A functional +61G/A polymorphism in epidermal growth factor is associated with glioma risk among Asians

Background

Epidermal growth factor (EGF), a potent mitogenic protein, plays an important role in the development of cancers, including glioma. Previous studies showed that the EGF +61G/A polymorphism (rs4444903) may lead to an alteration in EGF production and/or activity, which can result in individual susceptibility to glioma. However, published data regarding the association between the +61G/A polymorphism and glioma risk was contradictory.

Objective

The aim of this study was to perform a meta-analysis of eligible studies to derive precise estimation of the association of EGF +61G/A with glioma risk.

Methods

We performed a pooled analysis of seven published studies that included 1,613 glioma cases and 2,267 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association. The pooled ORs were performed for codominant model, dominant model, and recessive model, respectively.

Results

Overall, no significant associations between the EGF +61G/A polymorphism and glioma cancer risk were found for AA versus GG (OR = 0.95, 95% CI = 0.62–1.45), GA versus GG (OR = 0.94, 95% CI = 0.72–1.22), AA/GA versus GG (OR = 0.93, 95% CI = 0.70–1.23), and AA versus GA/GG (OR = 1.04, 95% CI = 0.77–1.39). However, in the stratified analysis by ethnicity, the EGF +61G/A polymorphism had a higher risk of glioma development among Asians, but a lower risk among Caucasians.

Conclusions

Taken together, the results suggest that the EGF +61G/A polymorphism may contribute to the susceptibility of glioma in different ethnic groups.     

Association between CD209 -336A/G and -871A/G Polymorphisms and Susceptibility of Tuberculosis: A Meta-Analysis

Background

The association between CD209 promoter polymorphisms (-336A/G, -871A/G) and tuberculosis (TB) risk has been widely reported, but results of previous studies remain controversial and ambiguous. To assess the association between CD209 polymorphisms and TB risk, a meta-analysis was performed.

Methods

Based on comprehensive searches of the PubMed, Embase, Web of Science, Weipu, and CBM databases, we identified outcome data from all articles estimating the association between CD209 polymorphisms and TB risk. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated.

Results

A total of 14 studies with 3,610 cases and 3,539 controls were identified. There was no significant association between CD209 -336A/G polymorphism and TB risk (OR = 1.04, 95% CI = 0.91–1.19 for G vs. A; OR = 1.13, 95% CI = 0.84–1.53 for GG vs. AA; OR = 1.04, 95% CI = 0.87–1.24 for GG+AG vs. AA; OR = 1.11, 95% CI = 0.88–1.39 for GG vs. AG+AA). However, the significant association was revealed for Asians in GG vs. AA (OR = 2.48, 95% CI = 1.46–4.22, P = 0.0008) and GG vs. AG+AA (OR = 2.10, 95% CI = 1.33–3.32, P = 0.001). For the CD209 -871A/G polymorphism, lack of an association was also found (OR = 0.81, 95% CI = 0.70–0.95 for G vs. A; OR = 1.00, 95% CI = 0.52–1.93 for GG vs. AA; OR = 0.73, 95% CI = 0.60–0.89 for GG+AG vs. AA; OR = 1.09, 95% CI = 0.57–2.10 for GG vs. AG+AA).

Conclusion

The present meta-analysis suggested that CD209 promoter polymorphisms (-336A/G, -871A/G) were unlikely to substantially contribute to TB susceptibility. However, the GG genotype of CD209 -336A/G polymorphism might be a genetic risk factor that increases TB susceptibility for Asians in GG vs. AA and GG vs. AG+AA.     

The -2518A/G Polymorphism in the MCP-1 Gene and Tuberculosis Risk: A Meta-Analysis

Background

The -2518A/G polymorphism in the monocyte chemoattractant protein-1 (MCP-1) gene has been implicated in the susceptibility to tuberculosis (TB), but the results are not conclusive. The aim of this study is to investigate the association between the -2518A/G polymorphism in the MCP-1 gene and the risk of tuberculosis by meta-analysis.

Methods

We searched Pubmed, Embase, CNKI and Wanfang databases, covering all studies until April 29^th, 2011. Statistical analyses were performed using the Revman4.2 and STATA10.0 software.

Results

A total of 5341 cases and 6075 controls in 13 case-control studies were included in the meta-analysis. The results indicated that the GG homozygote carriers had a 67% increased risk of TB compared with the A allele carriers (GG vs. GA+AA: OR = 1.67, 95%CI = 1.25–2.23, P = 0.0006). In the subgroup analysis by ethnicity, significant elevated risks were found in Asians and Latinos, but not in Africans (GG vs. GA+AA: OR = 1.79, 95%CI = 1.19–2.70 and P = 0.005 for Asians; OR = 2.15, 95%CI = 1.32–3.51 and P = 0.002 for Latinos; OR = 1.28, 95%CI = 0.45–3.64 and P = 0.65 for Africans).

Conclusion

This meta-analysis suggested that the -2518A/G polymorphism of MCP-1 gene would be a risk factor for TB in Asians and Latinos, while not in Africans.     

Increased risk of breast cancer associated with CC genotype of Has-miR-146a Rs2910164 polymorphism in Europeans

Background

Emerging evidence suggests that microRNAs play a critical role in the pathogenesis of breast cancer. Several molecular epidemiological studies were conducted in recent years to evaluate the association between has-miR-146a rs2910164 polymorphism and breast cancer risk in diverse populations. However, the results remain conflicting rather than conclusive.

Methodology/Principal findings

We performed a meta-analysis of 6 case-control studies that included 4238 breast-cancer cases and 4469 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, this meta-analysis showed that the rs2910164 polymorphism was not associated with a significantly increased risk of breast cancer in all genetic models (for GC vs GG: OR = 1.00, 95% CI = 0.90−1.09, P _{heterpgeneity} = 0.364; for CC vs GG: OR = 1.16, 95% CI = 0.98−1.36, P _{heterpgeneity} = 0.757; for GC+CC vs GG: OR = 1.02, 95% CI = 0.93−1.12, P _{heterpgeneity} = 0.562; for CC vs GC+GG: OR = 1.10, 95% CI = 0.96−1.26, P _{heterpgeneity} = 0.441). However, in the stratified analysis by ethnicity, we found the rs2910164 polymorphism was associated with increased breast cancer risk among Europeans in homozygote comparison (CC vs. GG: OR = 1.29, 95%CI = 1.02−1.63, P _{heterpgeneity} = 0.950, P = 0.032) and recessive model (CC vs. GC+GG: OR = 1.31, 95%CI = 1.05−1.65, P _{heterpgeneity} = 0.839, P = 0.019). No publication bias was found in the present study.

Conclusions/Significance

This meta-analysis suggests, for the first time, that the CC homozygote of rs2910164 may contribute to breast cancer susceptibility in Europeans.     

Hsa-miR-196a2 Rs11614913 polymorphism contributes to cancer susceptibility: evidence from 15 case-control studies

Background

MicroRNAs (miRNAs) are a family of endogenous, small and noncoding RNAs that negatively regulate gene expression by suppressing translation or degrading mRNAs. Recently, many studies investigated the association between hsa-miR-196a2 rs11614913 polymorphism and cancer risk, which showed inconclusive results.

Methodology/Principal Findings

We conducted a meta-analysis of 15 studies that included 9,341 cancer cases and 10,569 case-free controls. We assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, individuals with the TC/CC genotypes were associated with higher cancer risk than those with the TT genotype (OR = 1.18, 95% CI = 1.03–1.34, P<0.001 for heterogeneity test). In the stratified analyses, we observed that the CC genotype might modulate breast cancer risk (OR = 1.11, 95%CI = 1.01–1.23, P _{heterogeneity} = 0.210) and lung cancer risk (OR = 1.25, 95%CI = 1.06–1.46, P _{heterogeneity} = 0.958), comparing with the TC/TT genotype. Moreover, a significantly increased risk was found among Asian populations in a dominant model (TC/CC versus TT, OR = 1.24, 95% CI = 1.07–1.43, P _{heterogeneity} = 0.006).

Conclusions

These findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers.     

Tumor Necrosis Factor Alpha rs1800629 Polymorphism and Risk of Cervical Lesions: A Meta-Analysis

Background

Tumor necrosis factor- alpha (TNF-α) is an inflammatory cytokine which may play important role on the immune response may control the progression of cervical lesions. There is a possible association between TNF-α rs1800629 G/A polymorphism and cervical lesions, but previous studies report conflicting results. We performed a meta-analysis to comprehensively assess the association between TNF-α rs1800629 polymorphism and cervical lesions risk.

Methods

Literature searches of Pubmed, Embase, Web of Science, and Wanfang databases were performed for all publications on the association between TNF-α rs1800629 polymorphism and cervical lesions through December 15, 2012. The pooled odds ratios (ORs) with their 95% confidence interval (95%CIs) were calculated to assess the strength of the association.

Results

Twenty individual case-control studies from 19 publications with a total of 4,146 cases and 4,731 controls were finally included into the meta-analysis. Overall, TNF-α rs1800629 polymorphism was significantly associated with increased risk of cervical lesions under two main genetic comparison models (For A versus G: OR 1.22, 95%CI 1.04–1.44, P = 0.017; for AA versus GG: OR 1.32, 95%CI 1.02–1.71, P = 0.034). Subgroup analysis by ethnicity further showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical lesions in Caucasians but not in Asians. Subgroup analysis by the types of cervical lesions showed that there was a significant association between TNF-α rs1800629 polymorphism and increased risk of cervical cancer (For A versus G: OR 1.24, 95%CI 1.05–1.47, P = 0.011; for AA versus GG: OR 1.31, 95%CI 1.01–1.70, P = 0.043; for AA/GA versus GG: OR 1.25, 95%CI 1.01–1.54, P = 0.039).

Conclusion

The meta-analysis suggests that TNF-α rs1800629 polymorphism is associated with increased risk of cervical lesions, especially in Caucasians.     

A genetic variant in miR-196a2 increased digestive system cancer risks: a meta-analysis of 15 case-control studies

Background

MicroRNAs (miRNAs) negatively regulate the gene expression and act as tumor suppressors or oncogenes in oncogenesis. The association between single nucleotide polymorphism (SNP) in miR-196a2 rs11614913 and the susceptibility of digestive system cancers was inconsistent in previous studies.

Methodology/Principal Findings

An updated meta-analysis based on 15 independent case-control studies consisting of 4999 cancer patients and 7606 controls was performed to address this association. It was found that miR-196a2 polymorphism significantly elevated the risks of digestive system cancers (CT vs. TT, OR = 1.25, 95% CI = 1.07–1.45; CC vs. TT, OR = 1.38, 95% CI = 1.13–1.67; CC/CT vs. TT, OR = 1.29, 95% CI = 1.10–1.50; CC vs. CT/TT, OR = 1.14, 95% CI = 1.01–1.30; C vs. T, OR = 1.15, 95% CI = 1.05–1.26). We also found that variant in miR-196a2 increased the susceptibility of colorectal cancer (CRC) (CT vs. TT, OR = 1.23, 95% CI = 1.04–1.44; CC vs. TT, OR = 1.32, 95% CI = 1.08–1.61; CC/CT vs. TT, OR = 1.25, 95% CI = 1.07–1.46; C vs. T, OR = 1.15, 95% CI = 1.05–1.28), while the association in recessive model (CC vs. CT/TT, OR = 1.16, 95% CI = 0.98–1.38) showed a marginal significance. Additionally, significant association between miR-196a2 polymorphism and increased risk of hepatocellular cancer (HCC) was detected. By stratifying tumors on the basis of site of origin, source of controls, ethnicity and allele frequency in controls, elevated cancer risks were observed.

Conclusion/Significance

Our findings suggest the significant association between miR-196a2 polymorphism and increased susceptibility of digestive system cancers, especially of CRC, HCC and Asians. Besides, C allele may contribute to increased digestive cancer risks.     

Lack of association of SULT1A1 R213H polymorphism with colorectal cancer: a meta-analysis

Background

A number of case-control studies were conducted to investigate the association of SULT1A1 R213H polymorphisms with colorectal cancer (CRC) in humans. But the results were not always consistent. We performed a meta-analysis to examine the association between the SULT1A1 R213H polymorphism and CRC.

Methods and Findings

Data were collected from the following electronic databases: PubMed, Elsevier Science Direct, Excerpta Medica Database, and Chinese Biomedical Literature Database, with the last report up to September 2010. A total of 12 studies including 3,549 cases and 5,610 controls based on the search criteria were involved in this meta-analysis. Overall, no significant association of this polymorphism with CRC was found (H versus R: OR = 1.04, 95%CI = 0.94–1.16, P = 0.46; HR+HH versus RR: OR = 1.01, 95%CI = 0.92–1.11, P = 0.81; HH versus RR+HR: OR = 1.01, 95%CI = 0.74–1.38, P = 0.95; HH versus RR: OR = 1.00, 95%CI = 0.77–1.31, P = 0.98; HR versus RR: OR = 1.01, 95%CI = 0.92–1.11, P = 0.86). In subgroup analysis, we also did not find any significant association in Cauasians (H versus R: OR = 1.02, 95%CI = 0.92–1.15, P = 0.68; HR+HH versus RR: OR = 0.99, 95%CI = 0.91–1.09, P = 0.90; HH versus RR+HR: OR = 1.01, 95%CI = 0.73–1.39, P = 0.97; HH versus RR: OR = 0.99, 95%CI = 0.75–1.31, P = 0.94; HR versus RR: OR = 0.99, 95%CI = 0.90–1.09, P = 0.85). The results were not materially altered after the studies which did not fulfill Hardy-Weinberg equilibrium were excluded (H versus R: OR = 1.06, 95%CI = 0.95–1.19, P = 0.31; HR+HH versus RR: OR = 1.03, 95%CI = 0.93–1.13, P = 0.56; HH versus RR+HR: OR = 1.10, 95%CI = 0.78–1.56, P = 0.57; HH versus RR: OR = 1.09, 95%CI = 0.83–1.44, P = 0.53; HR versus RR: OR = 1.02, 95%CI = 0.92–1.13, P = 0.75).

Conclusion

This meta-analysis demonstrates that there is no association between the SULT1A1 R213H polymorphism and CRC.     

Associations between XPD Asp312Asn polymorphism and risk of head and neck cancer: a meta-analysis based on 7,122 subjects

Background

To investigate the association between XPD Asp312Asn polymorphism and head and neck cancer risk through this meta-analysis.

Methods

We performed a meta-analysis of 9 published case-control studies including 2,670 patients with head and neck cancer and 4,452 controls. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association between XPD Asp312Asn polymorphism and head and neck cancer risk.

Results

Overall, no significant association between XPD Asp312Asn polymorphism and head and neck cancer risk was found in this meta-analysis (Asn/Asn vs. Asp/Asp: OR = 0.95, 95%CI = 0.80–1.13, P = 0.550, P _{heterogeneity} = 0.126; Asp/Asn vs. Asp/Asp: OR = 1.11, 95%CI = 0.99–1.24, P = 0.065, P _{heterogeneity} = 0.663; Asn/Asn+Asp/Asn vs. Asp/Asp: OR = 1.07, 95%CI = 0.97–1.19, P = 0.189, P _{heterogeneity} = 0.627; Asn/Asn vs. Asp/Asp+Asp/Asn: OR = 0.87, 95%CI = 0.68–1.10, P = 0.243, P _{heterogeneity} = 0.089). In the subgroup analysis by HWE, ethnicity, and study design, there was still no significant association detected in all genetic models.

Conclusions

This meta-analysis demonstrates that XPD Asp312Asn polymorphism may not be a risk factor for developing head and neck cancer.     

The association between OGG1 Ser326Cys polymorphism and lung cancer susceptibility: a meta-analysis of 27 studies

Background

Numerous studies have investigated association of OGG1 Ser326Cys polymorphism with lung cancer susceptibility; however, the findings are inconsistent. Therefore, we performed a meta-analysis based on 27 publications encompass 9663 cases and 11348 controls to comprehensively evaluate such associations.

Methods

We searched publications from MEDLINE and EMBASE which were assessing the associations between OGG1 Ser326Cys polymorphism and lung cancer risk. We calculated pooled odds ratio (OR) and 95% confidence interval (CI) by using either fixed-effects or random-effects model. We used genotype based mRNA expression data from HapMap for SNP rs1052133 in normal cell lines among 270 subjects with four different ethnicities.

Results

The results showed that individuals carrying the Cys/Cys genotype did not have significantly increased risk for lung cancer (OR = 1.15, 95% CI = 0.98–1.36) when compared with the Ser/Ser genotype; similarly, no significant association was found in recessive, dominant or heterozygous co-dominant model (Ser/Cys vs. Cys/Cys). However, markedly increased risks were found in relatively large sample size (Ser/Ser vs. Cys/Cys: OR = 1.29, 95% CI = 1.13–1.48, and recessive model: OR = 1.19, 95% CI = 1.07–1.32). As to histological types, we found the Cys/Cys was associated with adenocarcinoma risk (Ser/Ser vs. Cys/Cys: OR = 1.32, 95% CI = 1.12–1.56; Ser/Cys vs. Cys/Cys: OR = 1.19, 95% CI = 1.04–1.37, and recessive model OR = 1.23, 95% CI = 1.08–1.40). No significant difference of OGG1 mRNA expression was found among genotypes between different ethnicities.

Conclusions

Despite some limitations, this meta-analysis established solid statistical evidence for an association between the OGG1 Cys/Cys genotype and lung cancer risk, particularly for studies with large sample size and adenocarcinoma, but this association warrants additional validation in larger and well designed studies.     

The effect of hOGG1 Ser326Cys polymorphism on cancer risk: evidence from a meta-analysis

Background

Human oxoguanine glycosylase 1 (hOGG1) in base excision repair (BER) pathway plays a vital role in DNA repair. Numerous epidemiological studies have evaluated the association between hOGG1 Ser326Cys polymorphism and the risk of cancer. However, the results of these studies on the association remain conflicting. To derive a more precise estimation of the association, we conducted a meta-analysis.

Methodology/Principal Findings

A comprehensive search was conducted to identify the eligible studies of hOGG1 Ser326Cys polymorphism and cancer risk. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. We found that the hOGG1 Ser326Cys polymorphism was significantly associated with overall cancer risk (Cys/Cys vs. Ser/Ser: OR = 1.19, 95%CI = 1.09–1.30, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.16, 95%CI = 1.08–1.26, P<0.001). Moreover, in subgroup analyses by cancer types, the stronger significant association between hOGG1 Ser326Cys polymorphism and lung cancer risk was found (Cys/Cys vs. Ser/Ser: OR = 1.29, 95%CI = 1.16–1.44, P<0.001; Cys/Cys vs. Cys/Ser+Ser/Ser: OR = 1.22, 95%CI = 1.12–1.33, P<0.001). The significant effects of hOGG1 Ser326Cys polymorphism on colorectal, breast, bladder, prostate, esophageal, and gastric cancer were not detected. In addition, in subgroup analyses by ethnicities, we found that the hOGG1 Ser326Cys polymorphism was associated with overall cancer risk in Asians (Cys/Cys vs. Ser/Ser: OR = 1.21, 95%CI = 1.10–1.33, P<0.001).

Conclusions

This meta-analysis showed that hOGG1 326Cys allele might be a low-penetrant risk factor for lung cancer.     

Hsa-miR-499 rs3746444 Polymorphism Contributes to Cancer Risk: A Meta-Analysis of 12 Studies

Background

Single nucleotide polymorphisms (SNPs) occurred in pre-microRNAs or targets of microRNAs (miRs) may contribute to cancer risks. Since 2007, many studies have investigated the association between common SNPs located on hsa-miR-499 (rs3746444) and cancer risks; however, the results were inconclusive.

Methodology/Principal Findings

We conducted a meta-analysis of 12 studies that included 5765 cases and 7076 controls to identify the strength of association. Odds ratio (OR) and 95% confidence intervals (95% CI) were used to assess the strength of association. Overall, individuals with the variant AG (OR = 1.215, 95% CI: 1.027, 1.437; P_{heterogeneity}<0.01) and AG/GG (OR = 1.227, 95% CI: 1.046, 1.439; P_{heterogeneity}<0.01) genotypes were associated with a significantly increased risk of cancer than those with wild AA genotype. Sub-group analysis revealed that the variant AG (OR = 1.411, 95% CI: 1.142, 1.745; P_{heterogeneity} = 0.01) and AG/GG (OR = 1.413, 95% CI: 1.163, 1.717, P_{heterogeneity} = 0.01) genotypes still showed an increased risk of cancer in Asians; however, a trend of reduced risk of cancer was observed in Caucasians (AG vs. AA: OR = 0.948, 955 CI: 0.851, 1.057, P_{heterogeneity} = 0.12; AG/GG vs. AA: OR = 0.959, 95% CI: 0.865, 1.064; P_{heterogeneity} = 0.19). Meta-regression showed that ethnicity (p = 0.048) and sample size (p = 0.02) but not cancer types (p = 0.89) or source of control (p = 0.97) were the sources of heterogeneity.

Conclusions

These meta-analysis results suggest that hsa-miR-499 polymorphism rs3746444 is associated with a significantly increased risk of cancer, especially in Asian populations.     

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.     

A genetic variant in the promoter region of miR-106b-25 cluster and risk of HBV infection and hepatocellular carcinoma

Background

MiR-106b-25 cluster, hosted in intron 13 of MCM7, may play integral roles in diverse processes including immune response and tumorigenesis. A single nucleotide polymorphism (SNP), rs999885, is located in the promoter region of MCM7.

Methods

We performed a case-control study including 1300 HBV-positive hepatocellular carcinoma (HCC) cases, 1344 HBV persistent carriers and 1344 subjects with HBV natural clearance to test the association between rs999885 and the risk of HBV persistent infection and HCC. We also investigated the genotype-expression correlation between rs999885 and miR-106b-25 cluster in 25 pairs of HCC and adjacent non-tumor liver tissues.

Results

Compared with the HBV natural clearance subjects carrying rs999885 AA genotype, those with AG/GG genotypes had a decreased risk of chronic HBV infection with an adjusted odds ratio (OR) of 0.79 [95% confidence intervals (CIs) = 0.67–0.93]. However, the AG/GG genotypes were significantly associated with an increased HCC risk in HBV persistent carriers (adjusted OR = 1.25, 95% CIs = 1.06–1.47). Expression analysis revealed that the expression level of miR-106b-25 cluster was significantly higher in AG/GG carriers than those in AA carriers in non-tumor liver tissues.

Conclusions

These findings indicate that the A to G base change of rs999885 may provide a protective effect against chronic HBV infection but an increased risk for HCC in HBV persistent carriers by altering the expression of the miR-106b-25 cluster.     

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 study of the β2-adrenergic receptor gene polymorphisms and hypertension in the Northern Han Chinese

Background

The β2-adrenergic receptor (ADRB2) gene has been widely researched as a candidate gene for essential hypertension (EH), but no consensus has been reached in different ethnicities. The aim of the present study was to evaluate the possible association between the ADRB2 gene polymorphisms and the EH risk in the Northern Han Chinese population.

Methodology/Principal Findings

This study included 747 hypertensive subjects and 390 healthy volunteers as control subjects in the Northern Han Chinese. Genotyping was performed to identify the C-47T, A46G and C79G polymorphisms of the ADRB2 gene. G allelic frequency of A46G polymorphism was significantly higher in hypertensive subjects (P = 0.011, OR = 1.287, 95%CI [1.059–1.565]) than that in controls. Significant association could also be found in dominant genetic model (GG+AG vs. AA, P = 0.006, OR = 1.497, 95%CI [1.121–1.998]), in homozygote comparison (GG vs. AA, P = 0.025, OR = 1.568, 95%CI [1.059–2.322]), and in additive genetic model (GG vs. AG vs. AA, P = 0.012, OR = 1.282, 95%CI [1.056–1.555]). Subgroup analyses performed by gender suggested that this association could be found in male, but not in female. Stratification analyses by obesity showed that A46G polymorphism was related to the prevalence of hypertension in the obese population (GG vs. AG vs. AA, P<0.001, OR = 1.645, 95%CI [1.258–2.151]). Significant interaction was found between A46G genotypes and body mass index on EH risk. No significant association could be found between C-47T or C79G polymorphism and EH risk. Linkage disequilibrium was detected between the C-47T, A46G and C79G polymorphisms. Haplotype analyses observed that the T-47-A46-C79 haplotype was a protective haplotype for EH, while the T-47-G46-C79 haplotype increased the risk.

Conclusions/Significances

We revealed that the ADRB2 A46G polymorphism might increase the risk for EH in the Northern Han Chinese population.     

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.     

Polymorphisms on 8q24 are associated with lung cancer risk and survival in han chinese

Chromosome 8q24 is commonly amplified in many types of cancer, particularly lung cancer. Polymorphisms in this region are associated with risk of different cancers. To investigate the relationship between three single nucleotide polymorphisms (SNPs) (rs1447295, rs16901979 and rs6983267) on 8q24 and lung cancer risk, we conducted an association study in two Han Chinese populations: one population was from Zhejiang Province (576 case patients and 576 control subjects), whereas the other was from Fujian Province (576 case patients and 576 control subjects). We found that rs6983267 was significantly associated with an increased risk of lung cancer in both populations. Compared with the TT genotype, the GG genotype was associated with a significant 1.555-fold increased risk of lung cancer [95% confidence interval (CI) 1.218–1.986, P = 4.0×10⁻⁴]. This effect was more pronounced in never-smokers [odds ratio (OR) = 2.366, 95% CI 1.605–3.488, P = 1.4×10⁻⁵]. Analyses stratified by histology revealed that rs6983267 GG genotype was most associated with patients with other histological types (OR = 3.012, 95% CI 1.675–5.417, P = 2.3×10⁻⁴). The AA genotype of rs1447295 was associated with increased risk for adenocarcinoma compared with the CC genotype (OR = 2.260, 95% CI 1.174–4.353, P = 0.015). Furthermore, the GG genotype of rs6983267 was associated with worse survival in the Zhejiang population (hazard ratio (HR) = 1.646, 95% CI 1.099–2.464, P = 0.016). No association was observed for rs16901979. These results suggest that genetic variations on 8q24 may play significant roles in the development and progression of lung cancer.