The association between common genetic variant of microRNA-146a and cancer susceptibility

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.     

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.     

Correlation between TGF-β1-509 C>T polymorphism and risk of digestive tract cancer in a meta-analysis for 21,196 participants

The association between transforming growth factor β1 (TGF-β1)-509 C>T and risk of digestive tract cancer (DTC) remained uncertain as previous studies reported conflicting results. The aim of this study was to assess the association by using a meta-analysis. The databases of MEDLINE, EMBASE and WANGFANG (Chinese database) were retrieved, and latest update was on 2nd February, 2012. Pooled odds ratio and 95% confidence interval (OR and 95% CI) were calculated by using a fixed- or random-effect model. Ultimately, twenty nine case-control studies with 8664 cases and 12,532 controls were included in this meta-analysis. Overall, there was no association between TGF-β1-509 C>T and risk of DTC in all genetic comparison models (OR and 95% CI: 0.96 and 0.81-1.15 for TT vs. CC, 0.98 and 0.91-1.05 for T carriers vs. C carriers). When subgroup analyses were conducted according to ethnicity, types of cancer and sample size, T allele was significantly associated with decreased risk of DTC for Caucasians and for large sample-sized studies, and was associated with decreased risk of colorectal cancer (OR and 95% CI for TT vs. CC: 0.82 and 0.70-0.97 for Caucasians, 0.80 and 0.68-0.98 for large sample-sized studies, 0.78 and 0.62-0.97 for colorectal cancer). This study indicated that TGF-β1-509 C>T polymorphism was probably associated with risk of DTC, especially for Caucasians. Because of modest limitation, our findings should be confirmed by future studies.     

Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: A meta-analysis based on 14 case-control studies

Interleukin-10 (IL-10) has been described as an anti-inflammatory cytokine and IL-10 gene polymorphisms was associated with altered interleukin-10 levels, therefore, we aimed to conduct a meta-analysis assessing the association of IL-10 genetic polymorphisms with the risk of both chronic periodontitis (CP) and aggressive periodontitis (AgP). Electronic databases were acquired from PubMed, Embase, the Sinomed and WANFANG. Fourteen studies with 1438 patients and 1303 control subjects investigated the association of the three single-nucleotide polymorphisms (SNPs) of IL-10 (-1082A>G, -819C>T, -592C>A) and chronic/aggressive periodontitis risk were brought into this study. We found that there was no association between IL-10 -1082 gene polymorphism and periodontitis risk (either CP or AgP), even when we separately investigated sub-group analysis among Caucasians. The -819 polymorphism seemed to be a genetic risk factor to CP among Caucasians (T allele vs. C allele: OR=1.55, 95%CI=1.07-2.24; CT vs. CC: OR=1.64, 95%CI=1.00-2.67). When excluding one study deviated from HWE, the results showed that the T allele carriers had a significantly risk of CP in overall population (T allele vs. C allele: OR=1.23, 95%CI=1.03-1.48). Furthermore, the results of this meta-analysis showed that -592 polymorphism was associated with a significantly increased risk of CP (A allele vs. C allele: OR=1.38, 95%CI=1.04-1.85; AA vs. CA+CC: OR=1.39, 95%CI=1.05-1.85 for overall analysis; A allele vs. C allele: OR=1.97, 95%CI=1.36-3.86; AA vs. CC: OR=3.70, 95%CI=1.32-10.39; CA vs. CC: OR=2.22, 95%CI=1.36-3.64, AA+CA vs. CC: OR=2.35, 95%CI=1.46-3.79 for Caucasian descent analysis). This meta-analysis suggested that IL-10 -819 and -592 gene polymorphisms were associated with CP, especially among Caucasians. Further research is needed to assess possible gene-gene or gene-environment-lifestyle interactions on periodontal disease..     

CDH1 -160C>A gene polymorphism is an ethnicity-dependent risk factor for gastric cancer

The associations between E-cadherin (CDH1) gene polymorphisms and gastric cancer (GC) susceptibility are still controversial. Given this uncertainty, we carried out a meta-analysis of published case-control studies to derive more precise estimations of these relationships. Relevant studies were identified from PubMed and EMBASE up to March 2011. Seventeen studies with 3511 GC cases and 4826 controls were selected. Crude odds ratios (OR) and 95% confidence intervals (CI) were used to investigate the strength of the associations. No associations between CDH1 (+54T>C, -160C>A, -347G>GA, -616G>C, -2076C>T and -3159T>C) gene polymorphisms and GC risk for all genetic models were found. As for CDH1 -160C>A polymorphism, subgroup analyses by country, gender, study design, smoking status, Helicobacter pylori infection, and the Lauren classification of GC did not change the results. When stratified by ethnicity, we found the A allele carriers had a significantly increased risk of GC among Caucasians (AA vs. CA+CC: OR=1.50, 95% CI=1.03-2.19, P=0.03), but not among Asians (AA vs. CA+CC: OR=0.87, 95% CI=0.56-1.37, P=0.56). No publication bias was found in the present study. This meta-analysis suggests that CDH1 -160C>A gene polymorphism may contribute to increased risk of GC among Caucasians.     

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.     

Interleukin-4 rs2243250 polymorphism is associated with asthma among Caucasians and related to atopic asthma

Published data on the association between interleukin-4 (IL-4) rs2243250 (C-589T) polymorphism and asthma susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies with 3037 asthma patients and 3032 healthy controls were included. Overall, significantly elevated asthma risk was associated with IL-4 T allele when all studies were pooled into the meta-analysis (CT vs. CC: OR=1.187, 95% CI=1.016-1.387; dominant model: OR=1.213, 95% CI=1.046-1.405). In the subgroup analysis by ethnicity, significantly increased risk was only found for Caucasians (TT vs. CC: OR=1.591, 95% CI=1.032-2.452; dominant model: OR=1.292, 95% CI=1.028-1.624). When stratified by asthma type, statistically significantly elevated risk was only found in atopic asthma group (dominant model: OR=1.313, 95% CI=1.033-1.667). Despite some limitations, this meta-analysis suggests that T allele at position -589 of the IL-4 gene promoter region is a low-penetrant risk factor for asthma development especially for Caucasians and atopic type.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

Lack of association between methylenetetrahydrofolate reductase gene A1298C polymorphism and breast cancer susceptibility

Published data on the association between methylenetetrahydrofolate reductase gene (MTHFR) A1298C polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Medline, PubMed, Embase, and Web of Science were searched. Crude ORs with 95% CIs were used to assess the strength of association between the MTHFR A1298C polymorphism and breast cancer risk. The pooled ORs were performed for co-dominant model (AC vs. AA, CC vs. AA), dominant model (CC+AC vs. AA), and recessive model (CC vs. AC+AA), respectively. A total of 26 studies including 12,244 cases and 15,873 controls were involved in this meta-analysis. Overall, no significant associations were found between MTHFR A1298C polymorphism and breast cancer risk when all studies pooled into the meta-analysis (AC vs. AA: OR=0.99, 95% CI 0.94-1.05; CC vs. AA: OR 0.99, 95% CI 0.90-1.09; dominant model: OR=0.99, 95% CI 0.95-1.04; and recessive model: OR=0.98, 95% CI 0.90-1.08). In the subgroup analysis by ethnicity or study design, still no significant associations were found for all comparison models. In conclusion, this meta-analysis suggests that the MTHFR A1298C 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 of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.     

The Association between Two MicroRNA Variants (miR-499, miR-149) and Gastrointestinal Cancer Risk: A Meta-Analysis

Background

MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Single nucleotide polymorphisms (SNPs) in miRNAs may contribute to cancer susceptibility due to changes in the microRNA’s properties and/or maturation. The present study aimed to investigate the association between two miRNA polymorphisms (miR-499 rs3746444 and miR-149 rs2292832) and gastrointestinal (GI) cancer risk.

Methodology/Principal Findings

We conducted a search of case-control studies in PubMed, Wiley Online Library, Web of Science and the CNKI database. Eleven rs3746444 studies and six rs2292832 studies were included in our meta-analysis. The only obvious association between the miR-499 polymorphism and colorectal cancer susceptibility was found in the homozygote comparison (GG vs. AA: OR = 1.66, 95% CI: 1.02–2.70, P _h = 0.10, P = 0.04). No significant association was found in the subgroup analysis for ethnicity and risk of hepatocellular and gastric cancer. A marginally elevated GI cancer risk was discovered in the recessive model for miR-149 (TT vs. TC+CC: OR = 1.15, 95% CI: 1.03–1.30, P _h = 0.68, P = 0.02). Stratifying the results by ethnicity revealed a slight association between the recessive model and the Asian population (TT vs. TC+CC: OR = 1.14, 95% CI: 1.01–1.29, P _h = 0.79, P = 0.03).

Conclusions/Significance

The present meta-analysis indicates that miR-499 may be associated with the risk to colorectal cancer. MiR-149 may confer a marginally increased risk of susceptibility to gastrointestinal cancer, especially for Asians.     

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 -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.     

No association between IL-1β -511 C/T polymorphism and the risk of duodenal ulcer: A meta-analysis of 4667 subjects

Epidemiological studies have evaluated the association between IL-1β -511 C/T polymorphism and duodenal ulcer (DU) risk. However, the results remain conflicting. The aim of this study was to perform a meta-analysis to investigate a more authentic association between IL-1β -511 C/T polymorphism and DU. Systematic searches of electronic databases Embase, PubMed and Web of Science as well as hand searching of the references of identified articles and the meeting abstracts were performed. Study selection, data abstraction and study quality evaluation were independently conducted in duplicate. Statistical analyses were performed using software Stata 11.0. The pooled odds ratios (ORs) with 95% confidence intervals (95% CIs) were performed. Publication bias was tested by Begg's funnel plot and Egger's regression test. A total of 14 studies including 1887 cases and 2780 controls were included in our final meta-analysis. There was no evidence of significant association between IL-1β -511 C/T polymorphism and DU (for T allele vs. C allele: OR=0.93, 95% CI=0.82-1.06; for T/T vs. C/C: OR=0.83, 95% CI=0.64-1.08; for dominant model: OR=0.93, 95% CI=0.80-1.07; and for recessive model: OR=0.87, 95% CI=0.69-1.11). Significant association was found in all genetic models for the PB subgroup and sensitivity analyses. In conclusion, our meta-analysis suggests that there was no evidence of a significant association between IL-1β -511 C/T polymorphism and DU with or without Helicobacter pylori infection, whereas a significant association was found by sensitivity analyses which showed a protective effect of the T allele against DU risk.     

Association between CASP3 polymorphisms and overall cancer risk: A meta-analysis of case-control studies

Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.     

Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and acute rejection risk in transplant recipients

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene polymorphisms have been reported to influence the risk for acute rejection (AR) in transplant recipients. However, the results still remain controversial and ambiguous. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of AR in transplant recipients. Electronic searches for all publications were conducted on associations between this variant and acute rejection in Medline and Embase databases through November 2011. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 18 case-control studies from ten articles were analyzed. This meta-analysis included 2,081 cases of transplant recipients in which 813 cases developed AR and 1,268 cases did not develop AR. The results indicated that there was no statistically significant association between the risk of AR and the +49A/G polymorphism or the -318C/T polymorphism (+49A/G: OR = 0.876, 95 % CI = 0.650-1.180 for GG vs. AA; OR = 1.121, 95 % CI = 0.911-1.379 for AG + GG vs. AA; -318C/T: OR = 0.397, 95 % CI = 0.138-1.143 for TT vs. CC; OR = 0.987, 95 %CI = 0.553-1.760 for CT + TT vs. CC). However, individuals who carried CT60 A allele might have a decreased risk of AR (AA vs. GG OR = 0.535, 95 % CI = 0.340-0.841, A vs. G OR = 0.759, 95 % CI = 0.612-0.914) in liver transplant recipients among Europeans, but because only two studies were included, so the result should be caution. In further stratified analyses for the +49A/G and the -318C/T polymorphisms, no obvious significant associations were found in subgroups of renal transplant recipients and Europeans, a reduced incidence of acute rejection was observed in liver transplant recipients that are homogenous for +49G (OR = 0.638, 95 % CI = 0.427-0.954 for GG vs. AA/AG), while this has not been observed in renal transplant recipients. Overall this meta-analysis suggests that +49A/G and the -318C/T polymorphisms in CTLA-4 may be not associated with the risk of rejection after organ transplantation, but CTLA +49A/G and +6230G/A polymorphisms may be associated with acute rejection after liver transplantation, not after renal transplantation. In future, more studies should be included to evaluate the association between +6230G/A polymorphism and AR risk.     

The E-cadherin (CDH1) -160C>A polymorphism associated with gastric cancer among Asians but not Europeans

E-cadherin (CDH1) is a tumor suppressor gene involved in epithelial cell-cell interactions and plays important roles in the etiology of gastric cancer. Studies reporting conflicting results on the role of -160C>A polymorphism in the CDH1 promoter region on gastric cancer risk led us to perform a meta-analysis to investigate this relationship. Thirteen published case-control studies including 2509 gastric cancer cases and 3687 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. Overall, individuals with the variant genotypes were not associated with a significant gastric cancer risk (AA vs. CC: OR?=?1.04, 95% CI: 0.74-1.48; CA vs. CC: 1.02, 0.85-1.21; AA/CA vs. CC: 1.03, 0.86-1.22; AA vs. CA/CC: 1.03, 0.74-1.43). However, in the stratified analysis by ethnicity, significantly decreased gastric cancer risk was found among Asians in dominant model (AA/CA vs. CC: 0.84, 0.72-0.99). Further, when stratified by clinicopathologic characteristics of gastric cancer, no statistically significant result was observed for any analysis. The results suggested that the CDH1 -160C>A polymorphism may contribute to susceptibility to gastric cancer among Asians. Additional well-designed large studies will be required to validate this association in different populations.     

Association between the G-protein β3 subunit C825T polymorphism with essential hypertension: a meta-analysis in Han Chinese population

We aimed to evaluate the contribution of the G-protein β3 subunit C825T (GNB3-C825T) polymorphism to essential hypertension (EH) in Han Chinese population by performing meta-analysis. A meta-analysis was performed in 12 case-control genetic association studies including 3,020 hypertension patients and 2,790 controls from MEDLINE (PubMed) and the China National Knowledge Infrastructure platforms. The STATA 10.0 software was used in analysis. Overall, there was no significant association between the GNB3-C825T polymorphism and EH in neither additive [TT vs. CC: OR (95 % CI) = 1.11 (0.74-1.69), P = 0.61; TC vs. CC: OR (95 % CI) = 1.08 (0.89-1.31), P = 0.42], nor dominant [TT + TC vs. CC: OR (95 % CI) = 1.11 (0.86-1.42), P = 0.43] and nor recessive [TT vs. TC + CC: OR (95 % CI) = 1.04 (0.75-1.44), P = 0.81] genetic models. Although further subgroup analysis found statistically significant results [T vs. C: OR (95 % CI) = 1.50 (1.05-2.15), P = 0.03] in the southern population, but after exclusion one particular study, the significant association was disappeared. No significant result was found in the northern Han Chinese population. There was no significant association identified between GNB3-C825T polymorphism and EH in Han Chinese population. Further larger sample and well-designed studies are needed to assess the genetic association particularly in the southern Han Chinese population.     

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

Background

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

Methodology/Principal Findings

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

Conclusions

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