The association between TNFR gene polymorphisms and the risk of Hepatitis B Virus-Related Liver Diseases in Chinese population.

Tumor necrosis factor receptor superfamily 2 (TNFR2) plays an important role in controlling the progression of antiviral and antitumorr. Evidence suggests that TNFR2 is involved in the pathogenesis of HBV-induced liver injury. We therefore examined whether TNFR2 polymorphisms are associated with the risk of HBV-related liver disease in Chinese population. In this case-control study, 115 chronic hepatitis B (CHB) patients, 86 HBV-related liver cirrhosis patients (LC), 272 HBV-related hepatocellular carcinoma patients (HCC) and 269 healthy controls were recruited. TNFR2 rs1061622 and rs1061624 polymorphisms were examined using a polymerase chain reaction-restriction fragment length polymorphism analysis. Binary logistic regression analyses revealed that the A allele of rs1061624 was positively associated with the risk of CHB (AA vs. GG, P = 0.026; AA vs. GA+GG, P = 0.021), LC (AA vs. GG, P = 0.027; AA+GA vs. GG, P = 0.036), and HCC (GA vs. GG, P = 0.046; GA+AA vs. GG, P = 0.031). Moreover, subgroup analysis indicated that male subjects have increased risk in developing CHB and LC. Nevertheless, no association was found between rs1061622 polymorphism and HBV-related liver diseases in the overall or subgroup analyses. Our retrospective study suggests that the TNFR2 rs1061624 polymorphism is associated with HBV-related CHB, LC, and HCC in Chinese population, particularly in males.

Impact of Storage Time on Hepatitis B Virus DNA Stability in Clinical Specimens Determined by Quantitative Real-time PCR.

BACKGROUND: Detecting blood levels of hepatitis B virus (HBV) DNA must be accurate and credible. Shipment and storage conditions of clinical samples affect the quality of nucleic acids and can interfere with HBV DNA analysis. The aim of our study was to compare HBV DNA stability in plasma specimens at 4 degrees C for different storage periods. METHODS: Blood samples from 30 hepatitis B surface antigen (HBsAg) positive patients were collected in tubes containing EDTA-K2. Each sample was divided into eight aliquots, one of which was measured immediately for the initial viral load. The remaining aliquots were then stored at 4 degrees C and assessed after 1, 2, 3, 7, 14, 21, and 30 days of storage. Quantification of HBV DNA was performed by real-time polymerase chain reaction (RT-PCR), and the difference in HBV DNA concentrations between two different time points was analysed with a paired-samples t-test. RESULTS: HBV DNA was measured in a range of 2.00 - 8.00 IU/mL, with low within-run and between-run coefficients of variation (< 10%). Storing plasma for one month at 4 degrees C revealed no significant decrease in HBV DNA level (p = 0.231), and no trend was evident to indicate continued reduction over a 3-week storage period. CONCLUSIONS: Based on the results of this study, storing plasma for up to one month at 4 degrees C does not affect the stability of HBV DNA, regardless of the initial viral load.

Reference Intervals for Alpha-Fetoprotein (AFP) and Carcinoembryonic Antigen (CEA) in Guangxi Zhuang Ethnic Males from the FAMHES Project.

BACKGROUND: Several studies have reported the reference intervals of serum AFP and CEA levels in ethnically diverse populations, but there is a lack of such reference data among Zhuang ethnic males. The aim of this study was to establish the locally validated reference intervals for AFP and CEA in the male population of the Guangxi Zhuang ethnic group. METHODS: A total of 283 Zhuang ethnic males, aged 22 to 69 years, were included from the Fangchenggang Area Male Health and Examination Survey (FAMHES) project database. The one-sided upper 95th-percentile limit was used to estimate the reference intervals for serum AFP and CEA. RESULTS: The total non-parametric reference intervals for Zhuang ethnic males were < 4.95 IU/mL (1 IU/mL is equal to 1.21 ng/mL) and < 5.12 ng/mL for AFP and CEA, respectively. Correlation analysis in this study showed AFP and CEA levels were significantly associated with increasing age, whereas no BMI related differences were found after adjustment for age. CONCLUSIONS: The present reference intervals for serum AFP and CEA values deviated from that reported in previous studies. Age-specific reference intervals should be performed in clinical laboratories to obtain more precise estimations for the clinical conditions of young adults and elderly people.

p53 Arg72Pro polymorphism confers the susceptibility to endometriosis among Asian and Caucasian populations.

PURPOSE: Findings from studies on the association between the p53 Arg72Pro polymorphism and endometriosis susceptibility have so far been inconsistent. Therefore, we undertook a meta-analysis to clarify the association of p53 Arg72Pro polymorphism with the risk of endometriosis. METHODS: Relevant studies were chosen by searching PubMed, Embase, the Cochrane Library databases, CNKI, Wanfang database, and CBM for articles published before and up to April 30, 2015. Two independent reviewers performed the eligibility evaluation and data extraction. The odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated for the overall risk estimate. RESULTS: Eleven case-control studies involving 1834 endometriosis cases and 2331 controls were included. Pooled data analysis suggested that the p53 72Pro variant is a significant endometriosis risk factors in comparison to the 72Arg variant (Pro vs. Arg: OR = 1.298, 95 % CI 1.082-1.558; Pro/Pro vs. Arg/Arg: OR = 1.751, 95 % CI 1.130-2.711; Pro/Arg vs. Arg/Arg: OR = 1.530, 95 % CI 1.174-1.994), which was strengthened in the dominant model (Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 1.570, 95 % CI = 1.181-2.087). In the stratified analysis by ethnicity and Hardy-Weinberg equilibrium (HWE) in the controls, we found strong associations in Asians and in studies that were consistent with HWE. However, the analyses of the revised American Fertility Society (rAFS) stage and the menopausal status subgroup did not reveal any significant associations. CONCLUSION: In conclusion, the p53 Arg72Pro polymorphism was closely related to the risk of endometriosis, especially in Asian populations.

PIN1 genetic polymorphisms and the susceptibility of HBV-related hepatocellular carcinoma in a Guangxi population.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (PIN1) plays a critical role in different signaling pathways, cell cycle progression and proliferation, and gene expression, and it has been found to overexpress in many tumor tissues. Recently, researchers have found that PIN1 gene polymorphisms may alter the function of protein and be associated with the risk of cancer. The present study analyzed three common polymorphisms in promoter regions (rs2233678 and rs2233679) and in exon2 (rs2233682) of the PIN1 gene in 254 patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) and 235 healthy controls in a Guangxi study population to determine whether any relationship exists between the polymorphisms and the risk of HBV-related HCC. The results revealed that the rs2233679 TT genotype was associated with increased risk of HCC with HBV infection [odds ratio (OR) = 2.04, 95 % confidence interval (95 % CI) = 1.13-3.69, p = 0.019]. This association was stronger in men than in women (OR = 2.17, 95 % CI = 1.09-4.34, p = 0.028) as well as in men 50 years of age and older (OR = 3.91, 95 % CI = 1.29-11.80, p = 0.016); moreover, for alcohol drinkers, being a carrier of the PIN1 rs2233679 CT genotype had a moderately increased risk of HCC (OR = 3.98, 95 % CI = 1.02-15.57, p = 0.047). In contrast, people carrying the rs2233682 GA genotype and A alleles were 0.23 times more likely to develop HCC (OR = 0.23, 95 % CI = 0.06-0.87, p = 0.031 and OR = 0.23, 95 % CI = 0.06-0.87, p = 0.030). No such associations were found in the PIN1 rs2233678 polymorphisms between the HBV-related HCC cases and the controls. In addition, the haplotype GCA was found to be a high protection factor for HCC with HBV infection (OR = 0.14, 95 % CI = 0.03-0.62, p = 0.003). In conclusion, this study's findings suggest that the PIN1 rs2233679 TT genotype, the rs2233682GA genotype, and A alleles might be associated with the HBV-related HCC in a Guangxi study population.

Association of Paraoxonase 1 Gene Polymorphisms With the Risk of Hepatitis B Virus-related Liver Diseases in a Guangxi Population: A Case-control Study.

Paraoxonase 1 (PON1), a liver-induced glycoprotein enzyme responsible for antioxidant defense against reactive oxygen species and anti-inflammatory, has been linked to various cancers. The objective of this study was to explore the association of PON1 rs662 and rs705382 with the risk of chronic hepatitis B (CHB), hepatitis B virus-related liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in patients living in the Guangxi region of southern China. The PON1 rs662 and rs705382 single-nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 99 CHB patients, 84 LC patients, 258 HCC patients, and 221 healthy controls.Significant associations with CHB risk were observed for the rs705382 SNP after adjusting for sex, age, ethnicity, smoking, alcohol consumption, and body mass index. When stratified by sex and age, this positive association was significantly strengthened among men and individuals over 40 years old. Moreover, a decreased risk of LC was associated with the rs705382 CG and the combined GG + CG genotypes among women, with borderline statistical significance. In haplotype analyses, the haplotype GA was associated with a 1.68-fold increase in the risk of HCC.Our results showed that the PON1 rs705382 SNP might be a risk factor for CHB in Guangxi populations.

Genetic polymorphisms of C-reactive protein increase susceptibility to HBV-related hepatocellular carcinoma in a Guangxi male population.

C-reactive protein (CRP) is a biomarker of inflammation and the production has been shown to be influenced by genetic variation in CRP gene. HBV-related hepatocellular carcinoma (HCC) is a typical inflammation-related disease occurs mainly in men. The present study was designed to investigate the association between CRP polymorphisms and HBV-related HCC risk in a Chinese male population. The CRP rs2794521 and rs3093059 SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) in 158 HBV patients with HCC, 207 HBV patients without HCC, and 150 unrelated healthy controls. A significant increased HCC risk in HBV patients were observed for the rs3093059 SNP comparing with those without HCC (C allele vs. T allele: adjusted OR=1.56, 95% CI, 1.07-2.29, P=0.021; TC vs. TT: adjusted OR=1.77, 95% CI, 1.13-2.76, P=0.012; TC/CC vs. TT: adjusted OR=1.76, 95% CI, 1.14-2.71, P=0.011). However, we did not observe any significant association of rs3093059 polymorphism with HCC when compared with healthy controls. With respect to rs2794521 polymorphism, no significant associations of this polymorphism with HCC risk were found in this population. In haplotype analysis between HBV patients with HCC and HBV patients without HCC, the TC haplotype was found correlated with a significant increased HCC risk (OR=1.803, 95% CI, 1.237-2.335, P<0.001). We concluded that the CRP rs3093059 polymorphism may play a significant role in the development of HBV-related HCC in the Guangxi male population.

The MTHFR C677T polymorphism contributes to increased risk of Alzheimer's disease: evidence based on 40 case-control studies.

The association between methylenetetrahydrofolate reductase (MTHFR) gene C677T polymorphism and Alzheimer's Disease (AD) risk has been widely reported with inconsistent results. We performed an updated meta-analysis of all available studies to clarify this situation. We conducted a comprehensive literature search in PubMed Alzgene, Embase, and Chinese Biomedical Literature database (CBM) for the period up to June 2014. Finally, a total of 40 case-control studies with 4503 AD cases and 5767 controls were included. Overall, significant increased AD risk was found, when all studies were pooled into the meta-analysis. In subgroup analyses stratified by ethnicity, age of onset, and APOE ϵ4 status, significant increased AD risk was found in Asians, late-onset AD, and APOE ϵ4 carriers, but not in Caucasians, early-onset AD, and non-APOE ϵ4 carriers. The present meta-analysis suggested that the MTHFR is a candidate gene for AD susceptibility. The MTHFR C677T polymorphism may be a risk factor for AD in Asians, APOE ϵ4 carriers, and late-onset AD. Further, investigations taking the potential gene-gene and gene-environmental interactions into consideration for the MTHFR C677T polymorphism should be conducted.

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.

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.

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 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.

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.

The NQO1 Pro187Ser polymorphism and breast cancer susceptibility: evidence from an updated meta-analysis.

BACKGROUND NAD(P)H: quinone oxidoreductase 1 (NQO1) plays a central role in catalyzing the two-electron reduction of quinoid compounds into hydroquinones. The NQO1 Pro187Ser polymorphism was found to correlate with a lower enzymatic activity, which may result in increased incidence of carcinomas including breast cancer. Previous studies investigating the association between NQO1 Pro187Ser polymorphism and breast cancer risk showed inconsistent results. We performed a meta-analysis to summarize the possible association. METHODS: All studies published from January 1966 to February 2014 on the association between NQO1 Pro187Ser polymorphism and breast cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between NQO1 Pro187Ser polymorphism and breast cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Ten studies with 2,773 cases and 4,076 controls were finally included in the meta-analysis. We did not observe a significant association between NQO1 Pro187Ser polymorphism and breast cancer risk when all studies were pooled into the meta-analysis. In subgroup analysis by ethnicity, significant increased breast cancer risk was found in Caucasians (Ser/Pro vs. Pro/Pro: OR=1.145, 95% CI=1.008-1.301, P=0.038; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.177, 95% CI=1.041-1.331, P=0.009). When stratified by source of control, significant increased breast cancer risk was found in population-based studies (Ser/Pro vs. Pro/Pro: OR=1.180, 95% CI=1.035-1.344, P=0.013; Ser/Ser+Ser/Pro vs. Pro/Pro: OR=1.191, 95% CI=1.050-1.350, P=0.007). However, in subgroup analyses according to menopausal status, quality score, and HWE in controls, no any significant association was detected. CONCLUSIONS: Our meta-analysis provides the evidence that the NQO1 Pro187Ser polymorphism contributed to the breast cancer susceptibility among Caucasians. 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/1248639991252504.

Current evidences on XPC polymorphisms and gastric cancer susceptibility: a meta-analysis.

BACKGROUND: Reduced DNA repair capacities due to inherited polymorphisms may increase the susceptibility to cancers including gastric cancer. Previous studies investigating the association between Xeroderma Pigmentosum group C (XPC) gene polymorphisms and gastric cancer risk reported inconsistent results. We performed a meta-analysis to summarize the possible association. METHODS: All studies published up to January 2014 on the association between XPC polymorphisms and gastric cancer risk were identified by searching electronic databases PubMed, EMBASE, Cochrane library, and Chinese Biomedical Literature database (CBM). The association between XPC polymorphisms and gastric cancer risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs). RESULTS: Six studies with 1,355 gastric cancer cases and 2,573 controls were finally included in the meta-analysis. With respect to Lys939Gln polymorphism, we did not observe a significant association when all studies were pooled into the meta-analysis. When stratified by ethnicity, source of control, and study quality, statistical significant association was not detected in all subgroups. With respect to Ala499Val and PAT-/+polymorphisms, we also did not observe any significant association with gastric cancer risk in the pooled analysis. CONCLUSIONS: This meta-analysis based on current evidences suggested that the XPC polymorphisms (Lys939Gln, Val499Arg, and PAT-/+) did not contribute to gastric cancer risk. Considering the limited sample size and ethnicity included in the meta-analysis, further larger scaled and well-designed studies are needed to confirm our results. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1485880312555069.