CDC20 May Serve as a Potential Biomarker-Based Risk Score System in Predicting the Prognosis of Patients with Hepatocellular Carcinoma.

Background: The specificity and sensitivity of hepatocellular carcinoma (HCC) diagnostic markers are limited, hindering the early diagnosis and treatment of HCC patients. Therefore, improving prognostic biomarkers for patients with HCC is urgently needed. Methods: HCC-related datasets were downloaded from the public databases. Differentially expressed genes (DEGs) between HCC and adjacent nontumor liver tissues were then identified. Moreover, the intersection of DEGs in four datasets (GSE138178, GSE77509, GSE84006, and TCGA) was used in the functional enrichment, and module genes were obtained by a coexpression network. Cox and Kaplan-Meier analyses were used to identify overall survival- (OS-) related genes from module genes. Area under the curve (AUC) > 0.9 of OS-related genes was then carried out in order to perform the protein-protein interaction network. The feature genes were identified by least absolute shrinkage and selection operator (LASSO). Furthermore, the hub gene was identified through the univariate Cox model, after which the correlation analysis between the hub gene and pathways was explored. Finally, infiltration in immune cell types in HCC was analyzed. Results: A total of 2,227 upregulated genes and 1,501 downregulated DEGs were obtained in all four datasets, which were mainly found to be involved in the cell cycle and retinol metabolism. Accordingly, 998 OS-related genes were screened to construct the LASSO model. Finally, 8 feature genes (BUB1, CCNB1, CCNB2, CCNA2, AURKB, CDC20, OIP5, and TTK) were obtained. CDC20 was shown to serve as a poor prognostic gene in HCC and was mainly involved in the cell cycle. Moreover, a positive correlation was noted between the high degree of infiltration with Th2 and CDC20. Conclusion: High expression of CDC20 predicted poor survival, as potential target in the treatment for HCC.

CD54+ rabbit adipose-derived stem cells overexpressing HIF-1α facilitate vascularized fat flap regeneration.

Fat flap transplantation is frequently performed in patients suffering from soft tissue defects resulting from disease or trauma. This study explored the feasibility of constructing vascularized fat flaps using rabbit adipose-derived stem cells (rASCs) and collagen scaffolds in a rabbit model. We evaluated rASCs proliferation, paracrine function, adipogenesis, vascularization, and CD54 expression, with or without HIF-1α transfection in vitro and in vivo. We observed that adipogenic differentiation potential was greater in rASCs with high CD54 expression (CD54+rASCs) than in those with low expression (CD54-rASCs), both in vitro and in vivo. HIF-1α overexpression not only augmented this effect, but also enhanced cell proliferation and paracrine function in vitro. We also demonstrated that HIF-1α-transfected CD54+rASCs showed enhanced paracrine function and adipogenic capacity, and that paracrine function increases expression of angiogenesis-related markers. Thus, CD54+rASCs overexpressing HIF-1α enhanced large volume vascularized fat flap regeneration in rabbits, suggesting CD54 may be an ideal candidate marker for ASCs adipogenic differentiation.

Ginsenoside Rg1 and platelet-rich fibrin enhance human breast adipose-derived stem cell function for soft tissue regeneration.

Adipose-derived stem cells (ASCs) can be used to repair soft tissue defects, wounds, burns, and scars and to regenerate various damaged tissues. The cell differentiation capacity of ASCs is crucial for engineered adipose tissue regeneration in reconstructive and plastic surgery. We previously reported that ginsenoside Rg1 (G-Rg1 or Rg1) promotes proliferation and differentiation of ASCs in vitro and in vivio. Here we show that both G-Rg1 and platelet-rich fibrin (PRF) improve the proliferation, differentiation, and soft tissue regeneration capacity of human breast adipose-derived stem cells (HBASCs) on collagen type I sponge scaffolds in vitro and in vivo. Three months after transplantation, tissue wet weight, adipocyte number, intracellular lipid, microvessel density, and gene and protein expression of VEGF, HIF-1α, and PPARγ were higher in both G-Rg1- and PRF-treated HBASCs than in control grafts. More extensive new adipose tissue formation was evident after treatment with G-Rg1 or PRF. In summary, G-Rg1 and/or PRF co-administration improves the function of HBASCs for soft tissue regeneration engineering.

Type conversion of secretomes in a 3D TAM2 and HCC cell co-culture system and functional importance of CXCL2 in HCC.

Macrophages play important roles in the tumor microenvironment, driving cancer progression and metastasis, particularly in hepatocellular carcinoma (HCC). However, few studies have assessed the exact secretome composition in HCC. In the present study, the impact of different phenotype of macrophages on HCC cells was investigated. Alternatively activated macrophages (M2) were found to significantly increase the proliferation, migration, and invasion abilities of SMMC7721 cells (all P < 0.05). M2 were then co-cultured with SMMC7721 cells to reconstruct the tumor microenvironment. Conditioned medium from 3D single cultures of M2, SMMC7721 cells, and their co-culture system were analyzed using quantitative proteomics via iTRAQ labeling combined with mass spectrometric analysis. Secretome analysis revealed a total of 159 differential secreted proteins in the co-culture system compared to the single culture systems, with 63 being up-regulated (>1.3-fold) and 96 down-regulated (<0.7-fold). CXCL2 was confirmed to have higher expression in the co-culture system and HCC tissues, and was selected for further investigation. Functional effects data suggested that recombinant human CXCL2 significantly enhanced the migration, invasion ability of SMMC7721 cells, and weakened adhesion ability. While CXCL2 neutralization and CXCR2 blockage significantly inhibited the effects of CXCL2 on SMMC7721 cells, indicating that CXCL2 may play pivotal role in HCC metastasis.

Glutathione S-transferase gene GSTM1, gene-gene interaction, and gastric cancer susceptibility: evidence from an updated meta-analysis.

BACKGROUND: The null genotype of GSTM1 have been implicated in gastric cancer risk, but numerous individual studies showed mixed, or even conflicting results. Thus, a meta-analysis was performed. RESULTS: We identified 54 individual studies involving 9,322 cases and 15,118 controls through computer-based searches of PubMed, Embase, and Cochrane Library. It was found that the null genotype of GSTM1 was associated with an increased gastric cancer risk (OR = 1.207, 95% CI: 1.106-1.317, P < 0.001), under the random-effects model (I(2) : 49.9%, PQ <0.001). From stratification analyses for ethnicity, alcohol drinking, Helicobacter pylori infection, an effect modification of gastric cancer risk was found in the subgroups of ethnicity, smoking status, Helicobacter pylori infection, whereas null result was found in the subgroups of alcohol drinking. We also undertook gene-gene interaction analysis between GSTM1 and GSTT1 genes for gastric cancer risk, and the results indicated that the dual null genotypes of GSTM1 and GSTT1 might elevate the risk of gastric cancer (OR = 1.505, 95% CI: 1.165-1.944, P = 002). CONCLUSIONS: This meta-analysis suggests that the null genotype of GSTM1 may be a important genetic risk factor for gastric cancer development.

Interleukin-12B+1188A/C polymorphism contributes to increased hepatocellular carcinoma susceptibility: evidence from a meta-analysis.

BACKGROUND: Interleukin-12 (IL-12) is a multifunctional cytokine that induces interferon (IFN)-γ secretion and plays an important role in antitumor immunity. The IL-12B +1188A/C polymorphism was found to correlate with a decreased cytokine production and/or activity, which may lead to increased susceptibility to cancers including hepatocellular carcinoma (HCC). Previous epidemiological studies investigating the association between IL-12B +1188A/C polymorphism and HCC risk reported inconsistent results. We performed a meta-analysis to derive a precise estimation of the association. METHODS: All studies published up to July 2014 on the association between IL-12B +1188A/C polymorphism and HCC risk were identified by searching electronic databases including PubMed, Embase, Cochrane library, and Chinese Biomedical Literature database (CBM). Data were extracted by two independent authors and the odds ratios (ORs) together with corresponding 95% confidence intervals (CIs) were used to assess the association between IL-12B +1188A/C polymorphism and HCC risk. RESULTS: Five studies with 1864 cases and 2077 controls were included in the meta-analysis. We observed that the IL-12B +1188A/C polymorphism was significantly correlated with increased HCC risk when all studies were pooled into the meta-analysis (CC vs. AA: OR=1.306, 95% CI 1.063-1.606, P=0.011; AC vs. AA: OR=1.193, 95% CI 1.014-1.405, P=0.034; CC+AC vs. AA: OR=1.260, 95% CI 1.098-1.445, P=0.001). In subgroup analyses by ethnicity, source of control, and study quality, significant increased HCC risk was found in Asians, hospital-based studies, and high quality studies. CONCLUSIONS: The present meta-analysis suggests that the IL-12B+1188A/C polymorphism is a low-penetrant risk factor for HCC development, especially among Asians. Further large and well-designed studies are needed to confirm this association.

The association of common functional polymorphisms in mir-146a and mir-196a2 and hepatocellular carcinoma risk: evidence from a meta-analysis.

MicroRNAs (miRNAs) are small non-coding RNA molecules that function as tumor suppressors or oncogenes. Single nucleotide polymorphisms (SNPs) located in the miRNAs influence the function of mature miRNAs and may contribute to cancer development. Studies investigating the association between miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. We performed a meta-analysis of all available studies to summarize this situation. Eligible studies were identified by search of electronic databases including PubMed, Embase, and Cochrane library for the period up to August 2014. The association of miR-146a rs2910164 and miR-196a2 rs11614913 polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 12 studies with 4171 cases and 4901 controls were included for miR-146a rs2910164 polymorphism and 10 studies with 4687 cases and 4990 controls were available for miR-196a2 rs11614913 polymorphism. With respect to miR-146a rs2910164 polymorphism, statistical significant increased HCC risk was found when all studies were pooled into the meta-analysis (GG+CG vs CC: OR = 1.097, 95% CI 1.005-1.197, P = 0.037). In subgroup analyses by ethnicity, source of control, and HWE in controls, significant increase of HCC risk was found in Asians, population-based studies, and studies consistent with HWE, but not in Caucasians, hospital-based studies, and studies inconsistent with HWE. With respect to miR-196a2 rs11614913 polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the miR-146a rs2910164 polymorphism contributes to increased HCC susceptibility, especially in Asian populations. Further large and well-designed studies are required to validate this association.

Association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma risk: a systematic review and meta-analysis.

Genetic polymorphisms of xeroderma pigmentosum group D (XPD) in the nucleotide excision repair pathway may influence cancer susceptibility by affecting the capacity for DNA repair. Studies investigating the association between XPD Lys751Gln and Asp312Asn polymorphisms and hepatocellular carcinoma (HCC) risk reported inconsistent results. The aim of this study was to quantitatively summarize the evidence for such an association. Eligible studies were identified by searching electronic databases including PubMed, Embase, Cochrane library, and CBM, Chinese Biomedical Literature Database, for the period up to October 2014. The association of XPD Lys751Gln and Asp312Asn polymorphisms and HCC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). Finally, a total of 11 studies with 4322 cases and 4970 controls were included for XPD Lys751Gln polymorphism and 6 studies with 2223 cases and 2441 controls were available for XPD Asp312Asn polymorphism. With respect to XPD Lys751Gln polymorphism, statistically significant increased HCC risk was found when all studies were pooled into the meta-analysis (Gln/Gln vs Lys/Lys: OR = 1.363, 95% CI 1.065-1.744, P = 0.014; Lys/Gln vs Lys/Lys: OR = 1.205, 95% CI 1.099-1.321, P = 0.000; Gln/Gln+Lys/Gln vs Lys/Lys: OR = 1.300, 95% CI 1.141-1.480, P = 0.000). In subgroup analyses by ethnicity, source of control, Hardy-Weinberg equilibrium (HWE) in controls, hepatitis B virus (HBV) infection, and statistically significant increase of HCC risk was found in East Asians, population-based studies, studies consistent with HWE, and HBV-positive subjects, but not in mixed/other populations, hospital-based studies, studies deviating from HWE, and HBV-negative subjects. With respect to XPD Asp312Asn polymorphism, no significant association with HCC risk was found in the overall and subgroup analyses. The results suggest that the XPD Lys751Gln polymorphism contributes to increased HCC susceptibility, especially in East Asian populations. Further, large and well-designed studies are required to validate this association.

Association of single nucleotide polymorphisms in VDR and DBP genes with HBV-related hepatocellular carcinoma risk in a Chinese population.

BACKGROUND: Polymorphisms of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (DBP) have been widely investigated because of the complex role played by vitamin D in cancer tumorogenesis. In this study, we investigated the association between VDR and DBP gene polymorphisms and HBV-related HCC risk in a Chinese population. METHODS: Study subjects were divided into three groups: 184 HBV patients with HCC, 296 HBV patients without HCC, and 180 healthy controls. The VDR rs2228570, and rs3782905 and the DBP rs7041 polymorphisms were genotyped using PCR-RFLP and the VDR rs11568820 polymorphism was genotyped by PCR-SSP, respectively. DNA sequencing was performed to validate the genotype results. RESULTS: We found that there were significant differences in the genotype and allele frequencies of the VDR rs2228570 and DBP rs7041 polymorphisms between HBV patients with HCC and healthy controls. The rs2228570 T allele was associated with a significant increased HBV-related HCC risk as compared with the C allele. The rs2228570 TT and TT/TC genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type CC homozygote. Similarly, the rs7041 G allele was associated with a significant increased HBV-related HCC risk as compared with the T allele. The rs7041 GG and GG/TG genotypes were correlated with a significant increased HBV-related HCC risk when compared with the wild-type TT homozygote. However, we did not observe any significant effect of VDR rs11568820, and rs3782905 polymorphisms on HBV-related HCC risk in this population. In haplotype analysis, we also did not find any significant differences in haplotype frequencies of the VDR gene between HBV patients with HCC and the healthy controls. CONCLUSIONS: We conclude that the VDR rs2228570 and DBP rs7041 polymorphisms may contribute to increased susceptibility to HBV-related HCC in the Chinese population. Due to the marginal significance, further large and well-designed studies in diverse ethnic populations are needed to confirm our results.

Role of IL-4 gene polymorphisms in HBV-related hepatocellular carcinoma in a Chinese population.

BACKGROUND: Interleukin-4 (IL-4) is best known as an important mediator and modulator of immune and inflammatory responses. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer, and genetic variations in the IL-4 gene may be associated with the risk of hepatitis B virus (HBV)-related HCC. However, few studies have been conducted on their association. OBJECTIVES: To clarify the effects of IL-4 gene polymorphisms on the risk of HBV-related HCC, two common variants, -590C/T (rs2243250) and -33C/T (rs2070874), and their relationship with HBV-related disease risk were investigated in a Chinese population. METHODS: IL-4 -590C/T and -33C/T polymorphisms were examined in 154 patients with HBV-related HCC, 62 patients with HBV-induced liver cirrhosis (LC), 129 patients with chronic hepatitis B (CHB), and 94 healthy controls, using the polymerase chain reaction-restriction fragment length polymorphism method and DNA sequencing. RESULTS: Overall, no significant differences were observed regarding the IL-4 -590C/T and -33C/T polymorphism genotypes, alleles, or haplotypes between the patient groups and the healthy controls. However, the CC genotypes of IL-4 -590C/T and -33C/T polymorphisms were observed to be significantly associated with CHB in subgroup analysis in males [CC versus TT (OR: 4.193, 95% CI: 1.094-16.071, P = 0.037; and OR: 3.438, 95% CI: 1.032-11.458, P = 0.044) and CC versus TT+CT (OR: 4.09, 95% CI: 1.08-15.49, P = 0.038; and OR: 3.43, 95% CI: 1.04-11.28, P = 0.042)]. CONCLUSIONS: These findings suggest that genetic variants in IL-4 -590C/T and -33C/T polymorphisms may be a risk factor for CHB in Chinese males but not for HBV-related LC or HCC.

Impact of caspase-8 (CASP8) -652 6N del and D302H polymorphisms on prostate cancer in different ethnic groups.

BACKGROUND: Despite evidence suggesting roles for caspase-8 (CASP8) -652 6N del and D302H polymorphisms in prostate cancer (PCa), the association of these polymorphisms with PCa risk remains inconclusive. Therefore, a meta-analysis was performed to more precisely estimate the association of CASP8 -652 6N del and D302H polymorphisms with PCa susceptibility. MATERIALS AND METHODS: A comprehensive literature search was conducted to identify all case-control studies of CASP8 D302H and -652 6N del polymorphisms and PCa risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association and the precision of the estimate, respectively. RESULTS: Nine -625 6N del studies and 4 D302H studies were included. CASP8 -652 6N del and D302H polymorphisms were not significantly associated with PCa risk in the overall analyses. However, in the subgroup analysis stratified by ethnicity, -625 6N del was significantly associated with PCa risk in the East Asian and Indian populations under the recessive model. Furthermore, the subgroup analysis strongly suggested that D302H was associated with lower PCa risk in the Non-Indian population under the dominant model. CONCLUSIONS: In our meta-analysis, ethnic-specific differences were evident in the association of CASP8 -625 6N del and D302H polymorphisms with PCa risk.

Association of IL-2 polymorphisms and IL-2 serum levels with susceptibility to HBV-related hepatocellular carcinoma in a Chinese Zhuang population.

BACKGROUND AND OBJECTIVE: Interleukin-2 (IL-2) is an immunoregulatory cytokine produced by T cells and plays an important role in antitumor immunity. Variations in the DNA sequence of the IL-2 gene may lead to altered cytokine production and/or activity, and thus modulate an individual's susceptibility to hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). To test this hypothesis, we investigated whether IL-2 gene polymorphisms and its serum levels are associated with HBV-related HCC in a Chinese population. METHODS: The +114T/G and -384T/G polymorphisms in the IL-2 gene were examined in 115 cases of chronic hepatitis B (CHB), 67 cases of HBV-related liver cirrhosis (LC), 107 cases of HBV-related HCC, and 105 healthy controls by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing. The serum IL-2 levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: We found that there were significant differences in the genotype and allele frequencies of the IL-2 gene +114T/G polymorphism between the HBV-related HCC patients and the healthy controls. The +114 TG and GG genotypes were associated with a significant increased HCC risk as compared with the TT genotype (OR=1.988, 95% CI, 1.034-3.480, P=0.009 for TG genotype, and OR=1.975, 95% CI, 1.012-3.341, P=0.013 for GG genotype, respectively). The +114 G allele was correlated with a significant increased HCC risk as compared with the T allele (OR=1.423, 95% CI, 1.023-1.975, P=0.031). In addition, we found significant decreased serum IL-2 in HBV-related HCC patients (288.6±177.1ng/L) compared with healthy controls (238.2±136.7ng/L) (t=2.32, P=0.021). Genotypes carrying the +114 G variant allele were associated with decreased serum IL-2 levels compared with the homozygous wild-type genotype in HBV-related HCC patients. CONCLUSION: The results suggested that the IL-2 +114T/G polymorphism may contribute to increased HBV-related HCC risk through regulating the serum IL-2 levels. Further large and well-designed studies in diverse ethnic populations are needed to confirm our results.

Establishing reference values for blood urea nitrogen and serum creatinine in Chinese Han ethnic adult men.

BACKGROUND: The aim was to calculate the two-sided 95th percentile reference values for blood urea nitrogen (BUN) and serum creatinine (SCr) in Chinese Han ethnic adult men. METHODS: Serum samples were collected from Chinese Han ethnic adult men aged 20 - 69 years. After screening based on the inclusion and exclusion criteria, a total of 1575 individuals were enrolled in our study. BUN and SCr values were measured on an automatic analyzer (Dade Behring, USA). The data was analyzed and calculated using nonparametric statistical methods. RESULTS: BUN and SCr values were not normally distributed. The reference values were in the range 3.3 - 7.5 mmol/L for BUN and 64 - 113 micromol/L for SCr. BUN levels were significantly lower in the smoking group than the non-smoking group (Z = -4.52, p < 10(-5)). An increase with age was observed in BUN levels (r(s) = 0.172, p < 0(-5)) and lower SCr levels were weakly associated with the older subjects (r(s) = -0.071, p = 0.005). Moreover, it was found that higher Body Mass Index (BMI) tended toward higher levels of SCr (r(s) = 0.118, p < 10(-5)). CONCLUSIONS: The reference values established for BUN and SCr exhibit a slight deviation compared to those developed in previous studies. We propose reference values of BUN for smokers and non-smokers be constructed, and age- and BMI-specific reference values be applied in clinical laboratories.

Reference interval for osteocalcin in Chinese Han ethnic males from the Fangchenggang Area Male Health and Examination Survey.

BACKGROUND: The aim of this study was to set a reference interval (RI) for osteocalcin (OC) in a healthy Han male population from the Fangchenggang Area Male Health and Examination Survey (FAMHES) project and study the effects of age, BMI, smoking, and alcohol consumption. METHODS: We used data from 2018 Han ethnic males who participated in FAMHES project from September 2009 to December 2009. Serum OC values were measured by electrochemiluminescence immunoassay on COBAS 6000 system E601 (Elecsys module) immunoassay analyzers. RESULTS: OC data does not have a normal distribution or Gaussian pattern (Z = 3.791, p < 0.001). After log-transformation, data took on a normal, Gaussian distribution (Z = 0.968, p = 0.306). The RI of serum OC was 12.49 - 43.94 ng/mL. No difference in OC concentration was noted either between non-smoker or smoker groups (p = 0.629) or non-drinker and drinker groups (p = 0.748). OC levels varied with age (r = -0.371, p < 0.001) and BMI (r = -0.331, p < 0.001), and the age-dependent and BMI-dependent RIs were calculated. CONCLUSIONS: The RIs for serum OC exhibit slight differences compared to previously reported reference ranges. Age-dependent and BMI-dependent RIs for serum OC should be implemented in clinical laboratories.

C-reactive protein genetic polymorphisms increase susceptibility to HBV-related hepatocellular carcinoma in a Chinese population.

Chronic inflammation has been implicated in the etiology of hepatocellular carcinoma (HCC). The C-reactive protein (CRP) genetic polymorphisms affected serum CRP concentrations and elevation of CRP has been considered as the hallmark of acute and chronic inflammation. In this study, we investigated the association between CRP genetic polymorphisms and HBV-related HCC risk in a Chinese population. Two polymorphisms in the CRP gene (rs3093059 and rs2794521) were examined in 192 HBV-related HCC patients, 277 non-HCC patients with HBV infection, and 192 healthy controls using polymerase chain reaction-restriction fragment length polymorphism method. DNA direct sequencing was performed to validate the results of genotyping. We found that there were significant differences in the genotype and allele frequencies of the CRP gene rs3093059 polymorphism between the HBV-related HCC patients and the non-HCC patients with HBV infection. The rs3093059 TC genotype was associated with a significant increased HCC risk as compared with the TT genotype (odds ratio (OR) = 1.98, 95 % confidence interval (CI) 1.32-2.95, P = 0.001). The rs3093059 C allele was correlated with a significant increased HCC risk as compared with the T allele (OR = 1.65, 95 % CI 1.16-2.30, P = 0.005). Furthermore, the rs3093059 TC combined with CC genotypes were found to correlate with a significant increased HCC risk compared with the TT genotype in dominant model (OR = 1.92, 95 % CI 1.29-2.82, P = 0.001). However, we did not find any significant effect of CRP rs2794521 polymorphism on HCC risk in this population. In haplotype analysis between HBV-related HCC patients and non-HCC patients with HBV infection, the TC haplotype was found correlated with a significant increased HCC risk (OR = 1.750, 95 % CI 1.234-2.480, P = 0.001). The results suggested that the CRP rs3093059 polymorphism may contribute to increased HCC risk in HBV-infected patients in the Chinese population. Further large and well-designed studies in diverse ethnic populations are needed to confirm our results.

Association of PvuII and XbaI polymorphisms in estrogen receptor alpha gene with the risk of hepatitis B virus infection in the Guangxi Zhuang population.

BACKGROUND AND OBJECTIVE: Available evidence has suggested that estrogen receptor alpha (ESR1) is implicated in the pathogenic process of hepatitis B infection. Therefore, we evaluated the association of PvuII (rs2234693) and XbaI (rs9340799) in ESR1 and HBV infection in Guangxi Zhuang populations. METHODS: A total of 389 subjects were divided into four groups: 112 patients with chronic hepatitis B (CHB), 65 patients with hepatitis B virus (HBV)-related liver cirrhosis (LC), 107 patients with HBV-related hepatocellular carcinoma (HCC), and 105 healthy controls. The polymerase chain reaction-restriction fragment length polymorphism strategy was used to detect ESR1 gene PvuII and XbaI polymorphisms. RESULTS: Compared with healthy controls, binary logistic regression analyses show that the CC genotype of PvuII was associated with a significantly increased susceptibility to CHB compared with the TT genotype (OR=1.760, 95% CI 1.316-2.831; p=0.044). The PvuII CC genotype was also associated with significantly increased risk of HBV-related LC (OR=1.921, 95% CI 1.342-2.478; p=0.043). Similarly, the subjects bearing the homozygous CC genotype of PvuII polymorphism also had more than a 1.7-fold increased risk for development of HCC (OR=1.748, 95% CI 1.313-2.787; p=0.010) compared with those bearing the TT genotype. Furthermore, the AC haplotype was associated with a significantly increased risk of HCC with an OR of 1.456 (p=0.003). In contrast, there were no significant differences in the genotype and allele of XbaI polymorphisms in the ESR1 gene between the groups of patients and healthy controls. In addition, ESR1 polymorphisms were not significantly associated with susceptibility to HBV-related HCC when using CHB and LC patients as references. CONCLUSION: We conclude that the CC genotype of PvuII in ESR1 is associated with an increased risk of CHB, HBV-related LC and HCC in Guangxi Zhuang populations.

Association of CYP1B1 Leu432Val polymorphism and lung cancer risk: an updated meta-analysis.

BACKGROUND: Cytochrome P4501B1 (CYP1B1) a phase I enzyme, is involved in the activation of a broad spectrum of procarcinogens. Impacts on the catalytic activity of the CYP1B1 enzyme, as well as an association of the Leu432Val polymorphism with the risk of lung cancer, have been described; however, the results remain controversial. METHODS: We conducted a meta-analysis of all available studies to clarify the effects of the Leu432Val polymorphism on lung cancer risks basing on 2,543 lung cancer cases and 3,304 controls from ten separate comparisons. We also performed subgroup analyses by ethnicity (categorized as Caucasian, Asian and African-American), gender, smoking status ,and histological type. A pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to estimate the strength of the association. RESULTS: A significantly increased risk was found in our meta-analysis in the overall population (Val/Val vs. Leu/Leu: OR = 1.371, 95% CI 1.137-1.652, P = 0.001). In subgroup analysis, significant associations with lung cancer susceptibility were also found in Caucasians (Val/Val vs. Leu/Leu: OR = 1.312, 95% CI 1.075-1.602, P = 0.008), females (Val/Val vs. Leu/Leu: OR = 1.472, 95% CI 1.097-1.976, P = 0.010), and smokers (dominant model Leu/Val + Val/Val vs. Leu/Leu: OR = 1.257, 95% CI 1.016-1.554, P = 0.035). Null results were noted in the subgroup analysis by histological type under different genetic models. CONCLUSIONS: Our results suggest that the CYP1B1 Leu432Val polymorphism acts as a risk factor for the carcinogenesis of lung cancer.

Positive association between IL-16 rs11556218 T/G polymorphism and cancer risk: a meta-analysis.

BACKGROUND: Interleukin-16 (IL-16) is a multifunctional cytokine which plays a key role in inflammatory and autoimmune diseases as well as in cancer. Genetic polymorphisms of IL-16 have been implicated in susceptibility to cancer. However, associations remain inconclusive. The present meta-analysis was therefore carried out to establish a more conclusive association of IL-16 polymorphisms with cancer risk. MATERIALS AND METHODS: Relevant studies were searched through the PubMed, Embase, Web of Science, Google Scholar and Wan fang electronic databases updated in October 2013. Odds ratios (OR) and 95% confidence intervals (95% CI) were used to assess the association between IL-16 polymorphisms and cancer risk. RESULTS: Eight eligible studies (rs4778889 T/C: 8, rs11556218 T/G: 7, rs4072111 C/T: 6) that met our selection criteria were included. The meta-analysis indicated that rs11556218 T/G was associated with a significant increased risk of cancer (G vs. T, OR=1.321, 95% CI=1.142-1.528, P <0.001; TG vs. TT, OR=1.665, 95% CI=1.448-1.915, P<0.001; GG+TG vs. TT, OR=1.622, 95% CI=1.416-1.858, P<0.001),as well as nasopharyngeal carcinoma and colorectal cancer. Furthermore, in the subgroup of Chinese, significant associations were found between rs11556218 polymorphism and cancer risk. There was no statistically significant association between the other two variants (rs4778889, rs4072111) and risk of cancer. CONCLUSIONS: This meta-analysis suggests that the IL-16 rs11556218 polymorphism is associated with increased cancer risk. Large well-designed studies involving various cancer types and different populations are now needed.

XPC Lys939Gln polymorphism contributes to colorectal cancer susceptibility: evidence from a meta-analysis.

BACKGROUND: Published studies investigating the association between XPC Lys939Gln polymorphism and colorectal cancer (CRC) risk reported inconclusive results. We performed a meta-analysis to derive a precise estimation of the relationship. METHODS: A comprehensive literature search was done in databases PubMed, EMBASE, and Cochrane library up to December 2013. The association between XPC Lys939Gln polymorphism and CRC risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Eight studies with 3,301 cases and 4,177 controls were included in the meta-analysis. We observed that the XPC Lys939Gln polymorphism was correlated with an increased CRC risk when all studies were pooled into the meta-analysis (Gln/lys vs. Lys/Lys: OR = 1.293, 95% CI 1.169-1.430, P = 0.000; Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.260, 95% CI 1.145-1.388, P = 0.000). In stratified analyses by ethnicity, smoking, and study quality, significant increased CRC risk was found in Asians (Gln/lys vs. Lys/Lys: OR = 1.345, 95% CI 1.187-1.523, P = 0.000; Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.317, 95% CI 1.170-1.484, P = 0.000), nonsmokers (Gln/Gln + Gln/lys vs. Lys/Lys: OR = 1.286, 95% CI 1.020-1.622, P = 0.033), and high quality studies. In subgroup analysis by source of control, significant increased CRC risk was found in both hospital-based studies and population-based studies. However, in subgroup analysis according to cancer location, no any significant association was detected. CONCLUSIONS: This meta-analysis suggests that the XPC is a candidate gene for CRC susceptibility. The XPC Lys939Gln polymorphism may play an important role in CRC development among Asians and nonsmokers. Further large and well-designed studies are needed to confirm this association. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1665902729125948.

Association between OGG1 Ser326Cys and APEX1 Asp148Glu polymorphisms and breast cancer risk: a meta-analysis.

BACKGROUND: The base excision repair (BER) pathway removes DNA damage caused by ionizing radiation, reactive oxidative species and methylating agents. OGG1 and APE1 are two important genes in the BER pathway. Many epidemiological studies have evaluated the association between polymorphisms in the two BER genes (OGG1 Ser326Cys and APE1 Asp148Glu) and breast cancer risk. However, the results are inconsistent. METHODS: We searched the electronic databases including PubMed, Embase and Cochrane library for all eligible studies for the period up to February 2014. Data were extracted by two independent authors and pooled odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were used to assess the strength of the association. RESULTS: A total of 17 studies including 9,040 cases and 10,042 controls were available for OGG1 Ser326Cys polymorphism and 7 studies containing 2,979 cases and 3,111 controls were included for APE1 Asp148Glu polymorphism. With respect to OGG1 Ser326Cys polymorphism, we did not find a significant association with breast cancer risk when all eligible studies were pooled into the meta-analysis. However, in subgroup analyses by ethnicity and menopausal status, statistical significant increased breast cancer risk was found in Asian populations (Cys/Cys vs. Ser/Ser: OR=1.157, 95% CI 1.013-1.321, P=0.011; Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.113, 95% CI 1.009-1.227, P=0.014) and postmenopausal patients (Cys/Cys vs. Ser/Cys+Ser/Ser: OR=1.162, 95% CI 1.003-1.346, P=0.024). In subgroup analysis according to quality score, source of control, and HWE in controls, no any significant association was detected. With respect to APE1 Asp148Glu polymorphism, no significant association with breast cancer risk was demonstrated in the overall and stratified analyses. CONCLUSIONS: The present meta-analysis suggests that the OGG1 Ser326Cys polymorphism may be a risk factor for breast cancer in Asians and postmenopausal patients. Further large and well-designed studies are needed to confirm this association. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1156934297124915.