The Role of the rs1544410 Polymorphism of Vitamin D Receptor Gene in Breast Cancer Susceptibility

This study was devised to investigate the genetic effect modification of the BsmI polymorphism associated with the susceptibility to breast cancer. Case–control studies of the BsmI polymorphism and breast cancer were searched. A total of 17 eligible publications were included in our final analysis. Pooled ORs and 95 % CIs were obtained by means of fixed effects model. The general and stratified analyses according to ethnicity showed that the association between the BsmI polymorphism and the risk of breast cancer was not statistically significant. However, the subgroup of the hospital-based studies was found to confer protection against the disease (OR_BBvs.bb = 0.83, 95 % CI = 0.71–0.97, P _h = 0.571; OR_BBvs.Bb+bb = 0.86, 95 % CI = 0.74–1.00, P _h = 0.903; OR_{allele B vs. allele b} = 0.92, 95 % CI = 0.86–0.99, P _h = 0.337). Our results suggested that the presence of the BsmI polymorphism may contribute to the susceptibility of breast cancer. It is necessary that future large-scale studies should be conducted to further confirm the association between the BsmI polymorphism and breast cancer risk.     

The l58Val/Met polymorphism of catechol-O-methyl transferase gene and prostate cancer risk: a meta-analysis

The association between COMT Val158Met polymorphism and prostate cancer has been evaluated. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the relationship, a meta-analysis was performed. A comprehensive search was conducted to identify the eligible studies of COMT Val158Met polymorphism and prostate cancer risk. Summary odds ratios (OR) and 95 % confidence interval (CI) for COMT Val158Met polymorphism and prostate cancer were calculated. Statistical analysis was performed with the software program Review Manage (Version 5.0) and Stata (Version 12.0). Six case–control studies, totally 4,118 persons including 2,143 cases and 1,975 controls, met the included criteria and thus were selected. Our analysis suggested that Val158Met polymorphism was associated with prostate cancer risk in overall population. Collectively, the results of the present study suggest that significant associations of COMT Val158Met polymorphisms with prostate cancer were observed (for additive model: OR = 1.068, 95 % CI = 1.002–1.138, P _{heterogeneity} = 0.363, P = 0.043; for dominant model: OR = 1.266, 95 % CI = 1.057–1.517, P _{heterogeneity} = 0.000, P = 0.011; for recessive model: OR = 1.050, 95 % CI = 0.961–1.146, P _{heterogeneity} = 0.558, P = 0.279; and Val allele versus Met allele OR = 0.932, 95 % CI = 0.894–0.971, P _{heterogeneity} = 0.272, P = 0.001). In the subgroup analysis, we detected no significant association between the COMT 158 Val/Met genotype and prostate cancer risk in Caucasian and Asian populations, while the contrary result for additive model (OR = 2.43, 95 % CI = 1.08–5.43, P _{heterogeneity} = 0.04, P = 0.03) in Asian populations. The result of this meta-analysis suggests that COMT l58Val/Met polymorphism might be contributed to the overall prostate cancer risk.     

Pre-mir-27a rs895819 polymorphism and cancer risk: a meta-analysis

Aberrant expression of miRNAs plays critical roles in cancer development. Single nucleotide polymorphism (SNP) in miRNA precursors may affect miRNA expression levels. An important SNP in the pre-mir-27a with a A to G change (rs895819) was identified. Several original studies have explored the role of this SNP in cancer risk, but the results of these studies remain conflicting rather than conclusive. Therefore, we performed a meta-analysis of the published studies to derive a more precise estimation of the association between pre-mir-27a rs895819 polymorphism and cancer risk. In this meta-analysis, a total of 6 case–control studies (including 3,255 cases and 4,181 controls) were analyzed. The results of the overall meta-analysis did not suggest any associations between pre-mir-27a rs895819 polymorphism and cancer susceptibility. However, an decreased risk was observed in the subgroup of breast cancer patients (G vs A: OR = 0.90, 95 % CI = 0.83 ~ 0.97; P _{heterogeneity}  = 0.75) or in the subgroup of Caucasian race (G vs A: OR = 0.90, 95 % CI = 0.83 ~ 0.97, P _{heterogeneity}  = 0.78, I ² = 0; AG vs AA: OR = 0.84, 95 % CI = 0.75 ~ 0.94, P _{heterogeneity}  = 0.35, I ² = 3.7 %; GG+AG vs AA: OR = 0.85, 95 % CI = 0.76 ~ 0.94, P _{heterogeneity}  = 0.48, I ² = 0). The findings suggest that pre-mir-27a rs895819 polymorphism may have some relation to breast cancer susceptibility or cancer development in Caucasian.     

Association of CDKN1B gene polymorphisms with susceptibility to breast cancer: a meta-analysis

A number of case–control studies have been conducted to investigate the association of CDKN1B gene polymorphisms with breast cancer. However, these studies reported conflicting results. The aim of our study was to quantitatively summarize the association of CDKN1B gene polymorphisms with breast cancer. Systemic searches of the PubMed, Excerpta Medica Database, and Chinese Biomedical Literature Database databases were performed, with the last report up to Oct 2012. Odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of the association. Seven studies including 6,822 cases and 7,186 controls were involved in this meta-analysis, which was performed for two CDKN1B gene polymorphisms (rs2066827 and rs34330). Significant association was found for rs34330 polymorphism (T versus C: OR = 1.10, 95 % CI = 1.03–1.18, P = 0.003; CT + TT versus CC: OR = 1.38, 95 % CI = 0.98–1.93, P = 0.07; TT versus CC + CT: OR = 1.06, 95 % CI = 0.93–1.21, P = 0.38; TT versus CC: OR = 1.23, 95 % CI = 1.04–1.45, P = 0.02; CT versus CC: OR = 1.42, 95 % CI = 0.97–2.09, P = 0.07), but not for rs2066827 polymorphism (G versus T: OR = 0.99, 95 % CI = 0.91–1.08, P = 0.84; TG + GG versus TT: OR = 0.98, 95 % CI = 0.89–1.08, P = 0.69; GG versus TT + TG: OR = 1.04, 95 % CI = 0.83–1.30, P = 0.75; GG versus TT: OR = 1.03, 95 % CI = 0.82–1.30, P = 0.77; TG versus TT: OR = 0.97, 95 % CI = 0.88–1.08, P = 0.58). This meta-analysis suggests that breast cancer may be associated with CDKN1B gene rs34330 polymorphism, but not rs2066827 polymorphism.     

The association between C-159T polymorphism in CD14 gene and susceptibility to tuberculosis: a meta-analysis

The association between CD14 gene C-159T polymorphism and tuberculosis (TB) susceptibility remains inconclusive. To derive a more precise estimation of the correlation, we performed a meta-analysis summarize the possible at a systematic manner. PubMed, HighWire and ScienceDirect databases covering all papers (up to November 2012) were searched. Statistical analyses were conducted by Rev-Man and STATA. Random- and fixed-effect models were used to estimate pooled odds ratios (ORs) and 95 % confidence intervals (CIs), based on between-study heterogeneity. Eight published case–control studies investigating the relationship between C-159T polymorphism in CD14 gene and TB susceptibility were included. Results showed that individuals with T allele have an increased risk of TB compared with those with C allele (OR (95 % CI) was 1.52 (1.11, 2.08) for TT vs. TC + CC, P < 0.001; 1.27 (1.01, 1.61) for T vs. C, P = 0.04). When stratified by ethnicity, variant TT homozygote carriers had an 86 % increased risk of TB in Asians (OR (95 % CI) was 1.86 (1.57, 2.20) for TT vs. TC + CC, P < 0.001), but not in Caucasians (OR (95 % CI) was TT vs. TC + CC: OR = 0.78, 95 % CI = 0.51–1.21, P = 0.61). This meta-analysis suggests that C-159T polymorphism in CD14 gene is associated with increased risk of TB, especially in Asians, but not in Caucasians.     

STK15 rs2273535 polymorphism and cancer risk: A meta-analysis of 74,896 subjects

Background: It has been suggested that the serine/threonine kinase 15 (STK15) T91A rs2273535 polymorphism is associated with susceptibility to cancer. However, the results are conflicting. We performed this meta-analysis to derive a more precise estimation of the relationship. Methods: PubMed was searched to select studies. Case–control studies containing available genotype frequencies of the STK15 rs2273535 polymorphism were chosen, and the odds ratio (OR) with its 95% confidence interval (CI) was utilized to assess the strength of association. Results: 52 studies – including 34,057 cases and 40,839 controls – were identified. A significant effect of the STK15 rs2273535 polymorphism on cancer risk was found (AA vs. TT: OR = 1.13, 95%CI = 1.01–1.26, P_{heterogeneity} < 0.001; AA vs. TA/TT: OR = 1.12, 95%CI = 1.02–1.22, P_{heterogeneity} < 0.001; TA/AA vs. TT: OR = 1.06, 95%CI = 1.01–1.12, P_{heterogeneity} < 0.001). Stratified analysis by cancer type revealed that the STK rs2273535 polymorphism may contribute to the risk of breast cancer (AA vs. TT: OR = 1.21, 95%CI = 1.01–1.44, P_{heterogeneity} = 0.002), colorectal cancer (AA vs. TA/TT: OR = 1.24, 95%CI = 1.05–1.47, P_{heterogeneity} = 0.124), and esophageal cancer (AA vs. TA/TT: OR = 1.19, 95%CI = 1.02–1.39, P_{heterogeneity} = 0.148). Further subgroup analysis by ethnicity indicated that there was a statistically increased cancer risk in Asians (AA vs. TA/TT: OR = 1.20, 95%CI = 1.05–1.37, P_{heterogeneity} = 0.004). Conclusion: This meta-analysis suggests that the STK15 rs2273535 polymorphism is a candidate gene polymorphism for cancer susceptibility, especially in Asian populations.     

CYP1A1 MspI polymorphism is associated with prostate cancer susceptibility: evidence from a meta-analysis

Cytochrome P450 1A1 (CYP1A1), an important phase I xenobiotic metabolizing enzyme, is responsible for metabolizing numerous carcinogens, particularly polycyclic aromatic hydrocarbons. The genetic polymorphism of CYP1A1 at the site of MspI (CYP1A1 MspI) has been implicated in prostate cancer risk, but the results of individual studies remain conflicting and inconclusive. The aim of this meta-analysis was to investigate the association of CYP1A1 MspI polymorphism with prostate cancer risk more precisely. We performed a comprehensive search of the PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases from their inception up to September 20, 2012 for relevant publications. The pooled odds ratios with the corresponding 95 % confidence intervals (95 % CIs) were calculated to assess the association of CYP1A1 MspI polymorphism with prostate cancer risk. In addition, stratified analyses by ethnicity and sensitivity analyses were conducted for further estimation. Sixteen eligible publications with 6,411 subjects were finally included into the meta-analysis after checking the retrieved papers. Overall, meta-analysis of total studies suggested that individuals carrying the TC genotype and a combined C genotype (CC + TC) were more susceptible to prostate cancer (OR_{TC vs. TT} = 1.33, 95 % CI 1.10–1.61, P _OR = 0.004; OR_{CC+TC vs. TT} = 1.27, 95 % CI 1.05–1.55, P _OR = 0.016). Stratified analysis of high quality studies also confirmed the significant association (OR_{TC vs. TT} = 1.32, 95 % CI 1.04–1.67, P _OR = 0.024; OR_{CC+TC vs. TT} = 1.30, 95 % CI 1.02–1.66, P _OR = 0.035). In subgroup analyses by ethnicity, a significant association between the CYP1A1 MspI polymorphism and risk of prostate cancer was found among Asians (OR_{TC vs. TT} = 1.44, 95 % CI 1.20–1.72, P _OR < 0.001; OR_{CC+TC vs. TT} = 1.33, 95 % CI 1.12–1.58, P _OR = 0.001), but not in Caucasians or mixed populations. The meta-analysis suggests an important role of the CYP1A1 MspI polymorphism in the risk of developing prostate cancer, especially in Asians.     

Association of TGF-β1 +869C/T promoter polymorphism with susceptibility to autoimmune diseases: a meta-analysis

Many case–control studies have investigated the role of TGF-β1 gene +869C/T promoter polymorphism in autoimmune diseases, but the results are inconsistent. To clarify this point, we performed a meta-analysis based on all available studies in Pubmed, Elsevier Science Direct, Google Searching, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure. Crude odds ratios (ORs) with 95 % confidence intervals were calculated to estimate the strength of the association. A fixed or random effects model was used on the basis of heterogeneity. A total of 21 papers including 2,693 cases and 3,036 controls were considered in the current meta-analysis. These studies encompass two ankylosing spondylitis (AS), eight rheumatoid arthritis (RA), four systemic lupus erythematosus (SLE), and seven systemic sclerosis (SSc). The results showed that TGF-β1 +869C/T promoter polymorphism were associated with susceptibility to RA (CC vs. TT: OR = 0.65, 95 % CI = 0.48–0.88, P = 0.005; CC vs. CT + TT: OR = 0.56, 95 % CI = 0.45–0.69, P = 0.000; C vs. T: OR = 0.81, 95 % CI = 0.71–0.93, P = 0.003). When stratified by race, significant association was observed only in Asian population. However, we failed to reveal the association between this gene promoter polymorphism and AS, SLE, and SSc. Therefore, this meta-analysis suggests a possible association between TGF-β1 +869C/T promoter polymorphism and RA, especially in Asian population.     

Association between polymorphism in TRAF1/C5 gene and risk of rheumatoid arthritis: a meta-analysis

Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disease. Single nucleotide polymorphisms of tumor necrosis factor-receptor associated factor 1/complement component 5 (TRAF1/C5) gene are suspected to be associated with the risk of RA. This meta-analysis was performed to study the relationship between the polymorphism rs10818488 in TRAF1/C5 gene with RA. We retrieved the relevant articles from PubMed, EMBASE and the China National Knowledge Infrastructure databases. Odd ratios were calculated to assess the association between TRAF1/C5 rs10818488 polymorphism and RA risk. Meta-analyses were performed on the total data set and separately for the major ethnic groups and RF and ACAP status. All analyses were performed using the Stata software. Eight articles were included in the present analysis. Meta-analysis showed a weak association between TRAF1/C5 rs10818488 polymorphism and RA in all subjects (OR = 1.13, 95 % CI = 1.01–1.27, P _{heterogeneity} < 0.001). Stratified analyses indicated that the TRAF1/C5 rs10818488 A allele was significantly associated with RA in Caucasians (OR = 1.29, 95 %CI = 1.14–1.47, P _{heterogeneity} = 0.026), Asians (OR = 0.92, 95 %CI = 0.86–0.99, P _{heterogeneity} = 0.378) and Africans (OR = 1.56, 95 %CI = 1.23–1.98, P _{heterogeneity} = 0.876), also significantly in positive ACPA and positive RF patients versus controls (ORs were 1.20 and 1.25, 95 %CIs were 1.08–1.33 and 1.14–1.37, P values for heterogeneity were 0.215 and 0.133, respectively). Genetic polymorphism rs10818488 in TRAF1/C5 gene might be associated with RA susceptibility.     

Relationships between PON1 Q192R polymorphism and clinical outcome of antiplatelet treatment after percutaneous coronary intervention: a meta-analysis

This meta-analysis was performed to assess the relationships between the PON1 Q192R (rs662 T>C) polymorphism and the clinical outcome of antiplatelet treatment after percutaneous coronary intervention (PCI). A range of electronic databases were searched: Web of Science (1945–2013), the Cochrane Library Database (Issue 12, 2013), PubMed (1966–2013), EMBASE (1980–2013), CINAHL (1982–2013) and the Chinese Biomedical Database (CBM) (1982–2013) without language restrictions. Meta-analysis was conducted using the STATA 12.0 software. The crude odds ratio (OR) with their 95 % confidence interval (CI) were calculated. Six clinical cohort studies with a total number of 5,189 patients undergoing PCI for coronary heart disease were included. Our meta-analysis revealed that the PON1 Q192R polymorphism was correlated with an increased risk of major adverse cardiovascular events (MACE) in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.22, 95 % CI 1.04–1.43, P = 0.014; CT+CC vs. TT: OR = 1.38, 95 % CI 1.03–1.86, P = 0.029; CC vs. TT: OR = 1.45, 95 % CI 1.05–1.99, P = 0.024; respectively), especially among Asians. Furthermore, we found significantly positive correlations between the PON1 Q192R polymorphism and the incidence of stent thrombosis in patients receiving antiplatelet treatment after PCI (C allele vs. T allele: OR = 1.42, 95 % CI 1.08–1.87, P = 0.011; CT+CC vs. TT: OR = 1.93, 95 % CI 1.01–3.67, P = 0.046; CC vs. TT: OR = 2.18, 95 % CI 1.09–4.35, P = 0.027; respectively). Our meta-analysis of clinical cohort studies provides evidence that the PON1 Q192R polymorphism may increase the risk of MACE and stent thrombosis in patients receiving antiplatelet treatment after PCI.     

The C161T polymorphism in the peroxisome proliferator-activated receptor gamma gene (PPARγ) is associated with risk of coronary artery disease: a meta-analysis

The researches attempting to associate the PPARγ C161T polymorphism with coronary artery disease (CAD) yielded complicated and contradictory results. We aimed for more precise estimate of the relationship and conducted a comprehensive meta-analysis. Publications written in English or Chinese were screened in MEDLINE, Embase, CNKI, Wanfang and CBM. Data on 11 studies including 3,020 cases and 2,853 controls were extracted. A random-effects model was available to synthesize the inconsistent outcomes of the individual studies, while addressing between-study heterogeneity and publication bias. The PPARγ C161T polymorphism followed Hard-Weinberg Equilibrium for all studies (P > 0.05).Overall, there was no evidence for a significant association under all genetic models but with distinct heterogeneity (T vs. C: P = 0.29, OR = 0.91, 95 %CI 0.77–1.08, P _{heterogeneity} = 0.004, I ² = 61.2 %). However, in the subgroup analysis by ethnicity, the T allele carriers showed a prominent 26 % risk reduction of CAD among Chinese (dominant genetic model: P = 0.03, 95 %CI 0.57–0.97, P _{heterogeneity} = 0.03, I ² = 56.1 %). After dividing into population source, the significance of CAD risk reduction was strengthened in hospital-based studies (allele comparison: P = 0.04, OR = 0.82, 95 %CI 0.67–1.00, P _{heterogeneity} = 0.04, I ² = 52.5 %; dominant model: P = 0.01, OR = 0.73, 95 %CI 0.57–0.92, P _{heterogeneity} = 0.05, I ² = 50.8 %). There was no obvious publication bias verified in the method of funnel plot and Egger’s linear regression test (t = ?0.11, P = 0.913). Taken together, our results revealed the PPARγ C161T polymorphism might play a moderate protective effect on developing CAD among Chinese, but not among Caucasians.     

Association between the NBS1 Glu185Gln polymorphism and lung cancer risk: a systemic review and meta-analysis

Nijmegen Breakage Syndrome protein 1 (NBS1) is one of the most important DNA repair proteins playing important roles in maintaining the genomic stability of NDA. Previous studies regarding the association between NBS1 8360G>C (Glu185Gln) polymorphism and lung cancer reported conflicting results. To derive a more precise estimation of this association, a systemic review and meta-analysis was performed. We performed a meta-analysis using eligible case–control studies to summarize the data on the association between the NBS1 Glu185Gln polymorphism and lung cancer risk. Odds ratios (ORs) with corresponding 95 % confidence intervals (95 %CIs) were pooled to assess the association between NBS1 Glu185Gln polymorphism and lung cancer risk. Six case–control studies with a total of 2,348 lung cancer cases and 2,401 controls without canner were included into the meta-analysis. Overall, there was an association between NBS1 Glu185Gln polymorphism and lung cancer risk under the dominant comparison model (fixed-effects OR _{GluGln/GlnGln vs. GluGlu}  = 1.21, 95 % CI 1.07–1.37, P = 0.002, I ² = 8.1 %). Subgroup analysis by race suggested a significant association between NBS1 Glu185Gln polymorphism and lung cancer risk in Asians (fixed-effects OR _{GluGlnGlnGln vs. GluGlu}  = 1.22, 95 % CI 1.06–1.41, P = 0.005) but not in Caucasians (fixed-effects OR _{GluGlnGlnGln vs. GluGlu}  = 1.17, 95 % CI 0.91–1.50, P = 0.220). This meta-analysis supports that there is an association between NBS1 Glu185Gln polymorphism and lung cancer risk. More studies are needed to further verify this association.     

Association between the MMP-9−1562 C>T polymorphism and the risk of stroke: a meta-analysis

Matrix metalloproteinase (MMP)-9 so far is identified as extremely large and complicated MMP family member. Recently, dozens of studies have explored the association between a promoter polymorphism (?1562 C>T) in MMP-9 and stroke susceptibility. However, the conclusions of these studies still remain equivocal. Therefore, our current meta-analysis was conducted to investigate whether or not the MMP-9 promoter polymorphism is related to the risk of stroke. Electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and the Chinese Biomedical Literature Database) were searched to obtain all the available studies investigating this polymorphism and stroke from inception to October 2013. Overall and subgroup analyses were rigorously conducted after data extraction. Pooled odds ratio (OR) corresponding to 95 % confidence interval (CI) were estimated. The statistical analysis was performed using Review Manager 5.2. Totally, seven studies involving 1,624 cases and 1,525 controls were identified. The overall results suggested that there was no association of the C?1562T variant on stroke risk under the T allele versus C allele [OR _{T vs. C} 0.98, 95 % CI (0.84, 1.15), P = 0.84], the dominant model [OR _{TT+TC vs. CC} 0.95, 95 % CI (0.81, 1.13), P = 0.59], the recessive model [OR _{TT vs. TC+CC} 1.55, 95 % CI (0.86, 2.81), P = 0.15], the homozygote comparison [OR _{TT vs. CC} 1.48, 95 % CI (0.82, 2.68), P = 0.20] and the heterozygote comparison [OR _{TC vs. CC} 0.93, 95 % CI (0.78, 1.10), P = 0.38]. In the subgroup analyses by ethnicity, age, stroke type and source of controls, no significant relations were observed in any genetic models. Our results indicated that MMP-9?1562 C>T polymorphism was not a risk factor for stroke. Further studies should focus on gene–gene and gene–environment interactions, and provide a more convincing explanation for this association.     

An updated meta-analysis of endothelial nitric oxide synthase gene: Three well-characterized polymorphisms with ischemic stroke

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of ischemic stroke (IS), but the results are still debatable. A meta-analysis was performed to investigate the association between the eNOS gene polymorphisms in IS risk. Case–control studies on the association between the G894T, T-786C, and 4b/a polymorphisms and IS were searched up to July 2012, and the genotype frequencies in the control group were found to be consistent with the Hardy–Weinberg equilibrium (HWE). The effect summary odds ratio (OR) and 95% confidence intervals (CIs) were obtained. Meta-regression was used to explore the potential sources of heterogeneity. Funnel plots and Egger's test was used to estimate small study biases, and heterogeneity was assessed by chi-square-based Q-test and I² test. There were total 6537/6475 cases/controls for G894T, 3459/3951 cases/controls for 4b/a, and 2125/2673 cases/controls for T-786C polymorphism. For G894T and 4b/a, a significant association of 894 T allele and 4a allele with increased risk of IS was found in Asians (TT + GT vs. GG: p < 0.00001, OR = 1.60, 95% CI = 1.38–1.79, P_{heterogeneity} = 0.11; aa + ba vs. bb: P < 0.00001, OR = 1.60, 95% CI = 1.30–1.97, P_{heterogeneity} = 0.02), but not in Caucasians (TT + GT vs. GG: P = 0.60, OR = 0.94, 95% CI = 0.75–1.19, P_{heterogeneity} = 0.002; aa + ba vs. bb: P = 0.13, OR = 0.81, 95% CI = 0.62–1.06, P_{heterogeneity} = 0.63). For T-786C polymorphism, there were no significant differences in genotype distribution between IS and control in Asians (CC + TC vs. TT: P = 0.15, OR = 1.14, 95% CI = 0.95–1.37, P_{heterogeneity} = 0.94) and in Caucasians (CC + TC vs. TT: P = 0.72, OR = 0.96, 95% CI = 0.75–1.22, P_{heterogeneity} = 0.53). This analysis provides strong evidence that the eNOS T-786C gene polymorphism is not associated with IS, the G894T and 4b/a polymorphisms might be associated with IS, at least in Asians.     

HIF-1α 1772 C/T and 1790 G/A Polymorphisms Are Significantly Associated with Higher Cancer Risk: An Updated Meta-Analysis from 34 Case-Control Studies

Background

HIF-1 activates various genes in cancer progression and metastasis. HIF-1α 1772 C/T and 1790 G/A polymorphisms are reportedly associated with cancer risk; however, the results are inconclusive.

Methodology/Principal Findings

A meta-analysis of 34 studies that involved 7522 cases and 9847 controls for 1772 C/T and 24 studies that involved 4884 cases and 8154 controls for 1790 G/A was conducted to identify the association of C/T and G/A polymorphisms with cancer risk. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association.HIF-1α 1772 C/T and 1790 G/A polymorphisms were associated with higher cancer risk in homozygote comparison (1772C/T: TT vs. CC: OR = 2.45, 95% CI: 1.52, 3.96; P _{heterogeneity} = 0.028; 1790G/A: AA vs. GG: OR=4.74, 95% CI: 1.78, 12.6; P _{heterogeneity} < 0.01), dominant model (1772C/T: TT/CT vs. CC: OR = 1.27, 95% CI: 1.04, 1.55; P _{heterogeneity} < 0.01, 1790G/A: AA/GA vs. GG: OR = 1.65, 95% CI: 1.05, 2.60; P _{heterogeneity} < 0.01), T allele versus C allele (T vs. C: OR = 1.42, 95% CI: 1.18, 1.70; P _{heterogeneity} < 0.01), and A allele versus G allele (A vs. G: OR = 1.83, 95% CI: 1.13, 2.96; P _{heterogeneity} < 0.01). On a subgroup analysis, the 1772 C/T polymorphism was significantly linked to higher risks for breast cancer, lung cancer, prostate cancer, and cervical cancer, whereas the 1790 G/A polymorphism was significantly linked to higher risks for lung cancer and prostate cancer. A significantly increased cancer risk was found in both Asians and Caucasians for 1772C/T polymorphism, whereas a significantly increased cancer risk was found in Caucasians in the heterozygote comparison and recessive model for 1790G/A polymorphism.

Conclusions

HIF-1α 1772 C/T and 1790 G/A polymorphisms are significantly associated with higher cancer risk.     

Molecular Epidemiologic Correlation Analysis Between Caspase3 Gene Polymorphism and Gastric Cancer Susceptibility

The objective was to analyze the relation between gastric cancer susceptibility and gene polymorphism, providing a reference for epidemiologic research of gastric cancer etiology. Two hundred and eighty gastric cancer cases were selected, and 280 healthy cases with the same gender, age (±5), and residence place were selected as control group, with proportion of 1:1. Tag single nucleotide polymorphism was used for screening polymorphism of caspase3, which was combined with logistic regression model and multi-point joint analysis to analyze relation between different genotypes and gastric susceptibility. In analysis of gene polymorphism of caspase3 intrinsic apoptotic pathway and gastric cancer susceptibility, polymorphism of CASP3 rs4647693, CASP3 rs12108497 and CASP3 rs4647610 increased gastric cancer risk (rs4647693: OR_GA 1.61, 95 % CI 1.06–2.28; rs12108497: OR_TC 1.55, 95 % CI 1.09–2.18; OR_CC 2.45, 95 % CI 1.08–4.16; rs4647610: OR_AG 1.71, 95 % CI 1.14–2.31; OR_GG 1.60, 95 % CI 1.23–2.34). Gastric cancer risk of haplotype AGGC carrier was significantly higher than that of haplotype GGAT as control (OR 1.44, 95 % CI 1.07–2.19). Gene polymorphism and haplotype of caspase3 can increase gastric cancer risk. However, it still needs to be verified by a large-sample and multicenter epidemiologic research.     

The association between common genetic variant of microRNA-499 and cancer susceptibility: a meta-analysis

Published data on the association between microRNA-499 (miR-499) rs3746444 T>C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of this relationship, a comprehensive meta-analysis was performed on nine published studies, with a total sample of 4,794 cases and 5,971 controls. Overall, no significant association was found between miR-499 polymorphism and cancer risk after all studies were pooled into the meta-analysis. However, in the subgroup analysis by ethnicity, significant association with an increased risk was found in Asian (CC vs. TT: OR = 1.439, 95 % CI = 1.118–1.852, P = 0.005, p-heterogeneity = 0.116). Moreover, in the the subgroup analysis by cancer type, this SNP was associated with an increased risk of breast cancer in the recessive model (OR = 1.077, 95 % CI = 1.008–1.151, P = 0.028, p-heterogeneity = 0.125). Our findings support the view that miR-499 rs3746444 T>C polymorphism is associated with breast cancer and the C allele can increase cancer susceptibility in Asian.     

Evaluation of the Association Between CD143 Gene Polymorphism and Psoriasis

Increased CD143 activity has been detected in various skin tissues, and this increase is partially caused by the intronic ID polymorphism. The genetic contribution of CD143 ID polymorphism to the progression of psoriasis, the commonest skin disease, has been extensively investigated, but reported with inconsistent results. The aim of this work was to gain new insights to shed light on the association between CD143 ID polymorphism and psoriasis risk. We systematically identified the studies examining the association of CD143 ID polymorphism with psoriasis risk. A meta-analysis combining data from all eligible studies was carried out. To evaluate the genetic association, we calculated odds ratio (OR) and its 95 % confidence intervals (CIs) for both genotypic models and allelic model. The final pooling dataset comprised ten studies. Meta-analysis of total samples did not suggest a notable association with psoriasis risk. However, subgroup analysis by ethnicity revealed a statistically significant association in East Asian samples (DD + ID vs. II: OR 0.86, 95 % CI 0.75–0.99, P_{heterogeneity} = 0.970; DD vs. ID: OR 0.85, 95 % CI 0.73–0.99, P_{heterogeneity} = 0.868; D vs. I: OR 0.86, 95 % CI 0.76–0.97, P_{heterogeneity} = 0.994). This meta-analysis demonstrated that the presence of CD143 ID polymorphism may modify the risk of psoriasis in individuals with East Asian ancestry.     

CTLA-4 polymorphisms and systemic lupus erythematosus (SLE): a meta-analysis

The aim of this study was to summarize results on the association of cytotoxic T-lymphocyte antigen-4 (CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism with systemic lupus erythematosus (SLE) susceptibility by using the meta-analysis. We searched all the publications about the association between CTLA-4) promoter exon-1 +49 and 1722T/C polymorphism and SLE from PubMed, Elsevier Science Direct, Chinese Biomedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang (Chinese). Previous CTLA-4 association studies with SLE, however, have produced inconsistent results. We have performed a meta-analysis to better assess the purported associations. A total of 17 independent studies (to June 2012) testing association between one or more CTLA-4 polymorphisms and SLE were used in this analysis. We have compared allele and genotype frequencies at two polymorphic sites found in exon-1 (at +49) and the promoter region (at ?1722). The data demonstrate that the exon-1 +49 polymorphism is associated with SLE susceptibility in Asian population. The overall risk, measured by odds ratio (OR), stratification by ethnicity indicates the exon-1 +49 GG+GA genotype is associated with SLE, at least in Asians (OR = 0.85, 95 % CI = 0.73–0.99, P = 0.04 for GG+GA vs. AA; OR = 0.85, 95 % CI = 0.72–1.00, P = 0.05 for AG vs. AA). Similar trends are found in allele-specific risk estimates and disease association. Overall, there was significant association between the 1722T/C polymorphism and overall SLE risks (OR = 0.78, 95 % CI = 0.63–0.97, P = 0.04 for GG+GA vs. AA, OR = 0.87, 95 % CI = 0.76–0.99, P = 0.04 for G vs. A) in Asian population.In summary, this meta-analysis demonstrates that the CTLA-4 promoter +49A/G and promoter ?1722C/T polymorphism may confer susceptibility to SLE, especially in Asian-derived population.     

Association between the CYP1A2-164 A/C polymorphism and colorectal cancer susceptibility: a meta-analysis

To date, epidemiological studies have assessed the association between CYP1A2-164 A/C polymorphism and colorectal cancer susceptibility. However, the results of these studies remained controversial. We aimed to examine the associations by conducting a meta-analysis of case–control studies. A total of 11 studies including 5,093 cases and 5,941 controls evaluated the association between the CYP1A2-164 A/C polymorphism and colorectal cancer susceptibility. No significantly associations were found in all genetic models (CC vs. AA: OR = 1.14, 95 % CI = 0.93–1.40; AC vs. AA: OR = 1.05, 95 % CI = 0.91–1.20; dominant model: OR = 1.08, 95 % CI = 0.95–1.24; recessive model: OR = 1.10, 95 % CI = 0.95–1.28). In the subgroup analysis by ethnicity or source of controls, there were still no significant associations detected in all genetic models. This meta-analysis suggested the CYP1A2-164 A/C polymorphism was not a risk factor for increasing colorectal cancer, further large and well-designed studies are needed to confirm these conclusions.