGROUND: The associations between polymorphisms in microRNAs and the susceptibility of colorectal cancer (CRC) were inconsistent in previous studies. This study aims to quantify the strength of the correlation between the four common polymorphisms among microRNAs (hsa-mir-146a rs2910164, hsa-mir-149 rs2292832, hsa-mir-196a2 rs11614913, and hsa-mir-499 rs3746444) and CRC risk. METHODS: We searched PubMed, Web of Knowledge, and CNKI to find relevant studies. The combined odds ratio (OR) with 95% confidence interval (95% CI) was used to estimate the strength of the association in a fixed or random effect model. RESULTS: 15 studies involving 5,486 CRC patients and 7,184 controls were included. Meta-analyses showed that rs3746444 had association with CRC risk in Caucasians (OR = 0.57, 95% CI = 0.34-0.95). In the subgroup analysis, we found significant associations between rs2910164 and CRC in hospital based studies (OR = 1.24, 95% CI = 1.03-1.49). rs2292832 may be a high risk factor of CRC in population based studied (OR = 1.18, 95% CI = 1.08-1.38). CONCLUSION: This meta-analysis showed that rs2910164 and rs2292832 may increase the risk of CRC. However, rs11614913 polymorphism may reduce the risk of CRC. rs3746444 may have a decreased risk to CRC in Caucasians.

Effects of PSCA rs2294008 (C/T) and c-MYC rs9642880 (G/T) polymorphisms on bladder cancer: evidence from a meta-analysis.

Previous studies have investigated the associations between the two polymorphisms (prostate stem cell antigen (PSCA) rs2294008 C/T and c-MYC rs9642880 G/T) and bladder cancer (BC) risk. However, the results are inconsistent. We therefore carried out a meta-analysis to estimate the relationship between PSCA/c-MYC polymorphisms and BC risk. We searched PubMed up to November 2014 to identify potentially eligible literatures. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations, the data were further stratified by ethnicity. Heterogeneity was evaluated by Q test and I(2) statistics. Begg's funnel plot and Egger's test were used to assess the publication bias. 11 studies from 9 articles were identified, including a total of 16,814 cancer cases and 52,868 case-free controls. We found a significant association between PSCA rs2294008 polymorphism and BC risk (the allele contrast model: OR = 1.14, 95% CI = 1.11-1.18; homozygote comparison: OR = 1.28, 95% CI = 1.20-1.37; heterozygote comparison: OR = 1.23, 95% CI = 1.17-1.30; dominant model: OR = 1.25, 95% CI = 1.19-1.31 and recessive model: OR = 1.13, 95% CI = 1.07-1.20). Moreover, a significant increased risk of BC was confirmed both in Caucasian and in Asians. For c-MYC rs9642880 polymorphism, significant increased BC risk was detected under the following genetic models (the allele contrast model: OR = 1.20, 95% CI = 1.13-1.27; homozygote comparison: OR = 1.37, 95% CI = 1.21-1.55; heterozygote comparison: OR = 1.20, 95% CI = 1.09-1.32; dominant model: OR = 1.25, 95% CI = 1.14-1.37 and recessive model: OR = 1.26, 95% CI = 1.13-1.40). Further stratified analysis by ethnicity also observed the same results. This meta-analysis suggested that PSCA rs2294008 and c-MYC rs9642880 polymorphisms may increase the BC risk. Further studies are needed to clarify the effects.

Relationship between apurinic endonuclease 1 Asp148Glu polymorphism and gastrointestinal cancer risk: An updated meta-analysis.

AIM: To evaluate the relationship between apurinic endonuclease 1 (APE1) Asp148Glu polymorphism and the susceptibility to gastrointestinal (GI) cancers. METHODS: We searched PubMed, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases updated on July 15, 2014 for relevant studies. Only case-control studies comparing APE1 Asp148Glu polymorphism and GI cancer risk were included. We excluded studies reporting only standardized incidence ratios without control groups and those without detailed genotyping data. Meta-analysis was performed on 17 studies involving 4856 cancer patients and 6136 cancer-free controls. Review Manager version 5.1 was used to perform the meta-analysis. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated under the allele contrast, homozygous, heterozygous, dominant and recessive genetic models. We also conducted subgroup analyses stratified by ethnicity and cancer type. Publication bias was evaluated using Begg's test. RESULTS: The meta-analysis showed a significant association between APE1 Asp148Glu polymorphism and GI cancer risk in three genetic models in the overall population (G vs T: OR = 1.18; 95%CI: 1.05-1.32; TG vs TT: OR = 1.28; 95%CI: 1.08-1.52; TG + GG vs TT: OR = 1.32; 95%CI: 1.10-1.57). Stratified analysis by ethnicity revealed a statistically increased GI cancer risk in Asians (G vs T: OR = 1.27; 95%CI: 1.07-1.51; GG vs TT: OR = 1.58; 95%CI: 1.05-2.38; TG vs TT: OR = 1.30; 95%CI, 1.01- 1.67; and TG + GG vs TT: OR = 1.38; 95%CI: 1.07-1.78), but not in Caucasians. Further subgroup analysis by cancer type indicated that APE1 Asp148Glu polymorphism may contribute to gastric cancer risk. However, Asp148Glu has no significant association with colorectal or esophageal cancer risk in any genetic model. CONCLUSION: This meta-analysis suggests that the APE1 Asp148Glu polymorphism G allele is associated with an increased GI cancer risk, especially in gastric cancer.

Five common functional polymorphisms in microRNAs (rs2910164, rs2292832, rs11614913, rs3746444, rs895819) and the susceptibility to breast cancer: evidence from 8361 cancer cases and 8504 controls.

OBJECTIVES: To evaluate the relationship between the five common polymorphisms in miRNAs (miR-146a rs2910164 G>C, miR-149 rs2292832 C>T, miR-196a2 rs11614913 C>T, miR-499 rs3746444 A>G and miR-27a rs895819 A>G), and breast cancer (BC) risk. METHODS: Meta-analyses were performed on 15 published studies involving 8, 361 BC patients and 8, 504 cancer-free controls. There were 8 studies with 4, 314 cases and 4, 485 controls for rs2910164, 3 studies with 1, 439 cases and 1, 508 controls for rs2292832, 10 studies with 4, 618 cases and 5, 590 controls for rs11614913, 5 studies with 2, 924 cases and 3, 563 controls for rs3746444, and 5 studies with 2, 912 cases and 3, 697 controls for rs895819. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the BC risk. RESULTS: Meta-analyses showed that rs2910164 (miR-146a) was associated with BC risk in Caucasian population (homozygote comparison: OR = 1.29, 95%CI = 1.02-1.63, P=0.03; dominant model: OR = 1.31, 95% CI = 1.05-1.65, P=0.02), whereas negative results were obtained for Asians in all genetic models. rs11614913 (miR-196a2) was associated with BC risk in the overall population based on the recessive model (OR = 0.89, 95% CI = 0.80-0.99, P=0.03). Association of rs3746444 (miR-499) with BC risk was detected under three genetic models (allele contrast genetic model: OR = 1.13, 95%CI = 1.03-1.23, P=0.007; homozygote comparison: OR = 1.36, 95 %CI = 1.10-1.69, P=0.005 and recessive model: OR = 1.38, 95% CI = 1.12-1.70, P=0.003). When stratified by ethnicity, the effects remained in Asians. rs895819 (miR-27a) was associated with BC risk in the overall population based on the allele contrast genetic model (OR = 0.91, 95%CI = 0.85-0.98, P=0.02); heterozygote comparison (OR = 0.89, 95 %CI = 0.80-0.99, P=0.03) and the dominant model (OR = 0.89, 95% CI = 0.80-0.98, P=0.02). However, there was no association between rs2292832 (miR-149) polymorphism and BC susceptibility. CONCLUSION: Our meta-analysis results suggested that the rs2910164 and rs3746444 polymorphisms are associated with increased BC risk, while the rs11614913 and rs895819 polymorphisms correlate with reduced BC risk.

Associations between C1772T polymorphism in hypoxia-inducible factor-1α gene and breast cancer: a meta-analysis.

BACKGROUND: A meta-analysis was performed to estimate the association between HIF-1α polymorphism (C1772T) and breast cancer risk. MATERIAL AND METHODS: The relevant published literature was retrieved from PubMed, Web of Knowledge, and Embase. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations. RESULTS: Six case-control studies, including 2043 cases and 2146 controls were identified. Meta-analysis showed that there was no marked association between C1772T polymorphism and breast cancer risk in the overall population in the dominant model. The subgroup analysis showed an increased breast cancer risk in Asians based on homozygote comparison and the recessive model. There were no associations between C1772T polymorphism with clinicopathological parameters and habits. CONCLUSIONS: The present meta-analysis suggests that HIF-1α C1772T polymorphism is a risk factor for susceptibility to breast cancer in Asians.

Association between genetic polymorphisms in AURKA (rs2273535 and rs1047972) and breast cancer risk: a meta-analysis involving 37,221 subjects.

BACKGROUND: Published data on the association between AURKA polymorphisms and breast cancer (BC) risk are inconclusive. This meta-analysis was performed to derive a more precise estimation on the relationship between AURKA polymorphisms (rs2273535 and rs1047972) and BC risk. METHODS: PubMed, Web of Knowledge and Embase were searched for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of associations. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for allele contrast genetic model, homozygous genetic model, heterozygote genetic model, dominant model, and recessive model, respectively. RESULTS: A total of 13 studies (16,349 BC patients and 20,872 case-free controls) were involved in this meta-analysis. Meta-analysis showed that there was significant association between rs2273535 and BC risk in three genetic models in the overall population (A vs. T: OR = 1.08, 95% CI = 1.01-1.15, P = 0.02; AA vs. TT: OR = 1.36, 95% CI = 1.06-1.73, P < 0.00001; AA vs. TT + TA: OR = 1.15, 95% CI = 1.01-1.31, P = 0.04). In the subgroup analysis by ethnicity, the effects remained in Asians (allele contrast genetic model: OR = 1.12, 95% CI = 1.00-1.26, P = 0.04 and homozygote comparison: OR = 1.22, 95% CI = 1.06-1.41, P = 0.007). However, no genetic models reached statistical association in Cauasians. Rs1047972 polymorphism was associated with BC risk in the overall population based on homozygote comparison (AA vs. GG: OR = 0.81, 95% CI = 0.66-0.99, P = 0.04). When stratified by ethnicity, rs1047972 polymorphism had a decreased association with BC risk in Caucasians based on allele contrast genetic model, homozygote comparison, the dominant model and the recessive model. However, there was no association in any genetic model in Asians. CONCLUSIONS: This meta-analysis suggests that AURKA rs2273535 polymorphism has an increased risk with BC, especially in Asians. However, rs1047972 polymorphism has a decreased BC risk in Caucasians. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

Association of the three common SNPs of cyclooxygenase-2 gene (rs20417, rs689466, and rs5275) with the susceptibility of breast cancer: an updated meta-analysis involving 34,590 subjects.

Several single nucleotide polymorphisms have been identified in cyclooxygenase-2 (COX-2) genes (e.g., -765 G>C (rs20417), -1195G>A (rs689466), and 8473 C>T (rs5275)). The association of these SNPs with the risk of different cancer types is still controversial. This study aims to evaluate the correlation between these SNPs and breast cancer risk in different ethnic groups. We have searched PubMed, Web of Knowledge, and Embase for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of the associations. A total of 13 studies (15,330 cases and 19,260 controls) were eligible for meta-analysis. This meta-analysis showed that COX-2 rs20417 polymorphism was correlated with an increased risk of breast cancer in Caucasians, while rs689466 was associated with a decreased risk of breast cancer in Caucasians. The rs5275 polymorphism had no association with breast cancer risk.

Functional promoter -765 G > C variant in COX-2 gene is associated with the susceptibility of breast cancer in Chinese Han women.

BACKGROUND: Cyclooxygenase (COX) is a rate-limiting enzyme in prostaglandins synthesis which exists in two isoforms, COX-1 and COX-2. Over-expression of COX-2 was considered to increase the proliferation and enhance the invasiveness of breast cancer cells. It was suggested that genetic variations in COX-2 could influence its expression. Herein, the present study was aimed to investigate the associations between two mostly studied functional polymorphisms (-765 G > C and 8473 C > T) in COX-2 and breast cancer risk in Chinese Han women. METHODS: In the hospital-based case-control study, 465 breast cancer patients and 799 cancer-free controls were genotyped for the COX-2 -765 G > C and 8473 C > T polymorphisms using TaqMan assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using the logistic regression. RESULTS: Compared with the wild genotype of -765 G > C, we found a statistically significant increased risk of breast cancer associated with the variant genotypes [GC/CC vs. GG: OR = 1.56, 95% CI = 1.11-2.21]. In the stratified analysis, the increased risk was more predominant among the subgroups of younger subjects (OR = 1.61, 95% CI = 1.00-2.61). Furthermore, the variant genotypes were associated with large tumor size (OR = 3.01, 95% CI = 1.47-6.12). No significant association was observed for the 8473 C > T polymorphism. CONCLUSIONS: Our results suggest that the functional -765 G > C polymorphism in the promoter of COX-2 may influence the susceptibility and progression of breast cancer in the Chinese Han population.