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.     

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.     

The methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and tumor risk: evidence from 134 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme involved in folate metabolism, which is essential for DNA synthesis and methylation. Genetic variations in the MTHFR gene seem to contribute to a decreased activity of MTHFR, ultimately confer increased susceptibility to cancer. As the most extensively studied polymorphism, MTHFR C677T polymorphism was shown to contribute to cancer susceptibility but the results were inconsistent. The authors performed a meta-analysis including 134 studies (46,207 cases and 69,160 controls) to address the issue. Odds ratios (ORs) with corresponding 95 % confidence intervals (CIs) were used to assess the association. Overall, a significant elevated risk of cancer was associated with the MTHFR C677T polymorphism in T-allele versus C-allele comparison (OR = 1.06, 95 % CI 1.02–1.11, P _{heterogeneity}  < 0.001), homozygote model (OR = 1.08, 95 % CI 1.01–1.17, P _{heterogeneity}  < 0.001) and dominant model (OR = 1.05, 95 % CI 1.00–1.10, P _{heterogeneity}  < 0.001). In the stratified analyses, significantly increased cancer risks were indicated among Asians in all genetic models except for heterozygote model. Further analysis revealed that C677T was significantly associated with an increased risk of esophageal and stomach cancer. This meta-analysis supports an association between the MTHFR C677T polymorphism and increased risk of esophageal and stomach cancer, especially among Asians. Additionally, more high-quality studies and that the covariates responsible for heterogeneity should be controlled to obtain a more conclusive response about the function of MTHFR C677T in cancer.     

Association between the COMT Val158Met polymorphism and breast cancer risk: a meta-analysis of 30,199 cases and 38,922 controls

Many studies have reported the role of COMT Val158Met with breast cancer risk, but the results remained controversial. In addition, previous meta-analysis on COMT Val158Met showed conflicting results. Hence, we performed a meta-analysis to investigate the association between breast cancer and COMT Val158Met (30,199 cases and 38,922 controls) in different inheritance models. When all the eligible studies were pooled into this meta-analysis, there was no evidence of significant association between breast cancer risk and COMT Val158Met polymorphism in any genetic model (dominant model: odds ratio [OR] = 0.99, 95% confidence interval [CI] = 0.94–1.04, P value of heterogeneity test [P _h] = 0.009, I ² = 36.9%; recessive model: OR = 0.97, 95% CI = 0.92–1.02, P _h = 0.044, I ² = 28.6%; additive model: OR = 0.98, 95% CI = 0.91–1.05, P _h = 0.004, I ² = 40.4%). However, significant between-study heterogeneity was detected in any genetic model. Hence, we performed the stratified analysis according to ethnicity, source of controls, menopausal status, and family history. In the stratified analysis by ethnicity significantly decreased breast cancer risk was observed in Caucasian population (recessive model: OR = 0.96, 95% CI = 0.92–1.00, P _h = 0.419, I ² = 3.1%). In conclusion, this meta-analysis indicates that COMT Val158Met polymorphism may be associated with decreased breast cancer risk in Caucasian population. However, a study with the larger sample size is needed to further evaluated gene-environment interaction on COMT Val158Met polymorphisms and breast 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.     

Quantitative Assessment of the Association Between HDMX Polymorphism and Sarcoma

To investigate the effects of the HDMX polymorphism on sarcoma risk. Relevant studies were identified by searching the PubMed, Embase, and Web of Science databases. Data were extracted by two independent investigators. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated using a fixed-effects model to assess the association between the HDMX polymorphism and sarcoma risk. We also conducted heterogeneity test, sensitivity analysis, and publication bias test. A meta-analysis of four published case–control studies involving 1,115 subjects (379 cases and 736 controls) showed no statistical association between the HDMX polymorphism and sarcoma risk (OR_{TT vs. GG}  0.88, 95 % CI  0.68–1.14, P _{heterogeneity}  0.819; OR_{TT + TG vs. GG} 0.95, 95 % CI  0.79–1.15, P _{heterogeneity}  0.937; OR_{TT vs. TG + GG}  0.82, 95 % CI  0.65–1.04, P _{heterogeneity}  0.589; OR_{T allele vs. G allele}  0.91, 95 % CI  0.79–1.05, P _{heterogeneity}  0.727; OR_{TG vs. GG}  0.95, 95 % CI  0.74–1.22, P _{heterogeneity} = 0.869). This null result did not alter when data were stratified according to ethnicity. Our meta-analysis indicates that the HDMX polymorphism is unlikely to contribute to individual susceptibility to sarcoma.     

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.     

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.     

Associations between interferon regulatory factor 5 polymorphisms and rheumatoid arthritis: a meta-analysis

The aim of this study was to determine whether interferon regulatory factor 5 (IRF5) polymorphisms confers susceptibility to rheumatoid arthritis (RA) in populations with different ethnicities. We searched the literature using the Pubmed and Embase databases and conducted meta-analyses on associations between the four IRF5 polymorphisms (rs2004640, rs729302, rs752637, and rs2280714) and RA susceptibility, using fixed and random effects models. A total of 12 comparison studies were considered in this meta-analysis, which in total involved 7,916 RA patients and 6,452 controls, and eight European, three Asian, and one Argentinean population. Meta-analysis showed an association between the minor allele of rs2004640 and RA in all subjects (odds ratio [OR] = 0.928, 95 % confidence interval [CI] = 0.865–0.996, P = 0.037). After stratification by ethnicity, analysis indicated that the minor allele was significantly associated with RA in Europeans (OR = 0.889, 95 % CI = 0.839–0.941, P = 5.03 × 10^?6), but not in Asians (OR = 1.057, 95 % CI = 0.978–1.144, P = 0.164). A direct comparison between anti-citrullinated peptide antibody-positive and -negative patients revealed no difference of the frequency of the rs2004640 minor allele (OR = 1.047, 95 % CI = 0.813–1.348, P = 0.724). Meta-analysis identified a significant association between RA and the minor allele of the rs729302 polymorphism in the overall population (OR = 0.896, 95 % CI = 0.826–0.972, P = 0.009) and in Asians (OR = 0.862, 95 % CI = 0.795–0.935, P = 3.50 × 10^?5), but not in Europeans (OR = 0.951, 95 % CI = 0.877–1.031, P = 0.225). Meta-analysis showed an association between the minor allele of rs752637 and RA in Europeans (OR = 0.858, 95 % CI = 0.789–0.932, P = 3.03 × 10^?5), but not in Asians (OR = 1.035, 95 % CI = 0.918–1.168, P = 0.572). No association was found between the rs2280714 polymorphism and RA susceptibility. This meta-analysis confirms that the IRF5 rs2004640, rs729302 and rs752637 polymorphisms are associated with RA susceptibility in different ethnic groups, especially in Europeans and Asians, but further study of this association is required in other ethnic groups.     

Association of the DNMT3B polymorphism with colorectal adenomatous polyps and adenocarcinoma

DNMT3B is an important enzyme to modulate the methylation status in mammalian cells. The aim of this study is to investigate the correlation of the DNMT3B G39179T polymorphism with the susceptibilities of colorectal adenomatous polyps and adenocarcinoma. This case-control study included 146 colorectal adenomatous polyps, 170 colorectal adenocarcinoma patients, and 157 normal controls. DNMT3B polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism analysis. Family history of colorectal cancer significantly increases the risk of developing colorectal adenomatous polyps and adenocarcinoma. The genotype frequency of DNMT3B polymorphism (T/T and G/T + G/G) in adenocarcinoma patients was significantly different from that in controls (P value = 0.01). Compared with DNMT3B T/T genotype, the G allelotype (G/T + G/G genotype) had lower risk to develop colorectal adenocarcinoma (OR = 0.50, 95% CI = 0.29–0.87); while there was no significant difference between the colorectal adenomatous polyps patients and controls (OR = 0.63, 95% CI = 0.37–1.09), although descending tendency could be found in this polyps group. In the stratification analysis, a significant association was confined to subgroups of age < 55 (OR = 0.31, 95% CI = 0.12–0.84) and males (OR = 0.35, 95% CI = 0.17–0.71). Meanwhile, combined G/T + G/G genotypes were found to have a lower risk in non-drinkers to develop both colorectal adenomatous polyps and adenocarcinoma (OR = 0.54, 95% CI = 0.31–0.96 and OR = 0.48, 95% CI = 0.27–0.84, respectively). This study also showed a distinct difference in the distribution of DNMT3B G39179T SNP in different ethnics. DNMT3B G39179T SNP may be a potential genetic susceptibility factor for adenocarcinoma of the colon, especially in younger Chinese Han non-drinker men.     

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.     

No association between catechol-o-methyltransferase Val108/158Met polymorphism and schizophrenia or its clinical symptomatology in a Mexican population

The gene coding for catecol-o-methyltransferase (COMT), participant in the metabolism of catecholamines, has long been implicated as a candidate gene for schizophrenia. We determined the relation of the COMT Val108/158Met polymorphism with schizophrenia or its symptomatology (negative, disorganized and psychotic dimension). We conducted a case–control study comprising 186 patients with schizophrenia and 247 controls. The diagnosis of schizophrenia was established using the DSM-IV criteria for this illness. The clinical symptomatology was assessed through the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms. No significant differences were found in the distribution of alleles (χ2 = 0.01, df = 1, p = 0.90) or genotypes (χ2 = 1.66, df = 2, p = 0.43) between schizophrenic patients and the control group. Multivariate analysis showed that the COMT Val108/158Met polymorphism has no influence in the clinical symptomatology of schizophrenia. Our results showed no association between COMT Val108/158Met and schizophrenia or evidence for an association between COMT and the clinical symptomatology of this illness. This suggests that the COMT gene may not contribute to the risk for schizophrenia among the Mexican population.     

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.     

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.     

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 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.     

Catechol-<Emphasis Type="Italic">O</Emphasis>-methyltransferase (COMT) Val158Met polymorphism and risk of osteoporotic fracture

Catechol-O-methyltransferase (COMT) is an estrogen degrading enzyme. The COMT Val158Met polymorphism is associated with bone mineral density. The aim of this study was to investigate associations between COMT Val158Met and osteoporotic fractures in Chinese Han patients. Case-control study of 320 patients with osteoporotic fractures and 320 healthy controls were conducted. The COMT Val158Met polymorphism was analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. Patients with osteoporotic fracture had a significantly lower frequency of Val/Val genotype [odds ratio (OR) = 0.62, 95% confidence interval (CI) 0.39–0.99, P = 0.04] than controls. When stratified by the fracture type, there was a significantly lower frequency of Val/Val genotype in patients with vertebral fracture (OR = 0.58, 95% CI 0.36–0.94, P = 0.03) than controls. There was no significant difference in the distribution of each genotype between patients with hip fracture and the control group. Our findings suggest that COMT Val/Val genotype was associated with a lower risk of osteoporotic fracture in Chinese population, especially to vertebral fracture.     

The Cdx-2 polymorphism in the VDR gene is associated with increased risk of cancer: a meta-analysis

The Cdx-2 polymorphism in VDR gene has been extensively investigated for association with cancer risk, however, results of different studies have been inconsistent. The objective of this study is to assess the relationship of the Cdx-2 polymorphism in VDR and cancer risk by meta-analysis. All eligible case–control studies were searched in Pubmed, Embase, CNKI and Wanfang databases. Odds ratios (OR) with the 95 % confidence intervals (CI) were used to assess the association. A total of 12,906 cases and 13,700 controls in 18 case–control studies were included. The results indicated that the AA homozygote carriers had a 16 % increased risk of cancer, when compared with the homozygote GG and heterozygote AG (OR = 1.16, 95 % CI 1.05–1.29 for AA vs. GG+AG). In the subgroup analysis by ethnicity, significant elevated risks were associated with AA homozygote carriers in Caucasians (OR = 1.16, 95 % CI 1.01–1.33, and P = 0.04) and African Americans (OR = 1.31, 95 % CI 1.07–1.61, and P = 0.01). In the subgroup analysis by cancer types, the polymorphism was associated with increased risk of breast cancer (OR = 1.23, 95 % CI 1.04–1.46, and P = 0.02). This meta-analysis suggested that the Cdx-2 polymorphism of VDR gene would be a risk factor for cancer. To further evaluate gene-to-gene and gene-to-environmental interactions between polymorphisms of VDR gene and cancer risk, more studies with large groups of patients are required.