[Show abstract][Hide abstract] ABSTRACT: The association between endothelial nitric oxide synthase (eNOS) polymorphisms (intron 4a/b, -786T>C and 894G>T) and cancer risk remains elusive. In addition, no studies focused on their associations with the risk of breast cancer in Chinese Han population. Thus, a meta-analysis was conducted to determine the relationship between eNOS polymorphisms and cancer risk, and then a case-control study in Chinese Han population was performed to assess their associations with breast cancer susceptibility.Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association. The pooled analysis indicated that eNOS intron 4a/b and -786T>C polymorphisms were significantly associated with an increased risk of overall cancer. In subgroup analyses based on cancer type, the significant association was found between eNOS intron 4a/b polymorphism and prostate cancer risk, eNOS -786T>C polymorphism and risk of prostate, bladder and breast cancers, and eNOS 894G>T polymorphism and breast cancer risk. In subgroup analyses based on ethnicity, eNOS intron 4a/b and -786T>C polymorphisms were associated with an increased risk of cancer in Caucasians. In consistent with our meta-analysis results, a case-control study in Chinese Han population showed significant associations of eNOS -786T>C and 894G>T polymorphisms with the increased risk of breast cancer. In addition, stratified analyses based on pathological type showed that eNOS 894G>T polymorphism was only associated with the risk of infiltrative ductal carcinoma. Stratified analyses by tumor stage showed that eNOS -786T>C polymorphism was only associated with the risk of tumor stage III and IV.In conclusion, our meta-analysis and case-control study suggest that eNOS -786T>C and 894G>T polymorphisms are associated with the increased risk of breast cancer.
Medicine 07/2015; 94(26):e972. DOI:10.1097/MD.0000000000000972 · 4.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: TCF21 is known to function as a tumor suppressor and deregulated in several types of cancers; however, its role in breast cancer remains poorly understood. The aim of this study was to examine the expression of TCF21 messenger RNA (mRNA) in breast cancer and evaluate its clinical significance and biological role in tumor progression. TCF21 mRNA expression was analyzed in breast cancer cell lines and tissues by qRT-PCR. Overexpression approach was used to investigate the biological functions of TCF21 mRNA in breast cancer cell line (MDA-MB-231). A notably lower level of TCF21 mRNA expression was found in breast cancer cell lines and tissues. Furthermore, the low expression of TCF21 mRNA was associated with large tumor size and positive lymph node metastasis. Functional analysis showed that overexpression of TCF21 mRNA inhibited cell proliferation and epithelial-mesenchymal transition (EMT) of MDA-MB-231. In conclusion, our data provided the first evidence that TCF21 mRNA is significantly downregulated in breast cancer cell lines and tissues and regulates breast cancer cell proliferation and EMT. Thus, TCF21 may act as a potential therapeutic target for breast cancer intervention.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to investigate the association between a potentially functional polymorphism (rs153109, -964A > G) in the promoter region of interleukin-27 (IL-27) gene and the risk of papillary thyroid cancer (PTC) in a Chinese population. Genotype of IL-27 -964A > G polymorphism was determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum IL-27p28 levels were determined using enzyme-linked immunosorbent assay (ELISA). No significant difference was noticed in IL-27 -964A > G polymorphism between PTC patients and healthy controls in the overall analysis. However, analysis of clinical features showed that PTC patients carrying the GG genotype or G allele had significantly decreased risks for developing lymph node metastasis compared with those carrying the AA genotype or A allele (GG vs. AA: OR = 0.38, 95 % CI, 0.20-0.72; G vs. A: OR = 0.63, 95 % CI, 0.44-0.86). Furthermore, ELISA results demonstrated that serum IL-27p28 levels were significantly decreased in PTC patients compared with those in controls (P < 0.05). Serum IL-27p28 levels in healthy controls with the GG genotype were significantly high compared with those carrying AA genotype or the AG genotype (P < 0.05). In conclusion, our results suggest that IL-27 -964A > G polymorphism may be associated with the decreased risk for lymph node metastasis of PTC.
[Show abstract][Hide abstract] ABSTRACT: Tissue inhibitor of metalloproteinase-2 (TIMP-2) plays a critical role in human carcinogenesis. However, the association between TIMP-2 G-418C polymorphism and risk of cancer was reported with inconclusive results.
A meta-analysis of 11 published studies involving 2,658 cases and 3,433 controls was performed to assess the strength of association using odds ratios (ORs) with 95% confidence intervals (CIs).
The results indicated that no significant association between TIMP-2 G-418C polymorphism and cancer risk in overall population (GC vs. GG: OR = 1.26, 95% CI = 0.87-1.83; CC vs. GG: OR = 0.90, 95%CI = 0.50-1.63; GC/CC vs. GG: OR = 1.26, 95%CI = 0.87-1.82; C vs. G: OR = 1.19, 95%CI = 0.87-1.62). However, stratified analysis by ethnicity showed that TIMP-2 G-418C polymorphism was associated with cancer risk among Caucasian population (GC vs. GG: OR = 20.00, 95%CI = 9.90-40.38; GC/CC vs. GG: OR = 10.70, 95%CI = 1.11-103.20; C vs. G: OR = 14.98, 95%CI = 7.66-29.32) but not among Asian population.
This meta-analysis suggests that TIMP-2 G-418C polymorphism may not influence the susceptibility of total cancer in overall population, but it was associated with cancer risk among Caucasian population.
Journal of cancer research and therapeutics 04/2015; 11(2):308-12. DOI:10.4103/0973-1482.140961 · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growing evidence has indicated that lysyl oxidase (LOX) G473A polymorphism (rs1800449) is associated with cancer risk among Asians. However, results of single center and small sample study lack enough power. We first investigated the effect of LOX G473A polymorphism on cancer risk among Asians by a meta-analysis, and then further validated this association by a case-control study of colorectal cancer (CRC) with LOX G473A polymorphism in a Chinese population. STATA 12.0 software was used for the meta-analysis. The relationships were evaluated by calculating the pooled odds ratios (ORs) and their 95 % confidence intervals (CIs). In a case-control study comprising 577 CRC patients and 696 controls, LOX G473A polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Logistic regression was used to evaluate genetic associations with the occurrence of CRC. The results of our meta-analysis, including seven case-control studies with a total of 2,377 cancer patients and 2,499 controls, suggested that LOX G473A polymorphism might be associated with an increased risk of cancer among Asians. In addition, results of a case-control study indicated that individuals with the AA or AG genotype had a significantly increased susceptibility to CRC occurrence, compared with individuals who had GG genotype. Overall, this meta-analysis and case-control study of CRC observed convincing association of LOX G473A polymorphism with cancer risk in Asians; our study would contribute to complete elucidation of carcinogenesis.
[Show abstract][Hide abstract] ABSTRACT: Many studies have examined the association between CD28 T > C polymorphism (rs3116496) and cancer risk in various populations. However, results remained controversial. To assess this relationship more precisely, a meta-analysis was performed. A comprehensive literature search was performed using the PubMed database for relevant articles published (updated to January 1, 2014). Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to assess the strength of the association. A total of nine studies were selected for this meta-analysis, including 3,878 cases and 4,424 controls. The results indicated that CD28 T > C polymorphism (rs3116496) was not associated with the risk of cancer in overall population (CC + CT vs. TT, OR = 1.17, 95 %CI = 0.94–1.47, P
H = 0.00; CC vs. CT + TT, OR = 1.26, 95 %CI = 0.92–1.73, P
H = 0.86; CC vs. TT, OR = 1.27, 95 %CI = 0.92–1.74, P
H = 0.85; CT vs. TT, OR = 1.15, 95 %CI = 0.91–1.46, P
H = 0.00; and C vs. T, OR = 1.17, 95 %CI = 0.97–1.41, P
H = 0.00). In subgroup analysis according to cancer type, no significant association was found in cervical cancer or other cancer. However, in the subgroup analysis by ethnicity, the significant risk was found among Asians (CC + CT vs. TT, OR = 1.51, 95 %CI = 1.24–1.83, P
H = 0.05; C vs. T, OR = 1.46, 95 %CI = 1.22–1.74, P
H = 0.11), but not among Caucasians. The result of this meta-analysis suggested that CD28 T > C polymorphism (rs3116496) may have an increased risk of cancer in Asians.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Colorectal cancer (CRC) is the most common cancer worldwide. Both genetic and environmental factors play an important role in pathogenesis of CRC, susceptibility may be modified by functional polymorphisms in receptor tyrosine kinase genes, such as ErbB4. We here evaluated whether a 12-bp insertion/deletion (indel) polymorphism (rs6147150) in the 3'UTR of ErbB4 could potentially affect the occurrence of CRC in Chinese population. METHODS: We studied the genotypic and allelic frequencies of ErbB4 polymorphism in 399 patients with CRC and 419 control participants using polymerase chain reaction and polyacrylamide gel electrophoresis method. RESULTS: Under co-dominant model, we found that the del/del genotype of indel was associated with a significantly increased risk of CRC compared with its homozygote ins/ins (adjusted OR = 1.70, 95%CI = 1.06-2.71). Under recessive model, carrying of del/del genotype conferred a significantly increased risk for CRC compared with ins/ins and ins/del genotype (adjusted OR = 1.60, 95%CI = 1.03-2.50). Presence of 12-bp deletion allele of ErbB4 seemed to confer higher risk for CRC when compared with non-carriers (adjusted OR = 1.27, 95%CI = 1.02-1.57). Further stratification analysis showed that this association was more pronounced in patients with drinking. CONCLUSION: Our data suggested that individuals in Chinese population with the ErbB4 12-bp deletion allele may be at higher risk for CRC, rs6147150 would potentially be a promising novel biomarker for CRC susceptibility. Further validation of our results in larger populations and studies with functional assays are required.
Cancer biomarkers: section A of Disease markers 01/2014; 14(6):435-9. DOI:10.3233/CBM-140420 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Associations between cytotoxic T lymphocyte antigen-4 (CTLA-4) +49A/G polymorphism and cancer risk are inconclusive. We performed this meta-analysis to derive a more precise estimation of the relationship.
Cancer biomarkers: section A of Disease markers 01/2014; 14(4):287-94. DOI:10.3233/CBM-140403 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BRM (Brahma homologue) is well known for its critical role in tumor suppression and cancer development. Genetic variations in the promoter region of BRM have been suggested to be associated with loss of BRM expression and lung cancer risk. To the authors' knowledge, no study on the role of BRM genetic polymorphisms in hepatocellular carcinoma (HCC) risk has been performed.
In two independent case-control studies containing 796 HCC cases and 806 cancer-free individuals, we genotyped two putative functional insertion/deletion (indel) polymorphisms [BRM-1321 (rs3832613) and BRM-741 (rs34480940)] within promoter region of BRM in Chinese populations using a PCR-based method. Real-time RT-PCR analysis was used to explore the genotype-phenotype correlation between these polymorphisms and BRM expression in both tissue samples and HCC cell lines. Logistic regression analysis showed that compared to BRM-1321del/del genotype, the ins/del and ins/ins variant genotypes had an increased HCC risk [adjusted odds ratio (OR) = 1.47, 95% confidence interval (CI) = 1.19-1.82; adjusted OR = 2.55, 95% CI = 1.75-3.72, respectively]. No significant association between BRM-741 and HCC incidence was observed. However, stratification analysis revealed a significant association between ins/ins genotype of BRM-741 and increased HCC susceptibility in smokers (adjusted OR = 2.07, 95% CI = 1.33-3.22). Quantitative PCR analyses demonstrated that the genotypes of BRM-1321 and the corresponding haplotypes were significantly correlated with BRM expression in vivo. Compared with ins/ins genotype, subjects carrying ins/del and del/del genotype had 2.30 and 4.99 fold higher BRM expression in HCC tissue samples, respectively. Similar trends were observed in western blot analysis at protein level.
Our findings suggest that BRM promoter polymorphism (BRM-1321) could regulate BRM expression and may serve as a potential marker for genetic susceptibility to HCC.
PLoS ONE 01/2013; 8(1):e55169. DOI:10.1371/journal.pone.0055169 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PTEN, a candidate tumor suppressor gene, has been identified within chromosome 10q23 and plays an important role in tumorigenesis. The association between the IVS4 insertion/deletion (I/D) polymorphism of PTEN and cancer risk in several populations has been studied, but results are conflicting. The aim of the present study was to investigate association of PTEN IVS4 polymorphism with cancer risk by conducting a meta-analysis.
A literature search was conducted through PubMed, Chinese National Knowledge Infrastructure (CNKI) and WanFang databases (up to October 18, 2013). Six eligible studies with 2,179 cases and 3,132 controls were enrolled in the meta-analysis. The pooled odds ratio (OR) and 95% confidence intervals (CI) were used to assess the strength of association.
Our results indicated that the~polymorphism conferred a significantly decreased risk of overall cancer (dominant model: OR=0.87, 95% CI 0.77-0.99; recessive model: OR=0.83, 95% CI: 0.72-0.96; II vs. DD model: OR=0.79, 95% CI: 0.67-0.94; I vs. D model: OR=0.89, 95% CI: 0.82-0.97). Subgroup analysis by cancer type and ethnicity furtherly showed that PTEN gene IVS4 polymorphism was associated with decreased risk of digestive cancers (recessive model: OR=0.77, 95% CI: 0.64-0.92; II vs. DD model: OR=0.72, 95% CI: 0.58-0.91; I vs. D model: OR=0.84, 95% CI: 0.76-0.94), this strong association with reduced risk of cancer was also found in Asian population (recessive model: OR=0.83, 95% CI: 0.71-0.98; II vs. DD model: OR=0.79, 95% CI: 0.65-0.96; I vs. D model: OR=0.89, 95% CI: 0.81-0.98).
In conclusion, our meta-analysis suggested that PTEN IVS4 polymorphism might play a protective role in the development of cancer, further independent confirmation of associations observed in PTEN IVS4 polymorphism by more studies was necessary.
Cancer biomarkers: section A of Disease markers 01/2013; 13(6):465-70. DOI:10.3233/CBM-130386 · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The Prolyl hydroxylase 1 (EGLN2) is known to affect tumorigenesis by regulating the degradation of hypoxia-inducible factor (HIF). Polymorphisms in EGLN2 may facilitate cancer cell survival under hypoxic conditions and directly associate with cancer susceptibility. Here, we examined the contribution of a 4-bp insertion/deletion polymorphism (rs10680577) within the distal promoter of EGLN2 to the risk of hepatocelluar carcinoma (HCC) in Chinese populations. The contribution of rs10680577 to HCC risk was investigated in 623 HCC cases and 1242 controls and replicated in an independent case-control study consisting of 444 HCC cases and 450 controls. Logistic regression analysis showed that the deletion allele of rs10680577 was significantly associated with increased risk for HCC occurrence in both case-control studies (OR=1.40; 95%C.I.=1.18-1.66, P<0.0001; OR=1.49; 95%C.I.=1.18-1.88, P=0.0007). Such positive association was more pronounced in current smokers (OR=3.49, 95%C.I.=2.24-5.45) than non-smokers (OR=1.24, 95%C.I.=1.03-1.50) (heterogeneity P=0.0002). Genotype-phenotype correlation studies demonstrated that the deletion allele was significantly correlated with higher expression of both EGLN2 and RERT-lncRNA (a long non-coding RNA whose sequence overlaps with Ras-related GTP-binding protein 4b (RAB4B) and EGLN2) in vivo and in vitro. Furthermore, RERT-lncRNA expression was also significantly correlated with EGLN2 expression in vivo, consistent with in vitro gain-of-function study that showed overexpressing RERT-lncRNA up-regulated EGLN2. Finally, in-silico prediction suggested that the insertion allele could disrupt the structure of RERT-lncRNA. Taken together, our findings provided strong evidence for the hypothesis that rs10680577 contributes to hepatocarcinogenesis, possibly by affecting RERT-lncRNA structure and subsequently EGLN2 expression, making it a promising biomarker for early diagnosis of HCC.
Cancer Research 10/2012; 72(23). DOI:10.1158/0008-5472.CAN-12-0010 · 9.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) represents the most common primary malignancy of the liver with a worldwide increasing incidence. Although the risk factors for HCC are well characterized, the molecular mechanisms responsible for malignant transformation of hepatocytes are not well understood. In this study, a case-control study including 291 HCC patients and 294 healthy controls was conducted to investigate the association between HCC susceptibility and with a 4-bp insertion/deletion polymorphism (rs66465034) in the proximal promoter of CD3G. Logistic regression analysis showed that the heterozygote and the homozygote 4-bp ins/ins confer a significantly increased risk of HCC after controlling for other covariates (adjusted odds ratio [OR]=1.51, 95% confidence interval [C.I.] 1.01-2.27, p=0.040; OR=1.71, 95% C.I. 1.07-2.89, p=0.025, respectively). Carriage of the 4-bp insertion allele was associated with a greatly increased risk of developing the disease (OR=1.30, 95% C.I. 1.02-1.64, p=0.027). Moreover, hepatitis B virus (HBV) stratification analysis showed that the differences between cases and controls were more obvious in HBV-positive than in the HBV-negative population, suggesting a possible role of this polymorphism in the immune regulation during HBV infection. Further, luciferase-based transient transfection assays revealed that rs66465034 can affect promoter activity of CD3G, indicating its possible functional significance. Our data suggested that common genetic polymorphisms in CD3G may influence HCC risk in Chinese population. Considering the relative small sample size, replication in other populations with larger sample size and further functional analysis are required for fully understanding the roles of CD3G polymorphisms in predisposition for HCC.
DNA and cell biology 06/2012; 31(9):1480-5. DOI:10.1089/dna.2012.1706 · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogenesis of HCC is a multistage process with the involvement of genetic factors. The aim of the present study is to investigate the possible association between a 40-bp insertion/deletion polymorphism (indel) at constitutive promoter of MDM2 and risk of hepatocellular carcinoma (HCC) in a Chinese population. Using 420 HCC patients and 423 control subjects, we genotyped the indel polymorphism (rs3730485) using polymerase chain reaction method. Logistic regression was used to analyze the association between the polymorphism and HCC susceptibility. Under co-dominant model, we found that the ins/del and del/del genotype of indel was associated with a significantly increased risk of HCC compared with its homozygote ins/ins (OR=1.39, 95%C.I.=1.03-1.87; OR=1.68, 95%C.I.=1.03-2.73, respectively). Presence of 40-bp deletion allele of MDM2 seemed to confer higher risk for HCC when compared with non-carriers (OR=1.30, 95%C.I.=1.06-1.60, P=0.011). Further stratification analysis showed that this association was more pronounced in patients with a family history of HCC, early tumor stage and higher serum alpha-fetoprotein (AFP). These findings indicated that the MDM2 indel polymorphism may be a genetic modifier for developing HCC in Chinese population.
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. Although molecular biology of carcinogenesis and tumor progression of HCC has been increasingly understood with intense research in recent years, the molecular and cellular mechanisms of HCC pathogenesis are still poorly understood. In the present study, a case-control study including 390 HCC patients and 431 healthy controls was conducted to investigate the association of HCC susceptibility with the mitochondrial DNA (mtDNA) 9-bp deletion polymorphism in Chinese population. Chi-square testing showed that frequencies of 9-bp one repeat or two repeats were significantly different between HCC and control groups. Carriage of 9-bp one repeat fragment was associated with a significantly increased risk of developing HCC (odds ratio=1.48, 95% confidence interval: 1.03-2.14, p=0.027). Stratification analysis further showed that the differences between cases and controls were more obvious in drinkers than nondrinkers. Computational modeling of the 9-bp deletion polymorphism suggests that the mtDNA sequence without the 9-bp deletion polymorphism lies within a predicted binding site (seed region) for hsa-miR-519c-5p and hsa-miR-526a. Our data suggested that the 9-bp deletion polymorphism in mitochondria may influence HCC risk, likely through specific microRNA-mediated regulation, which was possibly involved in the pathogenesis of HCC. The replication of our studies in other populations with larger sample size is warranted.
[Show abstract][Hide abstract] ABSTRACT: The 14-bp insertion/deletion (indel) polymorphism located in the 3' UTR of the human leukocyte antigen-G (HLA-G) gene plays a role in several autoimmune and chronic inflammatory diseases. HLA-G expression is associated with hepatocellular carcinoma (HCC) prognosis, especially in early stage, with high expression independently associated with shortened overall survival and increased tumor recurrence. In the present study, we carried out a case-control study in a Chinese population (318 cases and 599 controls) to estimate the susceptibility to HCC associated with the 14-bp indel polymorphism. Logistic regression analysis showed that the heterozygote and the homozygote 14-bp ins/ins confer a lower risk of HCC (adjusted OR = 0.75, 95% CI: 0.57-1.01, p = 0.061; OR = 0.54, 95% CI: 0.30-0.98, p = 0.031, respectively). Hepatitis B virus (HBV) stratification analysis showed that the associations were stronger in the HBV-positive population. Immunohistochemical analysis further showed that HLA-G expression in HCC tissues with 14-bp del/del genotype was more prominent than for heterozygous and 14-bp ins/ins genotype (p < 0.01). Taken together, our results suggested that the HLA-G 14-bp indel polymorphism may be a marker for genetic susceptibility to HCC in Chinese populations. Further studies from different populations with larger sample size are warranted to validate our findings.
DNA and cell biology 05/2011; 30(12):1027-32. DOI:10.1089/dna.2011.1238 · 1.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Hepatocellular carcinoma (HCC) is one of the most common and severe diseases in the world. Besides the influence of environmental factors, such as viral infection, an increasing number of novel genetic components identified by genome-wide association studies have been associated with predisposition to HCC. Thus, studies focusing on functional variants in these findings are indispensable. In the present study, based on in-silico analysis, we carried out a case-control study in a Chinese population (207 cases and 245 controls) to investigate the association between HCC susceptibility with a 7 base pair (bp) insertion/deletion polymorphism (rs3917) in the 3'UTR of COL1A2. Our results showed that the ins/del + del/del genotype had an odds ratio of 1.76 (95% C.I.=1.03-3.01; P=0.028) for developing HCC compared to the ins/ins genotype. Carriers for the "del" allele of rs3917 were associated with a 1.73-fold increased risk for HCC (95% C.I.=1.06-2.84; P(trend)=0.02). Computational modeling suggests that this polymorphism is located in the hsa-let-7 g potential target sequence in the COL1A2 3' untranslated region. Our data suggest that most likely, common genetic changes in COL1A2 may influence HCC risk, at least in part by let-7 g-mediated regulation, which is possibly involved in the pathogenesis of HCC. The replication of our studies in other populations will further strengthen our understanding of this association.
Cancer Genetics 05/2011; 204(5):265-9. DOI:10.1016/j.cancergen.2011.03.007 · 2.42 Impact Factor