MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

Association of VEGF Gene Polymorphisms with Diabetic Retinopathy: A Meta-Analysis

Background

Studies on the association of vascular endothelial growth factor (VEGF) gene -460T/C and -2578C/A polymorphisms with diabetic retinopathy (DR) have reported conflicting results. The aim of the present study was to assess the association by using meta-analysis.

Methods

A systematic search of electronic databases (PubMed, EMBASE, Elsevier Science Direct, ISI Web of Science, CBM, CNKI and VIP) was carried out until Sept 18, 2013. The pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were used to assess the strength of the association.

Results

Eleven studies (-460T/C: 6 studies including 932 cases and 722 controls; -2578C/A: 6 studies including 1,071 cases and 1,137 controls) were involved in this meta-analysis. Significant association was found for -460T/C polymorphism (C versus T: OR=1.48, 95%CI=1.07–2.05, P=0.02; TC+CC versus TT: OR=1.78, 95%CI=1.02–3.12, P=0.04; CC versus TT+TC: OR=1.76, 95%CI=1.10–2.81, P=0.02), but not for -2578C/A polymorphism (P>0.05). Similar results were found in the subgroup analysis.

Conclusions

This meta-analysis demonstrates that DR is associated with VEGF gene -460T/C polymorphism, but not -2578C/A polymorphism. Further case-control studies based on larger sample size are still needed, especially for -2578C/A polymorphism.     

Five polymorphisms of vascular endothelial growth factor (VEGF) and risk of breast cancer: a meta-analysis involving 16,703 individuals

Associations between five polymorphisms of vascular endothelial growth factor (i.e., VEGF +936C/T, −1154A/G, −2578C/A, −634G/C and −460T/C) and risk of breast cancer have been extensively studied, and the currently available results are inconclusive. Therefore, we performed this meta-analysis to further study the associations. The databases of Pubmed, Embase and CNKI were retrieved up to April 1st, 2010. The pooled ORs and 95% CIs were used to assess the strength of the associations. A total of 10 case–control studies with 8175 cases and 8528 controls were included in this study. The overall results of combined analyses showed that five polymorphisms of VEGF were not associated with risk of breast cancer [ORs (95% CIs): 1.03 (0.84–1.27) for CC vs. TT for +936C/T, 0.95 (0.81–1.12) for AA vs. GG for −1154A/G, 1.01 (0.90–1.14) for CC vs. AA for −2578C/A, 1.02 (0.90–1.16) for GG vs. CC for −634G/C and 0.86 (0.68–1.09) for TT vs. CC for −460T/C]. When subgroup analyses by ethnicity for VEGF +936C/T and −634G/C, the results suggested that +936C/T was not associated with the risk of breast cancer for either Asians [1.40 (0.92–2.13) for CC vs. TT and CC + CT vs. TT: 1.38 (0.91–2.10) for CC + CT vs. TT] or Caucasians [0.93 (0.73–1.19) for CC vs. TT and 0.91 (0.72–1.16) for CC + CT vs. TT], and −634G/C was not associated with the breast cancer for Caucasians [1.07 (0.92–1.24) for GG vs. CC and 1.05 (0.91–1.21) for GG + GC vs. CC]. In addition, when excluding one study, which was out of Hardy–Weinberg equilibrium for VEGF +963C/T and whose controls were from both patients and healthy people, the negative results were also persistent, and ORs (95% CIs) were 1.04 (0.84–1.29) for CC vs. TT, 1.03 (0.83–1.27) for (CC + CT) vs. TT. This meta-analysis suggests that the VEGF +936C/T, −1154A/G, −2578C/A, −634G/C and −460T/C may be not associated with risk of breast cancer development based on the currently available studies, especially for Caucasians. More well designed studies with larger sample size on different ethnicities are needed to further assess the associations.     

Current evidences on vascular endothelial growth factor polymorphisms and breast cancer susceptibility

Several polymorphisms of vascular endothelial growth factor (VEGF) such as 936 C/T, −2578 C/A, −406 C/T, and −1154 G/A polymorphism have been identified. Published data on the association between VEGF polymorphisms and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude OR with 95% CI was used to assess the strength of association between them. For VEGF 936C/T polymorphism, a total of 10 studies including 7,685 cases and 7,915 controls were involved in this meta-analysis. Overall, no significant associations were found between VEGF 936C/T polymorphism and breast cancer risk when all studies pooled into the meta-analysis (TC vs. CC: OR = 0.904, 95% CI = 0.797–1.024; TT vs. CC: OR = 0.974, 95% CI = 0.786–1.205; dominant model: OR = 0.911, 95% CI = 0.811–1.024; and recessive model: OR = 0.991, 95% CI = 0.801–1.226). In the subgroup analysis by ethnicity, still no significant associations were found for all comparison models. For −2578 C/A, −406 C/T, and −1154 G/A polymorphism, there were too limited data to perform a meta-analysis. In conclusion, this meta-analysis suggests that the VEGF 936C/T polymorphism may be not associated with breast cancer development. However, large sample and representative population-based studies with homogeneous breast cancer patients and well matched controls are warranted to confirm this finding.     

Association between Polymorphisms in Vascular Endothelial Growth Factor Gene and Response to Chemotherapies in Colorectal Cancer: A Meta-Analysis

BackgroundSome studies have investigated the effects of polymorphisms in the vascular endothelial growth factor (VEGF) gene on responsiveness to chemotherapy for colorectal cancer (CRC) and have shown inconclusive results.MethodsEligible studies that assessed the associations between polymorphisms in the VEGF gene and response to chemotherapy in CRC were searched in the PubMed, Embase and Medline databases until November 2014. Odds ratios (OR) and 95% confidence intervals (CIs) were used to evaluate the associations, using Review Manager software, version 5.3. Stratified analysis was also conducted.ResultsIn the overall analysis, a significant association with responsiveness to chemotherapy in CRC was identified in CC vs. CA of the VEGF -2578 C/A polymorphism (OR = 1.40, 95% CI 1.00-1.97, P = 0.05) and in CC+CT vs. TT of the VEGF -460 C/T polymorphism (OR = 0.71, 95% CI 0.53-0.96, P = 0.02). In subgroup analysis, a significant association was found in excluding anti-angiogenic agent subgroup in three comparison models of the VEGF -2578 C/A polymorphism and another three genetic models of the VEGF -460 C/T C/A polymorphism.ConclusionsCC vs. CA of the VEGF -2578 C/A polymorphism and CC+CT vs. TT of the VEGF -460 C/T polymorphism might be predictive factors of responsiveness to chemotherapy in CRC. However, single-nucleotide polymorphisms in the VEGF gene lacked sufficient predictive ability to determine whether patients with CRC should add anti-angiogenic agents to their chemotherapy regimens.     

Vascular endothelial growth factor gene polymorphisms and colorectal cancer risk: a meta-analysis

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen involved in a number of pathologic processes, including angiogenesis, tumor growth and metastasis. Polymorphisms of the VEGF gene have been associated with susceptibility to colorectal cancer (CRC). However, the specific association still remains controversial. We made a meta-analysis of the association between VEGF gene polymorphisms and CRC risk. Only eight case-control studies were retrieved, with a total of 2337 CRC patients and 2032 healthy controls. Six VEGF gene polymorphisms were addressed in all studies included, +936C>T (rs3025039), -2578C>A (rs699947), -1154G>A (rs1570360), -634G>C (rs2010963), -460C>T (rs833061), and +405C>G (rs2010963). There was a significant association between -2578C>A polymorphism and susceptibility to CRC in the comparison of C allele carriers (CC + CA) versus AA (odds ratio = 0.77, 95% confidence interval = 0.62-0.96, P = 0.02). No association was found between +936C>T, -1154G>A, -634G>C, -460C>T, and +405C>G with susceptibility to CRC. We conclude that the C allele carrier (CC + CA) of VEGF -2578C>A polymorphism appears to be a protective factor for CRC.     

MTHFR C677T polymorphism contributes to colorectal cancer susceptibility: evidence from 61 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is believed to be involved in folate metabolism which plays a critical role in carcinogenesis. To date, many case-control studies have investigated the association between MTHFR C677T polymorphism and colorectal cancer risk. However, the results were inconsistent. In order to derive a more precise estimation of the association, we conducted this meta-analysis. This meta-analysis recruited 61 published studies which were selected by a search of PubMed up to 31st September 2011, including 16,111 colorectal cancer cases and 23,192 controls. We used crude odds ratios (ORs) with 95?% confidence intervals (CIs) to assess the association between MTHFR C677T polymorphism and colorectal cancer susceptibility. Our results showed that MTHFR C667T polymorphism contributed to the decreased colorectal cancer risk in overall population (for TT vs. CC: OR?=?0.89, 95?% CI?=?0.82-0.97; for TT vs. CT/CC: OR?=?0.88, 95?% CI?=?0.83-0.92). In subgroup analysis by ethnicity, the results also indicated a correlation between the T allele of MTHFR C667T and the colorectal cancer risk in Asian population (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.69-0.97; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.74-0.90). Additionally, the correlation was also observed in male subgroup in sub-analysis by gender (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.71-0.93; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.71-0.92). In summary, our meta-analysis strongly indicated the MTHFR C667T polymorphism was associated with a reduced risk of CRC.     

VEGF +936C/T and +460C/T gene polymorphisms and oral cancer risk: a meta-analysis

Many studies have examined the association between the VEGF +936C/T (rs833061) and +460C/T (rs3025039) gene polymorphisms and oral cancer risk in various populations, but their results have been inconsistent. To assess this relationship more precisely, we performed a meta-analysis. The PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were searched for case–control studies that were published up to January 2013. Data were extracted and pooled odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated. Ultimately, six studies were included, comprising 1006 oral cancer cases and 1016 controls. Overall, the pooled OR for VEGF +936 T allele carriers (TC + TT) versus the wild-type homozygotes (CC) was 1.28 (95 % CI 1.04–1.58; P = 0.228 for heterogeneity), the pooled OR for TT versus CC was 1.64 (95 % CI 1.34–1.98; P = 0.315 for heterogeneity), and the pooled OR for the T allele versus the C allele was 1.42 (95 % CI 1.22–1.76; P = 0.286 for heterogeneity). In the stratified analysis by ethnicity, significant risks were found among Caucasians but not Asians. However, there were no associations between VEGF +460C/T and oral cancer risk in only two of the included studies. In conclusion, this meta-analysis demonstrates that the VEGF +936 T allele may be associated with an increased risk of oral cancer, especially among Caucasian populations.     

Meta-analysis demonstrates lack of association of the GSK3B −50C/T polymorphism with risk of bipolar disorder

Published data on the association between GSK3B ?50C/T (rs334558) and bipolar disorder (BD) are inconclusive. We performed this meta-analysis to evaluate the relationship of this single-nucleotide polymorphism with the susceptibility, and with the age at onset of BD. A literature search was conducted though PubMed, EMBASE, Web of Science and China National Knowledge Infrastructure databases to identify relevant studies up to February 14, 2014. We identified a total of 6 publications including 1,251 cases and 1,804 controls to investigate the effect of GSK3B ?50C/T on BD risk, and found no significant association in any genetic models (C vs. T: OR = 1.03, 95 % CI: 0.92–1.15; CC vs. TT+TC: OR = 1.04, 95 % CI: 0.84–1.28; TC+CC vs. TT: OR = 1.16, 95 % CI: 0.97–1.39; and CC vs. TC vs. TT: OR = 1.08, 95 % CI: 0.96–1.22). Subgroup analysis by ethnicity did not change the results. The association between GSK3B ?50C/T and age at onset of BD was explored by 6 identified studies with a total of 659 BD type I patients. Similarly, we did not observe significant results in any genetic models (TC+CC vs. TT: SMD = 0.20, 95 % CI: ?0.07 to 0.47; CC vs. TT+TC: SMD = 0.11, 95 % CI: ?0.10 to 0.32; CC vs. TT: SMD = 0.32, 95 % CI: ?0.13 to 0.77). The power analysis and tests for publication bias ensured the reliability of our results. In summary, this meta-analysis suggests that the functional polymorphism ?50C/T within the GSK3B gene promoter is unlikely to relate with BD risk. However, more larger and well-designed studies are still needed to yield a conclusive result on the topic.     

Update analysis of studies on the MMP-9 ?1562 C>T polymorphism and cancer risk

Polymorphisms in the matrix metalloproteinase (MMP) gene have been hypothesized to be functional and may contribute to genetic susceptibility to cancers. The common sequence variation in MMP-9 ?1562 C>T (rs3918242), has been involved in cancer risk. However, results of the related published studies were somewhat controversial and underpowered in general. To clarify the role of MMP-9 ?1562 C>T genotype in global cancer, we performed a meta-analysis of all the available published studies involving 4,124 cancer patients and 4,728 control subjects. The overall results indicated that there was no major association of the variant on cancer risk. However, stratified analysis by cancer type showed that the MMP-9 ?1562 C>T polymorphism has a lower risk in colorectal cancer (OR?=?0.80, 95%CI?=?0.66?C0.96, P _{heterogeneity}?=?0.391) and lung cancer (OR?=?0.70, 95%CI?=?0.51?C0.96, P _{heterogeneity}?=?0.959) by allelic contrast. Furthermore, association of the MMP-9 ?1562 C>T polymorphism and cancer risk was also observed in hospital-based studies under the dominant genetic model (OR?=?0.87, 95%CI?=?0.78?C0.97, P _{heterogeneity}?=?0.355), allelic contrast (OR?=?0.85, 95%CI?=?0.75?C0.96, P _{heterogeneity}?=?0.271) and heterozygote comparison (OR?=?0.89, 95%CI?=?0.79?C0.99, P _{heterogeneity}?=?0.402). This pooled analysis showed evidence that the MMP-9 ?1562 C>T polymorphism may decrease both the colorectal and lung cancer risk. Further prospective studies with larger numbers of participants worldwide are required to evaluate the association in more detail.     

Vascular endothelial growth factor (VEGF) +936 C/T gene polymorphisms and gastric cancer risk: a meta-analysis involving 4,138 subjects

The association between vascular endothelial growth factor (VEGF) +936 C/T gene polymorphisms and gastric cancer risk is still controversial and ambiguous. The objective of our study was to investigate this association. The Medline and Embase databases were searched by two investigators. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to test the association between VEGF +936 C/T polymorphisms and gastric cancer risk. Our meta-analysis comprised seven case-control studies, which included 1,893 gastric cancer cases and 2,245 controls. The combined results showed that there was no relationship between VEGF +936 C/T gene polymorphisms and gastric cancer risk (CC: OR 0.97, 95% CI 0.85, 1.11; CT: OR 1.01, 95% CI 0.88, 1.16; TT: OR 1.10, 95% CI 0.79, 1.55). Subgroup analysis by ethnicity and stage, location, and Lauren classification of gastric cancer did not change the results. This meta-analysis suggests that there is no association between VEGF +936 C/T polymorphisms and gastric cancer risk. Further studies should pay attention to other potentially functional SNPs.     

The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals

Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case–control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case–control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19–1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63–3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47–2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12–1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.     

The ?159C/T polymorphism in the CD14 gene and the risk of asthma: a meta-analysis

The -159C/T polymorphism in the CD14 gene has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study is to investigate the association between the -159C/T polymorphism in the CD14 gene and the risk of asthma by meta-analysis. We searched Pubmed, Embase, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on April 20, 2010). Statistical analysis was performed by using the softwares Revman 4.2 and STATA 10.0. A total of 17 case-control studies in 17 articles (4,246 cases and 3,631 controls) were included in this meta-analysis. There was no association between this polymorphism and asthma risk in combined analyses (odds ratio (OR)?=?0.86 and 95% confidence interval (95% CI)?=?0.72-1.02, P?=?0.09 for TC?+?TT vs. CC). In the subgroup analysis by age, ethnicity, and atopic status, no significant associations of asthma risks were obtained from age groups, ethnic groups, and atopic groups for TC?+?TT vs. CC comparison. For atopic population, significant decreased atopic asthma risks were found among Asian population (OR?=?0.69, 95% CI 0.52-0.92, P?=?0.01) and children population (OR?=?0.69, 95% CI 0.54-0.89, P?=?0.0004) for TC?+?TT vs. CC comparison. This meta-analysis suggests that CD14 is a candidate gene for atopic asthma susceptibility. The -159C/T polymorphism may be a protective factor for atopic asthma in Asian and children. More studies are needed to validate these associations.     

Polymorphisms of VEGF,TGFβ1, TGFβR2 and conotruncal heart defects in a Chinese population

Genetic variants may determine susceptibility of congenital heart disease (CHD). To evaluate the impact of transforming growth factor-β1 (TGFβ1), TGFβ receptor II (TGFβR2) and vascular endothelial growth factor (VEGF) polymorphisms on conotruncal heart defects susceptibility, we genotyped six functional polymorphisms TGFβ1 rs1800469 C>T, TGFβR2 rs3087465 G>A, VEGF ?2578C>A, ?1498T>C, ?634G>C and +936C>T in a hospital based case–control study of 244 conotruncal heart defects cases and 136 non-CHD controls in a Chinese population. Logistic regression analyses revealed that if the TGFβ1 rs1800469 CC homozygote genotype was used as the reference group, subjects carrying the CT variant heterozygote had a significant 0.48-fold decreased risk of conotruncal heart defects [odds ratio (OR) = 0.52; 95 % confidence interval (CI) = 0.30–0.88], subjects carrying the TT variant homozygote had a significant 0.47-fold decreased risk of conotruncal heart defects (OR 0.53; 95 % CI 0.28–1.00). In stratification analyses, the TGFβ1 rs1800469 C>T genotype was associated with a decreased risk for tetralogy of fallot in homozygote comparisons (OR 0.47; 95 % CI 0.22–0.99), a decreased risk for transposition of great artery in the dominant genetic model (OR 0.49; 95 % CI 0.28–0.87) and heterozygote comparisons (OR 0.45; 95 % CI 0.24–0.83). Our findings suggest that TGFβ1 rs1800469 C>T polymorphism was significantly associated with decreased risk of conotruncal heart defects. TGFβR2 rs3087465 G>A, VEGF ?2578C>A, ?1498T>C, ?634G>C and +936C>T polymorphisms may not play a role in the susceptibility of conotruncal heart defects.     

Association between the −1438G/A and T102C polymorphisms of 5-HT2A receptor gene and obstructive sleep apnea: a meta-analysis

The serotonin 2A (5-HT2A) receptor has been implicated in obstructive sleep apnea (OSA). Single nucleotide polymorphisms (SNPs) in the 5-HT2A gene have been found in OSA, the most common being ?1438G/A and T102C; however, studies of the association between 5-HT2A SNPs and OSA risk have reported inconsistent findings. A meta-analysis was performed to quantitatively review the association between ?1438G/A and T102C SNPs and OSA. Five studies, including 791 subjects for ?1438G/A genotype and 1,068 subjects for T102C genotype, were selected. Pooled data analysis of the ?1438G/A genotype indicated a significantly increased OSA risk was associated with two variant genotypes (AA vs. AG+GG: OR 3.023, 95 % CI 2.169–4.213, P = 0.506 for heterogeneity; A allele carriers vs. GG: OR 1.938, 95 % CI 0.879–4.274, P = 0.012 for heterogeneity). Stratification analysis by gender supported the association in males, but not females. For the T102C genotype, no significantly increased OSA risk was associated with the two variant genotypes (CC vs. CT+TT: OR 1.065, 95 % CI 0.787–1.442, P = 0.361 for heterogeneity; C allele carriers vs. TT: OR 0.979, 95 % CI 0.737–1.3, P = 0.9 for heterogeneity).In conclusions, meta-analysis indicated that the ?1438G/A, and not T102C, polymorphism of 5-HT2A is a positive risk factor of OSA, especially in males.     

Vascular endothelial growth factor and recurrent spontaneous abortion: A meta-analysis

To evaluate the association between vascular endothelial growth factor (VEGF) gene polymorphisms and the risk of recurrent spontaneous abortion (RSA), a meta-analysis of published case–control studies for the VEGF gene polymorphisms (gene polymorphisms reported more than three times were selected) and the risk of RSA. Odds ratios (ORs) and 95% confidence intervals (CIs) for codominant, dominant and recessive genetic models were assessed by RevMan software. Eight studies with 2813 cases and 2830 controls were included in this meta-analysis. The pooled analysis showed that − 2578C/A, − 1154G/A polymorphisms of VEGF were not significantly associated with the risk of RSA neither under codominant model nor under dominant model, nor under recessive model. Whereas, for − 634G/C polymorphism, the pooled OR and 95% CI were 1.23 (1.01–1.49) under recessive model; and for 936C/T polymorphism, the pooled OR and 95% CI were 1.34 (1.07–1.67) and 1.40 (1.09–1.80) under codominant and dominant models, respectively. This meta-analysis suggested that VEGF gene − 2578C/A, − 1154G/A polymorphisms were not significantly associated with the risk of RSA, whereas, − 634G/C and + 936C/T polymorphisms were associated with the risk of RSA under specific genetic models.     

Association of -619C/T polymorphism in CDSN gene and psoriasis risk: a meta-analysis

Previous studies investigating the association between corneodesmosin (CDSN) polymorphisms and psoriasis risk have provided inconsistent results. The aim of our study was to clarify the effects of CDSN -619C/T polymorphism on psoriasis risk by conducting a meta-analysis. We conducted searches of the published literature in Pubmed and Embase databases up to October 2010. Six studies with a total of 842 psoriasis cases and 981 healthy controls were retrieved. Statistical analysis was performed with the programs Review Manager (version 5.0.24) and Stata (version 9.2). Meta-analysis results showed that there was no significant difference in CDSN -619C/T genotype distribution between psoriasis and control in the comparisons of C allele vs T allele, CC vs CT + TT, CC + CT vs TT, CC vs TT, and CC vs CT (respectively: OR = 1.28, 95%CI = 0.82-2.00, P = 0.28; OR = 1.33, 95%CI = 0.80-2.21, P = 0.28; OR = 1.23, 95%CI = 0.80-1.91, P = 0.35; OR = 1.41, 95%CI = 0.64-3.12, P = 0.40; OR = 1.30, 95%CI = 0.81-2.06, P = 0.27). In the subgroup analysis by ethnicity, results also showed no significant association between CDSN -619C/T polymorphism and susceptibility to psoriasis in both Caucasian and Asian populations. In conclusion, this meta-analysis suggests that CDSN -619C/T polymorphism may not be associated with susceptibility to psoriasis.     

miR-196a2 C allele is a low-penetrant risk factor for cancer development

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR=1.23, 95% CI=1.11-1.36; CC vs. TT: OR=1.30, 95% CI=1.14-1.48; dominant model: OR=1.25, 95% CI=1.13-1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR=1.24, 95% CI=1.10-1.40; CC vs. TT: OR=1.31, 95% CI=1.13-1.52; dominant model: OR=1.26, 95% CI=1.12-1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR=1.15, 95% CI=1.00-1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR=1.15, 95% CI=1.01-1.31; CC vs. TT: OR=1.30, 95% CI=1.01-1.68; dominant model: OR=1.22, 95% CI=1.00-1.50; and recessive model: OR=1.11, 95% CI=1.01-1.23) and lung cancer (CC vs. TT: OR=1.30, 95% CI=1.10-1.54; and recessive model: OR=1.18, 95% CI=1.02-1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR=1.30, 95% CI=1.13-1.49; CC vs. TT: OR=1.37, 95% CI=1.14-1.66; dominant model: OR=1.32, 95% CI=1.15-1.53) and population-based studies (CC vs. TT: OR=1.19, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.01-1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.     

Association between polymorphisms in the promoter region of interleukin-10 and susceptibility to inflammatory bowel disease

The aim of this study was to assess the association of polymorphisms in the promoter region of the IL-10 gene with the risk of inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC). Fifteen studies (3,693 cases and 4,574 controls) were included in a meta-analysis of association between IL-10 ?1082G/A, ?819C/T and ?592C/A polymorphisms, and IBD, CD and UC using allele contrast and the recessive, dominant, and additive models. Hardy–Weinberg equilibrium was confirmed for each study. Heterogeneity and study quality were investigated using stratification analyses and sensitivity analyses. Polymorphism ?1082G/A showed significant association with CD, with odds ratios (ORs) for the GG + GA genotype and GG versus AA genotype of 1.278 (1.004–1.627) and 1.238 (1.027–1.492) in all subjects. Significant associations were found in the Caucasian subgroup using the allele contrast, dominant, and additive models. C-allele carriers of the ?819C/T polymorphism were at increased risk of IBD (OR 1.093, 95 % CI 1.004–1.190). Association with the ?819C/T polymorphism was also found in Caucasians with CD (C vs. T: OR 1.104, 95 % CI 1.010–1.206; CC + CT vs. TT: OR 1.328, 95 % CI 1.006–1.754; CC vs. TT: OR 1.339, 95 % CI 1.008–1.778), and with UC (CC vs. CT + TT: OR 1.188, 95 % CI 1.019–1.385). No significant association was found between the ?592C/A polymorphism and IBD, CD or UC. In conclusion, the meta-analysis demonstrated clear association between the IL-10 polymorphisms ?1082G/A and ?819C/T and the risk of IBD.     

RNASEL Asp541Glu and Arg462Gln polymorphisms in prostate cancer risk: evidences from a meta-analysis

Epidemiological studies have evaluated the association between RNASEL Asp541Glu and Arg462Gln polymorphisms and prostate cancer (PCa) risk. However, the results remain inconclusive. To derive a more precise estimation of the association between RNASEL polymorphisms and PCa risk, we performed a meta-analysis based on nineteen case?Ccontrol studies. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, we found that both Asp541Glu and Arg462Gln polymorphisms were not associated with PCa risk (for Asp541Glu polymorphism: Glu/Glu vs. Asp/Asp: OR 1.17, 95% CI: 0.95?C1.45, P?=?0.13; Glu/Asp vs. Asp/Asp: OR 1.02, 95% CI: 0.92?C1.14, P?=?0.70; for Arg462Gln polymorphism: Gln/Gln vs. Arg/Arg: OR 0.98, 95% CI: 0.88?C1.08, P?=?0.62; Gln/Arg vs. Arg/Arg: OR 0.97, 95% CI: 0.91?C1.04, P?=?0.53). The insignificant association was maintained in the dominant and the recessive genetic models. In subgroup analyses, the significant association was not detected in Caucasian populations. However, we found the significant association of RNASEL Asp541Glu polymorphism with sporadic PCa (Glu/Glu vs. Asp/Asp: OR 1.29, 95% CI: 1.04?C1.59, P?=?0.02; Glu/Asp vs. Asp/Asp: OR 1.24, 95% CI: 1.03?C1.50, P?=?0.03). In conclusion, we found that these RNASEL polymorphisms were not related to overall PCa risk, especially in Caucasians. However, in subgroup analyses we found a suggestion that RNASEL 541Gln allele might be a low-penetrent risk factor for sporadic PCa.