Dongmei Wu

Nanjing Medical University, Nan-ching, Jiangsu Sheng, China

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Publications (25)76.51 Total impact

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    ABSTRACT: Recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has identified two novel single nucleotide polymorphisms (SNPs) rs11066280 and rs2074356 on C12orf51 gene. We hypothesized that SNPs rs11066280 and rs2074356 could influence gastric cancer survival outcomes. We genotyped the SNPs rs11066280 and rs2074356 in 940 patients with surgically resected gastric cancer. Analyses of genotype association with survival outcomes were assessed by the Kaplan-Meier method, Cox proportional hazards models and the log-rank test. There was no significant association between rs11066280 and survival of gastric cancer. However, in the stratification analysis of histology, we found that the rs11066280 TA/AA genotypes were associated with a poor survival of intestinal-type gastric cancer (log-rank P = 0.041, hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.02–1.93), Moreover, this hazardous effect was more prominent among patients with tumor size > 5 cm, no distant metastasis, chemotherapy and drinking. No significant association was observed between rs2074356 and the survival of gastric cancer. C12orf5 rs11066280 could be useful marker of survival assessment and individualized clinical therapy for gastric cancer, particularly among the intestinal-type gastric cancer.
    Biomedicine & Pharmacotherapy. 11/2014;
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    ABSTRACT: Single nucleotide polymorphisms (SNPs) in the 3′-untranslated regions (UTRs) targeted by putative mircoRNAs (miRNAs) could influence the susceptibility of cancer. Recently, miR-29c has been reported to be down-regulated in gastric cancer (GC) and serve as a tumor suppressor that regulated tumor progression. The present study was aimed at investigating whether the miR-29c binding site SNPs within the 3′-UTRs of target genes affected the gastric cancer risk. Using bioinformatics tools, we chose three SNPs (IGHMBP2 rs3750980, LAMTOR3 rs11944405 and WWOX rs2288035) located in miR-29c binding sites. We genotyped these three SNPs to assess their associations with GC risk in a case-control study comprising 753 GC cases and 950 controls. Among these three SNPs, we found a significantly decreased risk of GC associated with the LAMTOR3 rs11944405 T > C polymorphism [TC vs. TT, adjusted odds ratio (OR) = 0.79, 95% confidence interval (CI) = 0.63–0.99; TC/CC vs. TT, adjusted OR = 0.81, 95% CI = 0.65–1.00]. The significant association was also presented in the subgroup analysis by age (≤ 65), sex (female), depth of invasion (T3/T4), lymph node metastasis (N1-3), distant metastasis (M0) and TNM stage (III/IV). However, no significant association was detected for IGHMBP2 rs3750980 and WWOX rs2288035. Our results suggested that the LAMTOR3 rs11944405 polymorphism may be a potential biomarker for genetic susceptibility to GC.
    Biomedicine & Pharmacotherapy. 11/2014;
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    ABSTRACT: Background Global miRNA expression profile has been widely used to characterize human cancers. It is well established that genetic variants in miRNAs can modulate miRNA biogenesis and disease risk. Methods Genome-wide miRNA microarray was employed for assessment of miRNA expression profile of gastric adenocarcinoma (GAC). The variants of significantly dysregulated miRNA were genotyped in test (715 cases and 804 controls) and validation (940 cases and 1050 controls) subject sets. Results MiRNA microarray revealed that 12 miRNAs including miR-107 significantly dysregulated in GAC tissues. The sequencing of the promoter of miR-107 identified 3 SNPs (rs11185777, rs78591545, and rs2296616) with minor allele frequency (MAF) > 5%. Analyzing their association with GAC risk and prognosis revealed that the C allele of rs2296616 (T > C) was significantly associated with the decreased risk of GAC among the test, validation and combined sets (TC/CC vs. TT, adjusted OR = 0.39, 95% CI = 0.31–0.49 for the combined set). However, the C allele was related to an unfavorable prognosis of Cardia GAC (CGAC) (adjusted HR = 1.49, 95% CI = 1.01–2.20). In vivo evidence showed that the individuals with the rs2296616C allele had lower miR-107 expression compared with the homozygous T allele carriers. Conclusion miR-107 is dysregulated in GAC pathogenesis and the SNP rs2296616 may play a role in the process.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2014; 769:35–41. · 3.90 Impact Factor
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    ABSTRACT: Single-nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) have been suggested to influence the occurrence and progression of cancer through altering the expression and biological function of miRNAs. The aim of this study was to investigate whether the potential functional SNPs in MIR196A2 promoter had effect on the susceptibility to gastric cancer (GC) in a Chinese population.We conducted a 2-stage case-control study (753 cases and 854 controls in testing set; 940 cases and 1061 controls in validation set) to evaluate the association between 2 potential functional SNPs in MIR196A2 promoter (rs12304647 A>C and rs35010275 G>C) and GC risk. The luciferase reporter assay and electrophoretic mobility shift assay were used to examine the functionality of the important polymorphism.We found that the rs35010275 C allele was significantly associated with the decreased risk of GC (adjusted odds ratio = 0.85, 95% confidence interval = 0.77-0.94) in the combined case-control studies. The miR-196a expression levels in GC tissues were significantly higher than that in corresponding adjacent normal tissues (P < 0.001). Besides, each allele of rs35010275 displayed completely opposite effects to influence the transcription activity of MIR196A2 promoter via recruiting different transcription factors or complexes.The functional rs35010275 G>C polymorphism in MIR196A2 promoter was significantly associated with miR-196a expression and influenced the genetic susceptibility to GC.
    Medicine. 11/2014; 93(26):e173.
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    ABSTRACT: Background Many studies have linked ambient fine particulate matter (PM2.5) air pollution to different cardiopulmonary diseases in the general population. However the complex mechanisms underlying PM2.5-induced adverse health effects are not yet to be fully elucidated. Method In this study, we aimed to identify genes and pathways that may contribute to PM2.5-induced lung toxicity in humans through genome-wide approaches. Human bronchial epithelial (HBE) cells, exposed to various concentrations of PM2.5 collected from Wuhan, China, showed decreased cell viability in a dose-dependent manner. HBE cells were exposed to 200 μg/ml and 500 μg/ml PM2.5 and microarrays were used to obtain a global view of the transcriptomic responses. Results A total of 970 and 492 genes were identified that significantly changed after 200 μg/ml and 500 μg/ml PM2.5 exposures, respectively. PM2.5 induced a large number of genes involved in inflammatory and immune response, response to oxidative stress, and response to DNA damage stimulus, which might contribute to PM2.5 related cardiopulmonary diseases. Pathway analysis revealed that different dose of PM2.5 triggered partially common disturbed pathways. Flow cytometry assay evidenced that there were statistically significant differences in the G1 phase of cell cycle after low or high-dose PM2.5 exposure when compared to the unexposed controls. Only high-dose PM2.5 significantly decreased the proportion of cells in the S phase of cell cycle. Conclusion We identified many genes and pathways that altered significantly in HBE cells after PM2.5 exposures. These findings are important in providing further understanding of the mechanisms underlying PM2.5-induced adverse health effects.
    Toxicology Letters 07/2014; · 3.15 Impact Factor
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    ABSTRACT: Single nucleotide polymorphisms (SNPs) in the 3'-untranslated regions targeted by putative mircoRNA can change its binding strength, affecting the susceptibility and prognosis of cancer. We aimed to investigate the associations between SNPs within miR-148a binding sites and gastric cancer (GC) risk and prognosis. Using bioinformatics tools, we selected two SNPs (SCRN1 rs6976789 and PDYN rs2235749) located in miR-148a target sites. We genotyped the two SNPs in a case-control study comprising 753 GC patients and 949 cancer-free subjects. We found a significantly increased risk of GC associated with the SCRN1 rs6976789 C>T polymorphism [adjusted OR = 1.25, 95% confidence interval (CI) = 1.02-1.53; CT/TT vs. CC]. However, no significant association was found between the PDYN rs2235749 and GC risk in all genetic models. Furthermore, we evaluated whether SCRN1 rs6976789 affected the survival of GC patients. Results showed that individuals with SCRN1 rs6976789 TT genotype had poorer overall survival compared with those carried CC/CT genotypes in intestinal-type GC (adjusted HR = 2.47, 95% CI = 1.21-5.05). Luciferase report assay showed that the rs6976789 variant T allele influenced the binding ability of miR-148a. Our results suggested that the SCRN1 rs6976789 polymorphism may play an important role in the GC development and progression.
    Scientific reports. 01/2014; 4:7080.
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    ABSTRACT: A recent genome-wide association study (GWAS) on esophageal squamous-cell carcinoma (ESCC) among Chinese people has discovered a novel single nucleotide polymorphism (SNP) rs10484761 on 6p21.1 region. We hypothesized that SNP rs10484761 T/C is associated with survival of gastric cancer. We genotyped SNP rs10484761 in 940 gastric cancer patients treated with surgical resection. Kaplan-Meier survival analysis, log-rank test, and Cox proportional hazard models were used to evaluate the association between the SNP rs10484761 and gastric cancer survival. In the dominant model, those who carrying TC/CC genotypes had a significant shorter survival time (log-rank P=0.05), especially in the subgroups of aged male patients, cardia intestinal tumor (HR=1.41, 95% CI=1.08-1.84 for cardia cancer and HR=1.64, 95% CI=1.14-2.37 for intestinal-type), tumor size≤5cm (HR=1.41, 95% CI=0.56-0.99), T1 depth invasion (HR=2.34, 95% CI=1.20-4.56), lymph node metastasis (HR=1.51, 95% CI=1.19-1.96), no distant metastasis (HR=1.33, 95% CI=1.05-1.68), TNM stage III+IV (HR=1.50, 95% CI=1.13-1.98), and with chemotherapy (HR=1.53, 95% CI =1.17-1.99). The results indicated that SNP rs10484761 was associated with prognosis of gastric cancer, suggesting that this genetic variant may serve as a potential marker to predict the survival of gastric cancer in Chinese population.
    Gene 12/2013; · 2.20 Impact Factor
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    ABSTRACT: Acute lymphoblastic leukemia (ALL) is a major cause of mortality and morbidity in childhood, and the causes of ALL are not completely understood. microRNAs (miRNAs) regulate various biological processes including organ development, cell growth regulation, cell differentiation, apoptosis, and tumorigenesis. We performed a case-control study with 570 childhood ALL cases and 673 cancer-free controls to investigate the association between hsa-miR-196a2 rs11614913 T>C polymorphism and ALL risk. The bioinformatics was used to estimate the potential target of hsa-miR-196a2. In the present study, the hsa-miR-196a2 variant TC heterozygote, and CC/TC genotypes were found to be associated with a significantly increased childhood ALL risk, compared with the TT wild-type homozygote (adjusted OR=1.50, 95% CI=1.15-1.95 for TC and OR=1.40, 95%CI=1.09-1.79 for CC/TC). Further, the difference was pronounced in younger (≤ 6) subjects or parental non-drinker. The significance of the increased risk is more obvious than the higher treatment branch. Additionally, we found that the rs11614913 TC genotype can increase B-phenotype ALL risk (OR=1.37, 95% CI=1.07-1.76). Finally, combination of three bioinformatics approaches revealed that HOXC8 may be the target gene of hsa-miR-196a2. Taken together, our finding suggested that hsa-miR-196a2 rs11614913 T>C may increase the risk of childhood ALL. Large studies with the function of hsa-miR-196a2 are needed in the further study.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 11/2013; · 3.90 Impact Factor
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    ABSTRACT: P53 is a tumor suppressor gene and plays important role in the etiology of breast cancer. Intron 3 sixteen-bp duplication polymorphism of p53 has been reported to be associated with breast cancer risk. However, the reported results remain conflicting rather than conclusive. A meta-analysis including 19 case-control studies was performed to address this issue. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to evaluate the association. THE OVERALL RESULTS SUGGESTED THAT THE VARIANT GENOTYPES WERE ASSOCIATED WITH A SIGNIFICANTLY INCREASED BREAST CANCER RISK (DEL/INS VS DEL/DEL: OR = 1.18, 95% CI: 1.00-1.40; Ins/Ins vs Del/Del: OR = 1.42, 95% CI = 1.09-1.84; Ins/Ins+Del/Ins vs Del/Del: OR = 1.21, 95% CI = 1.03-1.41). When stratifying by sample size of studies, a significantly elevated risk was also observed among large sample studies (>500 subjects) but not among small sample studies (≤500 subjects). These results suggested that the 16-bp duplication polymorphism of p53 may contribute to susceptibility to breast cancer. Additional well-designed large studies were required to validate this association in different populations.
    PLoS ONE 04/2013; 8(4):e61662. · 3.53 Impact Factor
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    ABSTRACT: ERCC4 plays an essential role in the nucleotide excision repair (NER) pathway, which is involved in the removal of a wide variety of DNA lesions. To determine whether the ERCC4 tagging SNPs (tSNPs) are associated with risk of gastric cancer, we conducted a hospital-based case-control study of 350 cases and 468 cancer-free controls. In the logistic regression (LR) analysis, we found a significantly decreased risk of gastric cancer associated with the rs744154 GC/CC genotypes [adjusted odds ration (OR)=0.56, 95% confidence interval (CI)=0.42-0.75, false discovery rate (FDR) P=0.012] compared with the wild-type GG genotype. Haplotype-based association study revealed that the CGC haplotype that containing the rs744154 C allele can decrease the risk of gastric cancer compared with the most common haplotype GGT (adjusted OR=0.61, 95% CI=0.46-0.81). Using the multifactor dimensionality reduction (MDR) analysis, we identified that the SNP rs744154 and smoking status were the best two predictive factors for gastric cancer with an testing accuracy of 55.76% and a perfect cross-validation consistency (CVC) of 10 (P=0.001). Furthermore, the smokers with the rs744154 GC/CC genotypes showed a decreased risk of gastric cancer (adjusted OR=0.55, 95% CI=0.35-0.85) compared with the smokers with the GG genotype using multivariate LR analysis. The above findings consistently suggested that genetic variants in the ERCC4 gene may play a protective role in the etiology of gastric cancer, even in the smokers.
    Gene 03/2013; · 2.20 Impact Factor
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    ABSTRACT: Polymorphisms of the DNA repair gene X-ray repair cross-complementing protein 1 (XRCC1) Arg194Trp, Arg280His, and Arg399Gln have been shown to alter the DNA repair activity and to be associated with genetic susceptibility to several types of cancer. We indentified genotypes of 944 surgically resected gastric cancer (GC) patients by the SNaPshot method to investigate the association of these polymorphisms with clinical progression and outcomes of GC in a Chinese population. The XRCC1 codon 280 His carriers (Arg/His+His/His) held a significantly lower risk of distant metastasis in the dominant model (Pearson chi-square test P=0.019). A weak association of these cases with reduced risk of lymph node metastasis was also found (Pearson chi-square test P=0.051). Individuals carrying at least one Trp allele of XRCC1 codon 194 had an increased risk of death compared with those with Arg/Arg homozygotes in diffuse-type GC (adjusted hazard ratio=1.34, 95% confidence interval=1.05-1.71). Our findings demonstrated that the genetic variant Arg280His in XRCC1 may contribute to cancer progression and that XRCC1 Arg194Trp variants may act as a favorable prognostic indicator of resected GC, particularly among the diffuse-type GC. Larger studies are needed to verify our results in different populations.
    DNA and cell biology 03/2013; 32(3):111-8. · 2.28 Impact Factor
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    ABSTRACT: PURPOSE: Several studies have examined the prognostic value of the TP53 Arg72Pro polymorphism (rs1042522) and/or MDM2 SNP309 (rs2279744) in multiple tumors. Our aim was to determine whether these two genetic variants were correlated with clinical outcome of gastric cancer. METHODS: We genotyped the two SNPs, TP53 codon 72 polymorphism and MDM2 SNP309, in 940 gastric cancer patients with complete follow-up information and analyzed the correlation between the SNPs and gastric cancer survival. RESULTS: The two SNPs were not significantly associated with gastric cancer survival. However, the TP53 codon 72 polymorphism had a prominent correlation with clinical outcome of patients receiving 5-fluorouracil (5-Fu)-based postoperative chemotherapy [Arg/Arg + Arg/Pro vs. Pro/Pro, adjusted hazard ratio (HR) = 1.63, 95 % confidence interval (CI) = 1.08-2.44]. Moreover, the unfavorable effect of Arg allele on survival outcome was more predominant for subgroups of older (age >60 years), male, intestinal histology type, advanced stage (T3/T4), and none metastasis of lymph node (N0) or distant (M0) (adjusted HR = 2.34, 95 % CI = 1.24-4.44 for age >60 years; 1.72, 1.10-2.69 for male; 2.30, 1.10-4.80 for intestinal; 1.62, 1.01-2.59 for T3/T4; 3.42, 1.26-9.24 for N0; and 1.62, 1.06-2.47 for M0). Among multiple chemotherapy regimens, the association was only significant in the subgroup of 5-Fu/calcium folinate plus oxaliplatin (FOLFOX) chemotherapy regimen (adjusted HR = 4.47, 95 % CI = 1.21-16.55). CONCLUSIONS: Our findings showed that TP53 codon 72 polymorphism was associated with survival of gastric cancer patients treated with 5-Fu-based postoperative chemotherapy. The codon 72 polymorphism may be a potential prognostic factor.
    Cancer Chemotherapy and Pharmacology 02/2013; · 2.80 Impact Factor
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    ABSTRACT: Genetic variations in miRNAs have been demonstrated to be capable of altering miRNA expression, consequently affecting many cancer-related biological processes. The MIR196A2 rs11614913 (T > C) polymorphism has been reported to be associated with various cancers development and progression. In our study, we aim to explore whether this polymorphism is relevant to the genetic susceptibility and prognosis of gastric cancer in a Chinese population. We analyzed the correlations of rs11614913 polymorphism with gastric cancer susceptibility in test and validation sets. The test set comprised 749 cases and 900 controls, while the validation set enrolled 940 cases and 1046 controls. Moreover, we evaluated the association between the polymorphism and gastric cancer prognosis in the validation set with follow-up information. The variant rs11614913 CC genotype was associated with a significantly reduced risk of gastric cancer in both sets (adjusted odds ratio [OR] = 0.78, 95% confidence interval [CI] = 0.62-0.99 for the test set and 0.64, 0.52-0.80 for the validation set) compared with the CT/TT genotypes. Furthermore, the CC genotype was associated with a significantly increased survival of gastric cancer compared with the CT/TT genotypes (adjusted hazard ratio [HR] = 0.72, 95% CI = 0.55-0.95), and the association was more prominent among patients with non-cardia gastric cancer than those with cardia gastric cancer (adjusted HR = 0.57, 95% CI = 0.40-0.83 for NCGC and 1.00, 0.65-1.53 for CGC). Our results suggested that the genetic variation of MIR196A2 may play a role in gastric cancer tumorigenesis. © 2013 Wiley Periodicals, Inc.
    Molecular Carcinogenesis 02/2013; · 4.27 Impact Factor
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    ABSTRACT: As an imperative part of PI3K/Akt/mTOR pathway, mammalian target of rapamycin (mTOR) has been demonstrated to increase in gastric cancer cells and tumors. Our research explored the relationship between single nucleotide polymorphism (SNP) rs2295080 in mTOR promoter region and the risk of gastric cancer (GC). Seven hundred and fifty-three (753) gastric adenocarcinoma patients and 854 matched healthy subjects were recruited in the cancer association study and 60 tissues were used to test the expression of mTOR. Unconditional logistic regression was selected to evaluate the association between the rs2295080 T>G polymorphism and GC risk. We then examined the functionality of this promoter genetic variant by luciferase assay and EMSA. Individuals with G allele had a 23% decreased risk of GC, comparing with those carrying T allele (adjusted OR = 0.77, 95% CI = 0.65-0.92). This protective effect of G allele stood out better in male group. Meanwhile, GC patients carrying TG/GG genotype also displayed a decreased mRNA level of mTOR (P = 0.004). In luciferase assay, T allele tended to enhance the transcriptional activity of mTOR with an approximate 0.5-fold over G allele. Furthermore, EMSA tests explained that different alleles of rs2295080 displayed different affinities to some transcriptional factor. The mTOR promoter polymorphism rs2295080 was significantly associated with GC risk. This SNP, which effectively influenced the expression of mTOR, may be a new biomarker of early diagnosis of gastric cancer and a suitable indicator of utilizing mTOR inhibitor for treatment of GC.
    PLoS ONE 01/2013; 8(3):e60080. · 3.53 Impact Factor
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    ABSTRACT: Human telomerase reverse transcriptase (TERT) is essential for the maintenance of telomere DNA length, chromosomal stability, and cellular immortality. We hypothesized that TERT polymorphisms are associated with risk of childhood acute lymphoblastic leukemia (ALL). We first conducted a case-control study of 570 ALL cases and 673 cancer-free controls of Chinese children, using the tagging single-nucleotide polymorphisms (tSNPs) approach. We then examined the functionality of the important SNPs. We found that TERT promoter region tSNP (rs2735940) and two intron region tSNPs (rs2736100 and rs10069690) were associated with risk of childhood ALL (P = 0.036, 0.011 and 0.022, respectively, in allele comparison). The in vitro luciferase assays in Jurkat cells showed an increased transcriptional activity of rs2735940 T allele compared with the C allele. Additional experiments with ALL bone marrow revealed that the rs2735940 T allele increased levels of the TERT mRNA. Notably, TERT intron 2 polymorphism (rs2736100) was associated with lower telomerase activity and longer telomeres. Our findings suggested that TERT promoter rs2735940 polymorphism may affect the TERT activity and rs2736100 may be associated with telomere function, and thus, is a potential biomarker for genetic susceptibility to ALL in Chinese children.
    Carcinogenesis 10/2012; · 5.64 Impact Factor
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    ABSTRACT: 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.
    Mutagenesis 10/2012; · 3.50 Impact Factor
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    ABSTRACT: Gastric cancer is the second leading cause of cancer-related death worldwide with a low 5-year survival (S5y) after initial diagnosis. Although aberrant Wnt/β-catenin (CTNNB1) signaling has been observed in multiple human cancers, there is no information on the role of CTNNB1 polymorphisms in gastric cancer risk and S5y. We performed a genetic association study to analyse the correlation between the five tagged SNPs (tSNPs) (rs4135385, rs1798808, rs1880481, rs11564465 and rs2293303) of CTNNB1 and gastric cancer risk and survival. A total of 944 patients with complete follow-up information and 848 cancer-free controls were enrolled in this study. The rs1880481 polymorphism was correlated with decreased risk of gastric cancer [AC/AA vs. CC: adjusted odds ratio (OR) = 0.76, 95% confidence interval (CI) = 0.63-0.91], whereas the three other SNPs showed opposite effect (AG/AA vs. GG: adjusted OR = 1.31, 95% CI = 1.08-1.57 for rs4135385; GG vs. AA/AG: 2.09, 1.02-4.28 for rs11564475; TT vs. CC/CT: 4.87, 2.72-8.71 for rs2293303). We further investigated if these tSNPs were related to the S5y of gastric cancer, and the results displayed that only the SNP rs4135385 AG/AA genotypes were significantly associated with a favorable gastric cancer survival compared with the GG genotype [adjusted hazard ratio (HR) = 0.80, 95% CI = 0.66-0.97], and the association was more prominent among patients with non-cardia gastric cancer (NCGC) than those with cardia gastric cancer (CGC) (Log-rank P = 0.007 for NCGC and 0.417 for CGC). Our results indicated that the genetic variants of CTNNB1 could be used as predictors of gastric cancer susceptibility and prognosis.
    Mutagenesis 07/2012; · 3.50 Impact Factor
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    ABSTRACT: BACKGROUND: Excessive reactive oxygen species (ROS) accumulation is a common phenomenon in carcinogenesis. However, the rationale behind ROS involvement in gastric cancer is unclear. In this study, the authors investigated the clinical significance of the single nucleotide polymorphisms (SNPs) of 2 ROS metabolic process-related genes: superoxide dismutase 2 (SOD2) and glutathione S-transferase π (GSTP1). METHODS: In total of 929 patients with gastric cancer who had definitive clinicopathologic and follow-up data were collected. SOD2 reference SNP 4880 (rs4880) and GSTP1 rs1695 genotyping were examined in DNA samples extracted from paraffin-embedded tumor tissue. Association of the 2 SNPs with each clinicopathologic feature was analyzed using the Pearson chi-square test and the independent Student t test. Gastric cancer-specific overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Multivariate Cox regression analyses of these SNPs also were performed. RESULTS: The SOD2 rs4880 CT + CC genotypes were significantly associated with a high level of lymph node metastasis (P = .023), whereas the GSTP1 rs1695 GA + GG genotypes were significantly associated with larger tumor size (>5 cm long; P = .048). Kaplan-Meier and Cox regression data indicated that the SOD2 rs4880 CT + CC genotypes alone (hazard ratio, 1.299; 95% confidence interval, 1.053-1.603; P = .015) and the GSTP1 rs1695 GA + GG combined genotypes (hazard ratio, 1.496; 95% CI, 1.078-2.074; P = .016) were independent predictors for overall survival. CONCLUSIONS: The current data, based on a large cohort (n = 929) of Chinese patients with gastric cancer, suggested that the presence of SOD2 rs4880 and GSTP1 rs1695 genotypes may contribute to cancer progression as well as tumor aggressiveness. The components of ROS metabolism pathways may be potential therapeutic targets for this aggressive malignancy. Cancer 2012. © 2012 American Cancer Society.
    Cancer 04/2012; · 5.20 Impact Factor
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    ABSTRACT: 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. 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. 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. 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.
    Journal of Cancer Research and Clinical Oncology 04/2012; 138(8):1339-45. · 2.91 Impact Factor
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    ABSTRACT: Two genome-wide association studies on gastric cancer showed a previously unknown gastric cancer susceptible locus in PLCE1 at 10q23. We hypothesized that the single nucleotide polymorphism (SNP) rs2274223 A/G is associated with the survival rate of gastric cancer. We genotyped the above SNP in 940 gastric cancer patients to investigate the association between the polymorphism and gastric cancer survival by the TaqMan method. We found that patients carrying PLCE1 rs2274223 AA genotype survived for a significantly shorter time than those carrying the AG and GG genotypes (log-rank P = 0.046). This significance was enhanced in the dominant model (AA vs. AG/GG, log-rank P = 0.014). Multivariate Cox regression analyses showed that the AG/GG genotypes were associated with a significantly decreased risk of death from gastric cancer [adjusted hazard ratio (HR) = 0.79, 95% confidence interval (CI) = 0.65-0.95]. Most of stratification analysis did not find an enhanced association between the same genotype and prognosis, except for patients with TNM stage III disease (HR = 0.63, 95% CI = 0.48-0.83). Our findings showed that the PLCE1 SNP rs2274223 was associated with significantly improved gastric cancer survival in a Chinese population. Further functional studies are needed to validate our results.
    Journal of Gastroenterology 08/2011; 46(11):1260-6. · 3.79 Impact Factor

Publication Stats

147 Citations
76.51 Total Impact Points

Institutions

  • 2008–2014
    • Nanjing Medical University
      • • Cancer Center
      • • Department of Molecular and Genetic Toxicology
      • • Key Laboratory of Reproductive Medicine
      • • Jiangsu Province Key Laboratory of Reproductive Medicine
      Nan-ching, Jiangsu Sheng, China