State Key Laboratory of Environment Health Incubation

Wuhan, China

State Key Laboratory of Environment Health Incubation

Wuhan, China
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Jiang Y.,State Key Laboratory of Environment Health Incubation | Jiang Y.,Key Laboratory of Environment and Health | Jiang Y.,Huazhong University of Science and Technology | Chen X.,State Key Laboratory of Environment Health Incubation | And 17 more authors.
Human and Experimental Toxicology | Year: 2013

Benzo(a)pyrene (BaP), a typical environmental carcinogen, can induce cell death both by protein 53 or tumor protein 53 (p53)-independent and -dependent pathways. However, little is known about themolecular mechanisms of p53-independent pathways in BaP-induced cell death. In this study, cells with different genetic background (including p53-proficient human fetal lung fibroblast cell lines (MRC-5), p53-deficient human non-small-cell lung carcinoma cell lines (H1299), and p53-knockdown cell lines (MRC-5p53-1-)) were used to establishmodels of BaP-induced cell death. The results showed that BaP (8, 16, 32, and 64 mM) induced necroptotic cell death in the cell lines. The necroptotic cell death andDNAdamagewere concurrently observed. In the three cell lines, at 24 h after treatment, BaP (8-64 mM) upregulated expressions of BAX, BCL-2, and cleaved caspase-3 proteins, but not their messenger RNAlevels. The findings suggested that BaP-induced necroptosis wasmodulated by the p53-independent pathway, which was related to the induction of BAX, decreased expression of BCL-2, and activation of caspase-3. © The Author(s) 2013.


Zhang Y.,State Key Laboratory of Environment Health Incubation | Yi P.,Huazhong University of Science and Technology | Chen W.,State Key Laboratory of Environment Health Incubation | Ming J.,Huazhong University of Science and Technology | And 16 more authors.
Tumor Biology | Year: 2014

Recent publications have found associations between single-nucleotide polymorphisms (SNPs) in 8q24 and the risk of breast cancer (BC) in some populations, but the conclusions are inconsistent. In order to further investigate the association between variants in this region and BC risk in Chinese population, we conducted an independent hospital-based case-control study to discern the effects of these SNPs on BC risk. We genotyped three 8q24 SNPs (rs13281615, rs6983267, and rs9642880) in 485 cases and 530 cancer-free controls. The results indicated that the rs13281615 G allele significantly increased BC risk, with an odds ratio (OR) of 1.23 (95 % confidence interval (CI) = 1.03-1.46) under the allelic model. Besides, stratification analysis reported that the significant association remained in the estrogen receptor (ER)+/progesterone receptor (PR)+ subgroup with a P value of 0.007 under the allelic model (OR = 1.33, 95 % CI = 1.08-1.63). For the rs9642880 variant, only a feeble association was observed for the GT genotype compared with the GG genotype (OR = 1.33, 95 % CI = 1.01-1.74). In addition, there was a negligible association between rs6983267 and BC risk in the ER-/PR- subgroup. However, no significant finding was observed in the overall participants. The findings suggested that polymorphisms in 8q24 may contribute to susceptibility to BC risk. However, functional studies are warranted to further elucidate the mechanisms of the association. © 2014 International Society of Oncology and BioMarkers (ISOBM).


Gong J.,State Key Laboratory of Environment Health Incubation | Gong J.,Huazhong University of Science and Technology | Tian J.,State Key Laboratory of Environment Health Incubation | Tian J.,Huazhong University of Science and Technology | And 19 more authors.
Carcinogenesis | Year: 2016

Genome-wide association studies (GWASs) have identified multiple susceptibility loci of colorectal cancer (CRC), however, causative polymorphisms have not been fully elucidated. Long non-coding RNAs (lncRNAs) are a recently discovered class of non-protein coding RNAs that involved in a wide variety of biological processes. We hypothesized that single nucleotide polymorphisms (SNPs) in lncRNA may associate with the CRC risk by influencing lncRNA functions. To evaluate the effects of SNPs on CRC susceptibility in Chinese populations, we first screened out all potentially functional SNPs in exons of lncRNAs located in CRC susceptibility loci identified by GWAS. Eight SNPs were selected and genotyped in 875 CRC cases and 855 controls and replicated in an independent case-control study consisting of 768 CRC cases and 768 controls. Analyses showed that CG and GG genotypes of the rs2147578 were significantly associated with increased risk for CRC occurrence in both case-control studies [combined analysis OR = 1.29; 95% confidence interval (CI) = 1.11-1.51, P = 0.001] compared to the rs2147578 CC genotype. Bioinformatics analyses showed that rs2147578 is located in the transcript of lnc-LAMC2-1:1 and could influence the binding of lnc-LAMC2-1:1/miR-128-3p. Further luciferase reporter assays demonstrated that the construct with the risk rs2147578G allele had relatively high expression activity compared with that of the rs2147578C allele. Expression quantitative trait loci analyses also showed that rs2147578 is correlated with the expression of a well established oncogene LAMC2 (laminin subunit gamma 2). These findings indicated that rs2147578 in lnc-LAMC2-1:1 might be a genetic modifier for the development of CRC. © The Author 2016. Published by Oxford University Press. All rights reserved.


Zhu B.,State Key Laboratory of Environment Health Incubation | Zhu B.,Huazhong University of Science and Technology | Zhu Y.,State Key Laboratory of Environment Health Incubation | Zhu Y.,Huazhong University of Science and Technology | And 28 more authors.
Oncotarget | Year: 2016

Pancreatic cancer (PC) is one of the deadliest solid malignancies carrying a gloomy 5-year survival rate less than 5%. The signal transducer and activator of transcription 3 (STAT3) is a common transcriptional regulator, whose aberrant expression has been widely found in human cancers, including PC. Our current study aimed to illustrate the roles of common variants, in the three prime untranslated region (3'UTR) of STAT3, in modifying the risk of PC through two-stage case-control studies integrating biological experiments. We first explored the associations between two common variants (rs1053004 and rs1053005) and PC risk in 774 PC cases and 777 controls. Only rs1053004 T > C showed a significant association with a reduced risk of PC with an odds ratio (OR) and 95% confidence interval (CI) of 0.85 (0.74-0.98). Then we attempted to validate the association in another 940 cases and 1398 controls, and the significant association persisted with OR (95%CI) of 0.86 (0.76-0.97). Dual luciferase reporter gene assays indicated that C allele conferred a higher expression of STAT3 in three PC cell lines including Panc-1 (P = 3.0 × 10-3), BxPC-3 (P = 6.7 × 10-5) and SW1990 (P = 4.0 × 10-3). In conclusion, the current study provided evidence that rs1053004 T > C in 3'UTR of STAT3 may decrease the risk of PC through up-regulating the gene expression.


Zhu B.,State Key Laboratory of Environment Health Incubation | Sun Y.,State Key Laboratory of Environment Health Incubation | Qi L.,Harvard University | Zhong R.,State Key Laboratory of Environment Health Incubation | Miao X.,State Key Laboratory of Environment Health Incubation
Scientific Reports | Year: 2015

Previous epidemiological studies on the relation between dietary legume consumption and risk of colorectal cancer (CRC) remain controversial. We conducted a meta-analysis based on prospective cohort studies to investigate the association between dietary legume consumption and risk of CRC. Fourteen cohort studies were finally included, containing a total of 1903459 participants and 12261 cases who contributed 11628960 person-years. We found that higher legume consumption was associated with a decreased risk of CRC (RR, relative risk = 0.91; 95% CI, confidence interval = 0.84-0.98). Subgroup analyses suggested that higher legume consumption was inversely associated with CRC risk in Asian (RR = 0.82; 95% CI = 0.74-0.91) and soybean intake was associated with a decreased risk of CRC (RR = 0.85; 95% CI = 0.73-0.99). Findings from our meta-analysis supported an association between higher intake of legume and a reduced risk of CRC. Further studies controlled for appropriate confounders are warranted to validate the associations.


Li J.,State Key Laboratory of Environment Health Incubation | Zou L.,State Key Laboratory of Environment Health Incubation | Chen W.,State Key Laboratory of Environment Health Incubation | Zhu B.,State Key Laboratory of Environment Health Incubation | And 6 more authors.
PLoS ONE | Year: 2014

Epidemiological studies have investigated the potential anticancer effects of mushroom intake. This review aims to clarify the evidence on the association of dietary mushroom intake with breast cancer risk and to quantify its dose-response relationship. Relevant studies were identified by a search of PubMed, Web of Science and Google Scholar up to December 31, 2013. Observational studies with relative risks (RRs) or hazard ratios (HRs) or odd ratios (ORs) and 95% confidence intervals (CIs) of breast cancer for three or more categories of mushroom intake were eligible. The quality of included studies was assessed by using Newcastle-Ottawa Scale. A dose-response meta-analysis was performed by utilizing generalized least squares trend estimation. Eight case-control studies and two cohort studies with a total of 6890 cases were ultimately included. For dose-response analysis, there was no evidence of non-linear association between mushroom consumption and breast cancer risk (P = 0.337) and a 1 g/d increment in mushroom intake conferred an RR of 0.97 (95% CI: 0.96-0.98) for breast cancer risk, with moderate heterogeneity (I2 = 56.3%, P = 0.015). Besides, available menopause data extracted from included studies were used to evaluate the influence of menopausal statues. The summary RRs of mushroom consumption on breast cancer were 0.96 (95% CI: 0.91-1.00) for premenopausal women and 0.94 (95% CI: 0.91-0.97) for postmenopausal women, respectively. Our findings demonstrated that mushroom intake may be inversely associated with risk of breast cancer, which need to be confirmed with large-scale prospective studies further. © 2014 Li et al.


Gong J.,State Key Laboratory of Environment Health Incubation | Gong J.,Huazhong University of Science and Technology | Shen N.,State Key Laboratory of Environment Health Incubation | Shen N.,Huazhong University of Science and Technology | And 8 more authors.
Tumor Biology | Year: 2014

Evidence shows that single-nucleotide polymorphisms in microRNA (miRNA) target sites can create, destroy, or modify the miRNA/mRNA binding, therefore modulating gene expression and affecting cancer susceptibility. The transforming growth factor-β (TGF-β) signaling pathway plays a pivotal role in tumor initiation and progression. Intriguingly, recent advances of genome-wide association studies have identified multiple risk loci in this pathway to be associated with risk of colorectal cancer (CRC). To test the hypothesis that genetic variants in miRNA target sites in genes of the TGF-β signaling pathway may also be associated with CRC risk, we first systematically scanned the singlenucleotide polymorphisms (SNPs) in genes of TGF-β signaling pathway which potentially affect the miRNA/mRNA bindings. Through a series of filters, we narrowed down these candidates to four SNPs. Then, we conducted a case-control study with 600 CRC patients and 638 controls in Han Chinese population.We observed that compared with A carriers (AA+AG), the GG genotype of rs12997:ACVR1 is associated with a significantly higher risk of CRC (OR=1.52, 95% confidence interval (95% CI)=1.04-2.21, P=0.031), particularly in nonsmokers with a higher OR of 1.63 (95%CI=1.04-2.55, P=0.032). Our study suggested that SNPs in miRNA target sites could contribute to the likelihood of CRC susceptibility and emphasized the important role of polymorphisms at miRNA-regulatory elements in carcinogenesis. © International Society of Oncology and BioMarkers (ISOBM) 2013.


Ke J.,Huazhong University of Science and Technology | Ke J.,State Key Laboratory of Environment Health Incubation | Lou J.,Huazhong University of Science and Technology | Lou J.,State Key Laboratory of Environment Health Incubation | And 23 more authors.
Oncotarget | Year: 2016

Genome-wide association studies (GWASs) have established chromosome 5q31.1 as a risk locus for colorectal cancer (CRC). We previously identified a potentially regulatory single nucleotide polymorphism (SNP) rs17716310 within 5q31.1. Now, we extended our study with another independent Chinese population, functional assays and analyses of TCGA (The Cancer Genome Atlas) data. Significant associations between rs17716310 and CRC risk were found in Present Study including 1075 CRC cases and 1999 controls (additive model: OR = 1.149, 95% CI = 1.027-1.286, P = 0.016), and in Combined Study including 1766 cases and 2708 controls (additive model: OR = 1.145, 95% CI = 1.045-1.254, P = 0.004). Dual luciferase reporter gene assays indicated that the variant C allele obviously increased transcriptional activity. Using TCGA datasets, we indicated rs17716310 as a cis expression quantitative trait locus (eQTL) for the gene SMAD5, whose expression was significantly higher in CRC tissues. These findings suggested that the functional polymorphism rs17716310 A > C might be a genetic modifier for CRC, promoting the expression of SMAD5 that belonged to the transforming growth factor beta (TGF-β) signaling pathway.


PubMed | State Key Laboratory of Environment Health Incubation
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2014

Evidence shows that single-nucleotide polymorphisms in microRNA (miRNA) target sites can create, destroy, or modify the miRNA/mRNA binding, therefore modulating gene expression and affecting cancer susceptibility. The transforming growth factor- (TGF-) signaling pathway plays a pivotal role in tumor initiation and progression. Intriguingly, recent advances of genome-wide association studies have identified multiple risk loci in this pathway to be associated with risk of colorectal cancer (CRC). To test the hypothesis that genetic variants in miRNA target sites in genes of the TGF- signaling pathway may also be associated with CRC risk, we first systematically scanned the single-nucleotide polymorphisms (SNPs) in genes of TGF- signaling pathway which potentially affect the miRNA/mRNA bindings. Through a series of filters, we narrowed down these candidates to four SNPs. Then, we conducted a case-control study with 600 CRC patients and 638 controls in Han Chinese population. We observed that compared with A carriers (AA+AG), the GG genotype of rs12997:ACVR1 is associated with a significantly higher risk of CRC (OR=1.52, 95% confidence interval (95% CI)=1.04-2.21, P=0.031), particularly in nonsmokers with a higher OR of 1.63 (95% CI=1.04-2.55, P=0.032). Our study suggested that SNPs in miRNA target sites could contribute to the likelihood of CRC susceptibility and emphasized the important role of polymorphisms at miRNA-regulatory elements in carcinogenesis.


PubMed | State Key Laboratory of Environment Health Incubation
Type: Journal Article | Journal: Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine | Year: 2014

Recent publications have found associations between single-nucleotide polymorphisms (SNPs) in 8q24 and the risk of breast cancer (BC) in some populations, but the conclusions are inconsistent. In order to further investigate the association between variants in this region and BC risk in Chinese population, we conducted an independent hospital-based case-control study to discern the effects of these SNPs on BC risk. We genotyped three 8q24 SNPs (rs13281615, rs6983267, and rs9642880) in 485 cases and 530 cancer-free controls. The results indicated that the rs13281615 G allele significantly increased BC risk, with an odds ratio (OR) of 1.23 (95% confidence interval (CI)=1.03-1.46) under the allelic model. Besides, stratification analysis reported that the significant association remained in the estrogen receptor (ER)+/progesterone receptor (PR)+ subgroup with a P value of 0.007 under the allelic model (OR=1.33, 95% CI=1.08-1.63). For the rs9642880 variant, only a feeble association was observed for the GT genotype compared with the GG genotype (OR=1.33, 95% CI=1.01-1.74). In addition, there was a negligible association between rs6983267 and BC risk in the ER-/PR- subgroup. However, no significant finding was observed in the overall participants. The findings suggested that polymorphisms in 8q24 may contribute to susceptibility to BC risk. However, functional studies are warranted to further elucidate the mechanisms of the association.

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