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.     

Effects of common polymorphisms rs2910164 in miR-146a and rs3746444 in miR-499 on cancer susceptibility: a meta-analysis

MicroRNAs (miRNAs) are a class of new non-coding RNA, which may play a more important role in the pathogenesis of human cancers. Rs2910164 in miR-146a and rs3746444 in miR-499 are shown to be associated with increased/decreased cancer risk. We performed a meta-analysis to systematically summarize the possible association. We retrieved the relevant articles from PubMed databases. Studies were selected using specific inclusion and exclusion criteria. ORs and 95% CIs were calculated to access the strength of association between microRNA polymorphism and cancer risk. All analyses were performed using the Stata software. Twenty-nine studies were included in this meta-analysis. There were not significant associations between miR-146a rs2910164 and miR-499 rs3746444 polymorphisms with overall cancer risk. In the subgroup analysis by ethnicity, significantly affected cancer risks were found among Asians for both rs2910164 (GC vs. GG: OR = 0.89, 95% CI = 0.82–0.96; CC vs. GG: OR = 0.80, 95% CI = 0.66–0.97; GC + CC vs. GG: OR = 0.86, 95% CI = 0.76–0.97; C vs. G: OR = 0.91, 95% CI = 0.82–1.00) and rs3746444 (GG + AG vs. AA: OR = 1.21, 95% CI = 1.00–1.46). In the tumor type subgroup analysis, rs2910164 C allele decreased the risk of hepatocellular carcinoma (C vs. G: OR = 0.89, 95% CI = 0.80–1.00) and cervical squamous cell carcinoma (C vs. G: OR = 0.72, 95% CI = 0.62–0.84). The rs2910164 in miR-146a and the rs3746444 in miR-499 are likely to be associated with cancer risk.     

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.     

Association between interleukin-18 polymorphisms and systemic lupus erythematosus: a meta-analysis

The aim of this study was to determine whether the three functional interleukin-18 (IL-18) promoter ?607 C/A (rs1946518), ?137 G/C (rs187238), and ?1297 C/T (rs360719) polymorphisms confer susceptibility to systemic lupus erythematosus (SLE) in ethnically different populations. Meta-analysis was conducted on the associations between these IL-18 polymorphisms and SLE using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 11 comparisons (nine studies) involving 8,453 subjects (2,928 SLE patients and 5,525 controls) were included in the meta-analysis. In all study subjects, meta-analysis showed no association between SLE and the IL-18 ?607 C allele (odds ratio [OR] = 1.065, 95 % confidence interval [CI] = 0.870–1.303, p = 0.541). However, stratification by ethnicity indicated a significant association between this allele and SLE in Europeans (OR = 0.864, 95 % CI = 0.757–0.986, p = 0.031), but not in Asians (OR = 1.230, 95 % CI = 0.902–1.676, p = 0.190). Meta-analyses showed the same pattern for the IL-18 ?607 C allele using the dominant and additive models. Meta-analysis of the IL-18 ?137 G/C polymorphism showed no association between SLE and the IL-18 ?137 G allele in all study subjects (OR = 0.916, 95 % CI = 0.836–1.003, p = 0.057), but stratification by ethnicity indicated a significant association between this allele and SLE in Asians (OR = 0.792, 95 % CI = 0.629–0.997, p = 0.047), but not in Europeans (OR = 0.930, 95 % CI = 0.839–1.032, p = 0.171). Furthermore, meta-analysis showed that the IL-18 ?1297 C allele was significantly associated with SLE in all study subjects and in Europeans (OR = 1.240, 95 % CI = 1.052–1.482, p = 0.010 and OR = 1.303, 95 % CI = 1.050–1.617, p = 0.016). This meta-analysis shows that the IL-18 ?607 C/A and ?1297 C/T polymorphism are associated with the development of SLE in Europeans, and the IL-18 ?137 G/C polymorphism is associated with SLE in Asians.     

Association between tumor necrosis factor-α promoter −308 A/G, −238 A/G, interleukin-6 −174 G/C and −572 G/C polymorphisms and periodontal disease: a meta-analysis

The aim of this study was to determine whether tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) promoter polymorphisms confer susceptibility to periodontitis in ethnically different populations. A literature search was performed using PubMed and Embase and a meta-analysis of the identified studies was conducted to explore the associations between TNF-α ?308 A/G, ?238 A/G, IL-6 promoter ?174 G/C and ?572 G/C polymorphisms and periodontitis. Seventeen comparison studies for the TNF-α ?308 A/G polymorphism and three studies for the TNF-α ?238 A/G polymorphism were included in the meta-analysis. And 16 separate studies for the IL-6 ?174 G/C polymorphism and 10 studies for the IL-6 ?572 G/C polymorphism were considered in our meta-analysis. Analysis after stratification by ethnicity indicated that the TNF-α ?308 A allele was associated with periodontitis in Brazilian, Asian, and Turkish populations (OR = 0.637, 95 % CI = 0.447–0.907, p = 0.013; OR = 0.403, 95 % CI = 0.204–0.707, p = 0.009; OR = 1.818, 95;  % CI = 1.036–3.189, p = 0.037). The meta-analysis showed no association between the TNF-α ?238 A/G polymorphism and periodontitis. The meta-analysis indicated an association of the IL-6 ?174 G/C polymorphisms with periodontitis in Brazilian populations (OR for GG + GC = 2.394, 95 % CI = 1.081–5.302, p = 0.031). Stratification by ethnicity and disease type indicated an association between the IL-6 ?572 G allele and chronic periodontitis (OR = 1.585, 95 % CI = 1.030–2.439, p = 0.036), and periodontitis in Europeans (OR = 2.118, 95 % CI = 1.254–3.577, p = 0.005). This meta-analysis demonstrates that the TNF-α ?308 A/G polymorphism confers susceptibility to periodontitis in Brazilian, Asian and Turkish populations. The IL-6 ?174 G/C polymorphism may confer susceptibility to periodontitis in Brazilians, and the IL-6 ?572 G/C polymorphism may be associated with susceptibility to periodontitis in Europeans, and chronic periodontitis.     

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 cyclooxygenase-2 gene polymorphisms and risk of periodontitis: a meta-analysis involving 5653 individuals

There ?765G > C, ?1195G > A, and 8473T > C polymorphisms in cyclooxygenase-2 (COX-2) gene polymorphisms and periodontitis risk were investigated based on published studies; however, their results could not give a conclusive result. Hence, we performed this meta-analysis of six published studies with eight case–control studies including these three polymorphisms which searched from PubMed and Web of Science up to October 15th, 2013. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were calculated to evaluate the association between the three polymorphisms of COX-2 and periodontitis risk. The results from 2,580 periodontitis patients and 3,073 healthy controls showed that none of ?765G > C, ?1195G > A, or 8473T > C polymorphism was not associated with periodontitis susceptibility [Take ?765G > C for example: OR = 0.94, 95 % CI = (0.57–1.53) for C vs. G; OR = 2.34, 95 % CI = (0.72–7.62) for CC vs. GG; OR = 0.68, 95 % CI = (0.46–1.01) for CG vs. GG; OR = 0.81, 95 % CI = (0.52–1.27) for (CG+GG) vs. GG; OR = 2.57, 95 % CI = (0.80–8.29) for CC vs. (GG+CG)]. In subgroup analyses according to the type of periodontitis and ethnicity for ?765G > C and ?1195G > A, and deviations in Hardy–Weinberg equilibrium for ?765G > C, we only observe a boundary association between ?1195G > A polymorphism and Asian population. However, due to limitations of this meta-analysis, the results should treat with caution and we suggest the further researches should be carried out to verify our results.     

Toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms and periodontitis susceptibility: a meta-analysis

The aim of this study was to determine whether the toll-like receptor (TLR) and matrix metalloproteinase (MMP) polymorphisms confers susceptibility to periodontitis in ethnically different populations. A literature search using PubMed and Embase provided the data to conduct a meta-analysis on the associations between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-1 ?1607 G1/G2 and MMP-9 ?1562 C/T polymorphisms and periodontitis. A total of 32 studies (14 on TLR polymorphisms and 18 on MMP polymorphisms) were considered in the meta-analysis. The meta-analysis showed no association between periodontitis and the TLR2 753Arg allele (Odds ratio [OR] = 0.962, 95 % confidence interval [CI] = 0.662–1.400, p = 0.841). Meta-analysis of the TLR4 Asp299Gly and Thr399Ile polymorphisms showed no association between periodontitis and the TLR4 299Asp allele in all study subjects (OR = 0.984, 95 % CI = 0.761–1.271, p = 0.900; OR = 1.030, 95 % CI = 0.748–1.418, p = 0.854). Meta-analysis showed an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians (OR = 3.778, 95 % CI = 1.210–11.80, p = 0.022). Meta-analysis containing only studies in Hardy–Weinberg equilibrium revealed no association between chronic periodontitis and the MMP-9 ?1562TT genotype (OR = 0.638, 95 % CI = 0.265–1.533, p = 0.315). This meta-analysis demonstrates a lack of association between the TLR2 Arg753Gln, TLR4 Asp299Gly, Thr399Ile, MMP-9 ?1562 C/T polymorphisms and periodontitis, but shows an association between the MMP-1 ?1607 G2G2 genotype and periodontitis in Asians.     

Associations between FCGR2A rs1801274, FCGR3A rs396991, FCGR3B NA1/NA2 polymorphisms and periodontitis: a meta-analysis

The aim of this study was to determine whether the Fcγ receptors (FCGRs) polymorphisms confer susceptibility to periodontitis in ethnically different populations. We did a literature search using PubMed and Embase, and conducted a meta-analysis on the associations between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and periodontitis using allele contrast, the recessive model, the dominant model, and the homozygote contrast. A total of 17 separate comparisons with 1,421 patients with periodontitis and 1,454 controls, involving six Caucasian, six East Asian, two African and one South Asian population were considered in the meta-analysis. Meta-analysis of the FCGR2A H131R polymorphism showed no association between periodontitis and the FCGR2A R allele (OR = 0.987, 95 % CI = 0.881–1.107, p = 0.827). Stratification by ethnicity revealed an association between the RR+RH genotype with periodontitis in Caucasian population (OR = 0.624, 95 % CI = 0.479–0.813, p = 4.7 × 10^?5), but not in East Asian, and African populations. Meta-analysis of the FCGR3A F158V polymorphism revealed an association between the FCGR3A V allele and periodontitis is in Caucasians (OR = 1.457, 95 % CI = 1.014–2.092, p = 0.042), but not in East Asians and Africans. In addition, analysis using the dominant model and homozygote contrast showed the same pattern for the FCGR3A V allele. Meta-analysis of the FCGR3B NA1/NA2 polymorphism using the recessive model revealed a significant association between the NA2/NA2 genotype and periodontitis in aggressive periodontitis (OR = 2.853, 95 % CI = 1.673–4.863, 1.1 × 10^?5). This meta-analysis demonstrates that the FCGR2A, and FCGR3A polymorphisms may confer susceptibility to periodontitis in Caucasians, and that the FCGR3B polymorphism may be associated with susceptibility to aggressive periodontitis.     

NBS1 rs1805794G>C polymorphism is associated with decreased risk of acute myeloid leukemia in a Chinese population

As a key encoding protein gene of MRN (MRE11-RAD50-NBS1) complex, NBS1 plays a crucial role in maintaining genomic stability and preventing cell apoptosis, inflammation and tumorgenesis. Single nucleotide polymorphisms (rs2735383 and rs1805794) in NBS1 have been frequently studied in some cancers with discordant results in previous case–control studies. However, the relationship between these two functional polymorphisms and the susceptibility to acute myeloid leukemia (AML) in Chinese population has not been investigated. We performed a case–control study with 428 patients and 600 controls to detect the association between the two polymorphisms of NBS1 and the risk of AML in a Chinese population. The polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) method was carried out to determine the genotypes of potential functional SNPs in NBS1 gene. The results showed that compared with the homozygous carriers rs1805794CC, rs1805794GC genotype was significantly associated with decreased risk of AML in total subjects (adjusted odds ratio (OR) = 0.50; 95 % CI = 0.37–0.67), the risk decreased even further in those carrying rs1805794GG genotype (OR = 0.23; 95 % CI = 0.16–0.34). No significant association was found between rs2735383C>G polymorphism and the risk of AML (OR = 0.93; 95 % CI = 0.71–1.22 for GC; OR = 0.78; 95 % CI = 0.53–1.13 for CC, P = 0.152). These findings indicated that rs1805794G/C polymorphism in NBS1 may play a protective role in mediating the risk of AML.     

CCND1 G870A polymorphism interaction with cigarette smoking increases lung cancer risk: meta-analyses based on 5008 cases and 5214 controls

Evidence indicates CCND1 G870A polymorphisms as a risk factor for a number of cancers. Increasing studies have been conducted on the association of CCND1 G870A polymorphism with lung cancer risk. However, the results were controversial. The aim of the present study was to derive a more precise estimation of the relationship. Meta-analyses examining the association between CCND1 G870A polymorphism and lung cancer were performed. Subgroup analyses regarding ethnicity, smoking status, histological types and source of controls were also implemented. All eligible studies for the period up to May 2012 were identified. The overall data from ten case–control studies including 5,008 cases and 5,214 controls indicated that variant A allele may have an association with increased lung cancer risk (AA vs GG: OR = 1.21; 95 % CI = 1.08–1.36, dominant model: OR = 1.09; 95 % CI = 1.00–1.19, recessive model: OR = 1.23; 95 % CI = 1.01–1.49). In the subgroup analysis by ethnicity, A allele may elevate lung cancer risk among Asians but not Caucasians or Mixed ethnicities. In smoking status subgroup, A allele was shown to associate with increased lung cancer risk among smokers but not non-smokers. In the subgroup analysis by histological types, increased cancer risks were shown in adenocarcinoma but not squamous cell carcinoma, under the homozygote comparison and recessive models. Collectively, the results of the present study suggest that CCND1 G870A polymorphism might be a low-penetrant risk factor for lung cancer, particularly among Asians and smokers. Moreover, homozygous AA alleles might have a correlation with increased lung adenocarcinoma susceptibility.     

The novel human MRC1 gene polymorphisms are associated with susceptibility to pulmonary tuberculosis in Chinese Uygur and Kazak populations

The MRC1 gene, encoding the human mannose receptor (MR), is a member of the C-type lectin receptors family. MR can recognize and bind to Mycobacterium tuberculosis by the extracellular structure, and play a role in antigen-presenting and maintaining a stable internal environment. This study aimed to investigate potential associations of SNPs in exon 7 of the MRC1 gene with pulmonary tuberculosis (TB). G1186A, G1195A, T1212C, C1221G, C1303T and C1323T were genotyped using PCR and DNA sequencing in 595 Chinese Uygur and 513 Kazak subjects. In the Uygur, the frequency of allele G (P = 0.031, OR = 1.29, 95 % CI = 1.02–1.62) and AA genotype (P = 0.033, OR = 1.64, 95 % CI = 1.04–2.60) for G1186A was lower in the pulmonary TB than healthy control and were significantly correlated with pulmonary TB. After adjustment for age and gender, G1186A was found to be additive models in association with pulmonary TB (P = 0.04, OR = 1.27, 95 % CI = 1.01–1.60). By calculating linkage disequilibrium, the frequency of haplotype GGTCCT (P = 0.032, OR = 0.75, 95 % CI = 0.57–0.97) and GGTCCC (P = 0.044, OR = 0.57, 95 % CI = 0.33–0.99) was significantly associated with pulmonary TB. No association was found between other SNPs and pulmonary TB. In the Kazak, all SNPs were not associated with pulmonary TB. Our results suggest that genetic factors play an important role in susceptibility to pulmonary TB at the individual level, and provide an experimental basis to clarify the pathogenesis of pulmonary TB.     

Associations between TNF-α −308 A/G and lymphotoxin-α +252 A/G polymorphisms and susceptibility to sarcoidosis: a meta-analysis

Several studies have examined the effects of the tumor necrosis factor-α (TNF-α) ?308 A/G and lymphotoxin-α (LT-α) +252 A/G polymorphisms on susceptibility to sarcoidosis, showing mixed results. The purpose of this study was to examine whether the TNF-α ?308 A/G and LT-α +252 A/G polymorphisms confer susceptibility to sarcoidosis. We did a literature search from MEDLINE and EMBASE indices, and conducted a meta-analysis examining the association between TNF-α ?308 A/G and LT-α +252 A/G polymorphisms and sarcoidosis. A total of 13 separate comparisons including 1,396 patients with sarcoidosis and 2,344 controls were considered in our meta-analysis. The meta-analysis revealed a significant association between the TNF-α ?308 A allele and sarcoidosis (odds ratio [OR] = 1.480, 95 % confidence interval [CI] 1.057–2.073, p = 0.002). Stratification by ethnicity indicated an association between the TNF-α ?308 A allele polymorphism and sarcoidosis in Europeans (OR = 1.445, 95 % CI = 1.010–2.065, p = 0.044), but not Asians (OR = 4.693, 95 % CI = 0.548–40.29, p = 0.158). The results also showed a significant association between the LT-α +252 G allele and sarcoidosis (OR = 1.266, 95 % CI = 1.048–1.528, p = 0.014). Stratification by ethnicity indicated an association between the LT-α +252 G allele and sarcoidosis in Europeans (OR = 1.307, 95 % CI = 1.045–1.635, p = 0.019), but not in Asians (OR = 1.169, 95 % CI = 0.824–1.660, p = 0.381). Our meta-analysis demonstrates that the TNF-α ?308 A/G and LT-α +252 A/G polymorphisms are associated with susceptibility to sarcoidosis in an European population.     

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 vacA genotypes and the risk of duodenal ulcer: a meta-analysis

Epidemiological studies have reported the relationship between vacuolating cytotoxin A (vacA) s-/m- region genotypes and duodenal ulcer (DU), but the results remained inconclusive. We performed the present meta-analysis to investigate a more authentic association between vacA s-/m- region genotypes and DU. Literature search was performed by searching Embase, PubMed and ISI Web of Science databases as well as checking references from identified articles, reviews and the abstracts presented at related scientific societies meetings. The association was assessed by combined odds ratio (OR) with 95 % confidence interval (CI). A total of 42 studies were included in our final meta-analysis. The combined ORs (95 % CIs) showed that vacA s1 (OR = 2.96, 95 % CI = 2.34–3.75), m1 (OR = 1.46, 95 % CI = 1.05–2.04) and s1m1 (OR = 1.89, 95 % CI = 1.47–2.42) were associated with increased DU risk significantly in the overall studied population. Subgroup analyses by ethnicity showed that vacA s1 increased the risk of DU in Asian countries (OR = 1.92, 95 % CI = 1.30–2.83), European countries (OR = 3.58, 95 % CI = 2.13–6.03) and Latin American countries (OR = 4.20, 95 % CI = 2.21–7.98); vacA m1 increased the risk of DU in Latin American countries (OR = 2.98, 95 % CI = 1.59–5.56); vacA s1m1 increased the risk of DU in Asian countries (OR = 2.04, 95 % CI = 1.12–3.73) and Latin American countries (OR = 2.05, 95 % CI = 1.20–3.48); vacA s2m1 increased the risk of DU in Latin American countries (OR = 2.30, 95 % CI = 1.17–4.50). The data suggest that genotype testing of vacA s- and m- region will be useful in screening susceptible individuals for DU development.     

The CTLA-4 +49 A/G, CT60 A/G and PTPN22 1858 C/T polymorphisms and susceptibility to vitiligo: a meta-analysis

The aim of this study was to explore whether cytotoxic T lymphocyte antigen-4 (CTLA-4) +49 A/G, CT60 A/G, and protein tyrosine phosphatase nonreceptor 22 (PTPN22) 1858 C/T polymorphisms confer susceptibility to vitiligo. A meta-analysis was conducted of the associations between the CTLA-4 +49 A/G, CT60 and PTPN22 1858 C/T polymorphisms and vitiligo using; (1) allele contrast, (2) the recessive model, (3) the dominant model, and (4) the additive model. A total of 14 separate comparisons were considered in our meta-analysis consisting of 3,404 patients with vitiligo and 5,069 controls (nine studies with 1,252 cases and 2,152 controls for the CTLA-4 polymorphisms and five studies with 1,800 cases and 3,269 controls for the PTPN22 polymorphism). Meta-analysis showed no association between vitiligo and the CTLA-4 +49 A/G polymorphism in all study subjects (OR of the G allele = 1.186, 95 % CI = 0.893–1.575, p = 0.240) and in European (OR = 1.016, 95 % CI = 0.873–1.182, p = 0.838). However, meta-analysis of the CTLA-4 CT60 A/G polymorphism showed an association between vitiligo and the CTLA-4 CT60 G allele in all study subjects (OR = 1.267, 95 % CI = 1.110–1.447, p = 4.5 × 10^?5) and in the European group (OR = 1.345, 95 % CI = 1.163–1.556, p = 6.3 × 10^?6). Analysis using the recessive model and homozygote contrast showed the same pattern for the CTLA-4 CT60 G allele. Meta-analysis of the PTPN22 1858 C/T polymorphism showed an association between the PTPN22 T allele and vitiligo in all subjects (OR = 1.507, 95 % CI = 1.320–1.720, p < 1.0 × 10^?8) and in European group (OR = 1.530, 95 % CI = 1.339–1.748, p < 1.0 × 10^?8), but not in Asians (OR = 0.482, 95 % CI = 0.152–1.530, p = 0.216). Analysis using the recessive, dominant model, and homozygote contrast showed the same pattern for the PTPN22 T allele. This meta-analysis demonstrates that the CTLA-4 CT60 A/G polymorphism confers susceptibility to vitiligo in Europeans, but no association was found between the CTLA-4 +49 A/G polymorphism and vitiligo susceptibility. The PTPN22 C1858T polymorphism is associated with vitiligo susceptibility in European population.     

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.     

Quantitative assessment of the associations between MTHFR C677T and A1298C polymorphisms and risk of fractures: a meta-analysis

Many studies have investigated the associations between methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms and risk of fractures, but the impact of MTHFR polymorphisms on fractures risk is unclear owing to the obvious inconsistence among those studies. This study aims to quantify the strength of association between MTHFR C677T and A1298C polymorphisms and risk of fractures. We searched the PubMed, Embase and Wanfang databases for articles relating the association between MTHFR C677T and A1298C polymorphisms and risk of fractures in humans. We estimated summary odds ratios (ORs) with their confidence intervals (CIs) to assess the associations. Meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of any site fractures (for T vs. C, OR = 1.17, 95 % CI 1.03–1.32; for TT vs. CC, OR = 1. 31, 95 % CI 1.11–1.54; for TT vs. CT, OR = 1.22, 95 % CI 1.04–1.43; for TT vs. CT/CC, OR = 1.31, 95 % CI 1.13–1.51). Besides, MTHFR A1298C polymorphism was also associated with increased risk of any site fractures. Subgroup meta-analyses suggested MTHFR C677T polymorphism was associated with increased risk of vertebral fractures under three genetic contrast modes (for TT vs. CC, OR = 1.43, 95 % CI 1.05–1.95; for TT vs. CT, OR = 1.36, 95 % CI 1.01–1.85; for TT vs. CT/CC, OR = 1.50, 95 % CI 1.17–1.91), but there was no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures (all P values were more than 0.05). Thus, individuals with homozygote genotype TT of MTHFR C677T have obviously increased risk of vertebral fractures compared those with heterozygote genotype CT or homozygote genotype CC. There is no association between MTHFR C677T polymorphism and risk of hip fractures and non-vertebral fractures.     

Folate intake and MTHFR polymorphism C677T is not associated with ovarian cancer risk: evidence from the meta-analysis

Folate is essential for DNA synthesis and methylation and implicated in the process of carcinogenesis. Several studies inconclusively suggested increased folate intake may reduce ovarian cancer risk. Studies concerning the association between C677T polymorphism in methylenetetrahydrofolate reductase (MTHFR), an important enzyme in folate metabolism, and ovarian cancer risk also resulted in no agreement. The meta-analysis was conducted based on current studies to assess the association between folate intake, the MTHFR C667T polymorphism and ovarian cancer risk. 1,158 cases out of 217,309 participants from four cohort studies, 4,519 cases and 6,031 controls from four case–control studies about folate intake along with 5,617 cases and 9,808 controls from 10 publications concerning the polymorphism were pooled, respectively. We detected no significant association between total folate (RR = 1.04, 95 % confidence interval (CI) = 0.87–1.23) or dietary folate (RR = 0.88, 95 % CI = 0.75–1.05) intake and ovarian cancer risk, and also no significant relationship was found between MTHFR C677T polymorphism and ovarian cancer risk (TT vs. CC: odds ratio (OR) = 1.15, 95 % CI = 0.90–1.46; CT vs. CC: OR = 1.04, 95 % CI = 0.94–1.16). Our analysis indicated neither folate intake nor MTHFR C677T polymorphism is related to altered susceptibility of ovarian cancer.