The SNP rs402710 in 5p15.33 Is Associated with Lung Cancer Risk: A Replication Study in Chinese Population and a Meta-Analysis

Background

Lung cancer is the most commonly diagnosed cancer and leading cause of cancer mortality in the world. A single nucleotide polymorphism (SNP), rs402710, located in 5p15.33, was firstly identified to be associated with the lung cancer risk in a genome-wide association study. However, some following replication studies yielded inconsistent results.

Methodology and Findings

A case-control study of 611 cases and 1062 controls in a Chinese population was conducted, and then a meta-analysis integrating the current and previously published studies with a total 31811 cases and 36333 controls was performed to explore the real effect of rs402710 on lung cancer susceptibility. Significant associations between the SNP rs402710 and lung cancer risk were observed in both case-control study and meta-analysis, with ORs equal to 0.77 (95%CI = 0.63–0.95) and 0.83 (95%CI = 0.81–0.86) in dominant model, respectively. By stratified analysis of our case-control study, the associations were also observed in never smoker group and non-small cell lung cancer(NSCLC) group with ORs equal to 0.71 (95%CI = 0.53–0.95) and 0.69 (95%CI = 0.55–0.87), which was remarkable that larger effect of the minor allele T was seen in the two groups than that in overall lung cancer. Besides, the sensitive and cumulative analysis indicated the robust stability of the current results of meta-analysis.

Conclusion

The results from our replication study and the meta-analysis provided firm evidence that rs402710 T allele significantly contributed to decreased lung cancer risk, and the case-control study implied that the variant may yield stronger effect on NSCLC and never smokers. However, the mechanism underlying the polymorphism conferring susceptibility to lung cancer is warranted to clarify in the follow-up studies.     

Systematic Review and Meta-Analysis of the Relationship between EPHX1 Polymorphisms and Colorectal Cancer Risk

Background

Microsomal epoxide hydrolase (EPHX1) plays an important role in both the activation and detoxification of PAHs, which are carcinogens found in cooked meat and tobacco smoking. Polymorphisms at exons 3 and 4 of the EPHX1 gene have been reported to be associated with variations in EPHX1 activity. The aim of this study is to quantitatively summarize the relationship between EPHX1 polymorphisms and colorectal cancer (CRC) risk.

Methods

Two investigators independently searched the Medline, Embase, CNKI, and Chinese Biomedicine Databases for studies published before June 2012. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for EPHX1 Tyr113His (rs1051740) and His139Arg (rs2234922) polymorphisms and CRC were calculated in a fixed-effects model and a random-effects model when appropriate.

Results

This meta-analysis yielded 14 case-control studies, which included 13 studies for Tyr113His (6395 cases and 7893 controls) and 13 studies for His139Arg polymorphisms (5375 cases and 6962 controls). Overall, the pooled results indicated that EPHX1 Tyr113His polymorphism was not associated with CRC risk; while the His139Arg polymorphism was significantly associated with decreased CRC risk (Arg/His vs. His/His, OR = 0.90, 95%CI = 0.83–0.98; dominant model, OR = 0.92, 95%CI = 0.85–0.99). The statistically significant association between EPHX1 His139Arg polymorphism and CRC was observed among Caucasians and population-based case-control studies. This association showed little heterogeneity and remained consistently strong when analyses were limited to studies in which genotype frequencies were in Hardy–Weinberg equilibrium, or limited to studies with matched controls. When cumulative meta-analyses of the two associations were conducted by studies’ publication time, the results were persistent and robust.

Conclusion

This meta-analysis suggests that EPHX1 Tyr113His polymorphism may be not associated with CRC development; while the EPHX1 His139Arg polymorphism may have a potential protective effect on CRC.     

A Genetic Variant rs1801274 in FCGR2A as a Potential Risk Marker for Kawasaki Disease: A Case-Control Study and Meta-Analysis

Objectives

Recent genome-wide association study found rs1801274, a functional single nucleotide polymorphism (SNP) in IgG receptor gene FCGR2A, was associated with increased risk of Kawasaki disease (KD). However, subsequent studies on the role of this SNP were limited and controversial.

Methods

A case-control study was conducted in a Chinese Han population including 428 KD patients and 493 controls to examine the association between rs1801274 and KD susceptibility. A meta-analysis was performed in combination with the relevant published studies to further clarify such an association.

Results

Our case-control study found that rs1801274 was significantly associated with increased risk of KD in the Chinese Han population, with an odds ratio (OR) of 1.58 (95% CI = 0.96–2.62) for the GA genotype and 1.93 (95% CI = 1.16–3.19) for the AA genotype compared with the GG genotype. The result of meta-analysis further demonstrated that the A allele of rs1801274 was significantly correlated with KD risk under the allelic model (OR = 1.35, 95% CI = 1.27–1.44) without heterogeneity by fixed-effects model analysis (Q = 17.30, p = 0.139). Moreover, sensitivity analysis supported the robustness of this meta-analysis.

Conclusion

These results further confirm that rs1801274 in the FCGR2A gene is significantly associated with increased risk of KD.     

A common SMAD7 variant is associated with risk of colorectal cancer: evidence from a case-control study and a meta-analysis

Background

A common genetic variant, rs4939827, located in SMAD7, was identified by two recent genome-wide association (GWA) studies to be strongly associated with the risk of colorectal cancer (CRC). However, the following replication studies yielded conflicting results.

Method and Findings

We conducted a case-control study of 641 cases and 1037 controls in a Chinese population and then performed a meta-analysis, integrating our and published data of 34313 cases and 33251 controls, to clarify the relationship between rs4939827 and CRC risk. In our case-control study, the dominant model was significant associated with increased CRC risk [Odds Ratio (OR) = 1.46; 95% confidence interval (95% CI), 1.19–1.80]. The following meta-analysis further confirmed this significant association for all genetic models but with significant between-study heterogeneity (all P for heterogeneity <0.1). By stratified analysis, we revealed that ethnicity, sample size, and tumor sites might constitute the source of heterogeneity. The cumulative analysis suggested that evident tendency to significant association was seen with adding study samples over time; whilst, sensitive analysis showed results before and after removal of each study were similar, indicating the highly stability of the current results.

Conclusion

Results from our case-control study and the meta-analysis collectively confirmed the significant association of the variant rs4939827 with increased risk of colorectal cancer. Nevertheless, fine-mapping of the susceptibility loci defined by rs4939287 should be imposed to reveal causal variant.     

Lack of Association between NADPH Quinone Oxidoreductase 1 (NQO1) Gene C609T Polymorphism and Lung Cancer: A Case-Control Study and a Meta-Analysis

Background

The association between NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism (rs1800566) and lung cancer has been widely evaluated, and a definitive answer so far is lacking. We first conducted a case-control study to assess this association in northeastern Han Chinese, and then performed a meta-analysis to further address this issue.

Methodology/Principal Findings

This case-control study involved 684 patients clinically diagnosed as lung cancer and 602 age-matched cancer-free controls from Harbin city, Heilongjiang province, China. Genotyping was conducted using the PCR-LDR (ligase detection reactions) method. Meta-analysis was managed by STATA software. Data and study quality were assessed in duplicate. Our case-control association study indicated no significant difference in the genotype and allele distributions of C609T polymorphism between lung cancer patients and controls, consistent with the results of the further meta-analysis involving 7286 patients and 9167 controls under both allelic (odds ratio (OR) = 0.99; 95% confidence interval (CI): 0.92–1.06; P = 0.692) and dominant (OR = 0.98; 95% CI: 0.89–1.08; P = 0.637) models. However, there was moderate evidence of between-study heterogeneity and low probability of publication bias. Further subgroup analyses by ethnicity, source of controls and sample size detected no positive associations in this meta-analysis.

Conclusions

Our study in northeastern Han Chinese, along with the meta-analysis, failed to confirm the association of NQO1 gene C609T polymorphism with lung cancer risk, even across different ethnic populations.     

The SNP rs961253 in 20p12.3 is associated with colorectal cancer risk: a case-control study and a meta-analysis of the published literature

Background

Colorectal cancer (CRC) is the third common cancer and the fourth leading cause of cancer death worldwide. A single nucleotide polymorphism (SNP), rs961253 located in 20p12, was firstly described to be associated with the increased risk of CRC in a genome-wide association study; however, more recent replication studies yielded controversial results.

Methodology/Principal Findings

A hospital-based case-control study in a Chinese population was firstly performed, and then a meta-analysis combining the current and previously published studies were conducted to explore the real effect of rs961253 in CRC susceptibility. In the Chinese population including 641 cases and 1037 controls, per-A-allele conferred an OR of 1.60 (95% CI = 1.26–2.02) under additive model. In the meta-analysis including 29859 cases and 29696 controls, per-A-allele have an OR of 1.13 (95% CI = 1.09–1.18) under a random-effects model due to heterogeneity (P = 0.019). Nevertheless, the heterogeneity can be totally explained by ethnicity, with the tau²reduced to 0 after including ethnicity in meta-regression model. In stratified analysis by ethnicity, per-A-allele had ORs of 1.34 (95% CI = 1.20–1.50) and 1.11 (95% CI = 1.08–1.14) for Asian and European, respectively, without heterogeneity. Modest influence of each study was observed on overall estimate in sensitive analysis, and evident tendency to significant association was seen in cumulative analysis over time, together indicating the robust stability of the current results.

Conclusions/Significance

The results from our study and the meta-analysis provided firm evidence that rs961253 significantly contributed to CRC risk in both Asian and European population.     

A Common Polymorphism near the ESR1 Gene Is Associated with Risk of Breast Cancer: Evidence from a Case-Control Study and a Meta-Analysis

Background

Genome-wide association studies have reported that a polymorphism near the estrogen receptor gene (ESR1) (rs2046210) is associated with a risk of breast cancer, with the A allele conferring an increased risk. However, considering the controversial results from more recent replicated studies, we conducted a case-control study in an independent Chinese Han population and a meta-analysis to clarify the association of this polymorphism with breast cancer risk.

Method and Findings

A hospital-based case-control study including 461 cases and 537 controls from a Chinese Han population was conducted initially, and this study showed that the rs2046210 A allele was significantly associated with breast cancer risk, with an OR of 1.32 (95% CI  = 1.10–1.59). Subsequently, a meta-analysis integrating the current study and previous publications with a total of 53,379 cases and 55,493 controls was performed to further confirm our findings. Similarly, a significant association between this polymorphism and breast cancer risk was also observed in the overall population especially among Asians, with ORs for per A allele of 1.14 (95% CI  = 1.10–1.18) in the overall population and 1.27 (95% CI  = 1.23–1.31) in the Asian population.

Conclusion

Our results provide strong evidence to support that the common polymorphism near the ESR1 gene, rs2046210, is associated with an increased risk of breast cancer in Asian and European populations but not in Africans, although the biological mechanisms need to be further investigated.     

Association of SMAD7 rs12953717 Polymorphism with Cancer: A Meta-Analysis

Background

Accumulating evidence has suggested that Mothers against decapentaplegic homolog 7 (SMAD7) rs12953717 polymorphism might be related to cancer risk. However, epidemiologic findings have been inconsistent. We therefore performed a meta-analysis to clarify the association between the SMAD7 rs12953717 polymorphism and cancer risk.

Methods

A comprehensive search was conducted to identify all eligible studies of SMAD7 rs12953717 polymorphism and cancer risk. We used odds ratios (ORs) to assess the strength of the association, and 95% confidence intervals (CIs) to give a sense of the precision of the estimate. Heterogeneity, publication bias, and sensitivity analysis were also explored.

Results

A total of 14 case-control studies, including 16928 cases and 14781 controls, were included in the present meta-analysis. The overall results showed that the variant genotypes were associated with a significantly increased risk of all cancer types (homozygote comparison, OR = 1.23, 95%CI = 1.10–1.38, P<0.01; heterozygote comparison, OR = 1.12, 95%CI = 1.02–1.22, P = 0.02; recessive model, OR = 1.17, 95%CI = 1.07–1.29, P<0.01; dominant model, OR = 1.15, 95%CI = 1.06–1.25, P<0.01; allelic model, OR = 1.12, 95%CI = 1.06–1.18, P<0.01). Further sensitivity analysis confirmed the significant association. In the subgroup analysis by ethnicity, SMAD7 rs12953717 polymorphism was significantly associated with cancer risk in both Caucasians and Asians. In the subgroup analysis by cancer types, SMAD7 rs12953717 polymorphism was significantly associated with colorectal cancer.

Conclusions

Our investigations demonstrate that rs12953717 polymorphism is associated with the susceptibility of cancer. Large-scale and well-designed case-control studies are necessary to validate the risk identified in the present meta-analysis.     

Population Specific Impact of Genetic Variants in KCNJ11 Gene to Type 2 Diabetes: A Case-Control and Meta-Analysis Study

Background and Objectives

Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis.

Methods

A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochran''s Q, I² statistics were used to study heterogeneity between the eligible studies.

Results

KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83–1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians.

Conclusion

KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.     

Age at Menarche and Risk of Colorectal Cancer: A Meta-Analysis

Background

Various observational studies have focused on the relationship between menarcheal age and the risk of colorectal cancer (CRC). However, the association is still controversial because of inconsistent results. Therefore, we performed a meta-analysis to assess this issue from epidemiological studies.

Methods

After a literature search in MEDLINE, EMBASE, and Web of Science for studies of menarcheal age and CRC risk published through the end of January 2013, we pooled the relative risks (RRs) from included studies using a fixed- or random-effects model and performed heterogeneity and publication bias analyses. All statistical tests were two-sided.

Results

Eleven case-control and 11 cohort studies were eligible for inclusion in our analysis. The random-effects pooled RR for oldest versus youngest menarcheal age was 0.95 [95% confidence intervals (CIs) = 0.85–1.06], with significant heterogeneity (Q = 61.03, P<0.001, I ² = 65.6%). When separately analyzed, case-control (RR = 0.95, 95% CI = 0.75–1.21) and cohort studies (RR = 0.97, 95% CI = 0.90–1.04) yielded similar results. Moreover, similar results were also observed among the subgroup analyses by study quality, population, exposure assessment, anatomic cancer site, subsite of colon cancer, and several potential important confounders and risk factors. There was no evidence of publication bias and significant heterogeneity between subgroups detected by meta-regression analyses.

Conclusions

Findings from this meta-analysis demonstrated that menarcheal age was not associated with the risk of CRC in humans. Further studies are warranted to stratify results by the subsite of colon cancer and menopause status in the future.     

Replication Study in Chinese Population and Meta-Analysis Supports Association of the 5p15.33 Locus with Lung Cancer

Background

Common genetic polymorphisms on chromosome 5p15.33, including rs401681 in cleft lip and palate transmembrane 1-like gene (CLPTM1L), have been implicated in susceptibility to lung cancer through genome-wide association studies (GWAS); however, subsequent replication studies yielded controversial results.

Methodology and Findings

A hospital-based case-control study in a Chinese population was conducted to replicate the association, and then a meta-analysis combining our non-overlapping new data and previously published data was performed to clearly discern the real effect of lung cancer susceptibility. In our study with 611 cases and 1062 controls, the minor allele T carrier (TT plus CT) group conferred an OR of 0.801 (95% CI = 0.654–0.981) under the dominant model. The meta-analysis comprising 9111 cases and 11424 controls further confirmed the significant association in the dominant model (OR = 0.842, 95% CI = 0.795–0.891). By stratified analysis, we revealed that ethnicity and study design might constitute the source of between-study heterogeneity. Besides, the sensitivity and cumulative analyses indicated the high stability of the results.

Conclusion

The results from our case-control study and meta-analysis provide convincing evidence that rs401681 is significantly associated with lung cancer risk.     

Association between Extremely Low-Frequency Electromagnetic Fields Occupations and Amyotrophic Lateral Sclerosis: A Meta-Analysis

Objectives

To estimate the relationship between exposure to extremely low-frequency electromagnetic fields (ELF-EMF) and the risk of amyotrophic lateral sclerosis (ALS) by a meta-analysis.

Methods

Through searching PubMed databases (or manual searching) up to April 2012 using the following keywords: “occupational exposure”, “electromagnetic fields” and “amyotrophic lateral sclerosis” or “motor neuron disease”, seventeen studies were identified as eligible for this meta-analysis. The associations between ELF-EMF exposure and the ALS risk were estimated based on study design (case-control or cohort study), and ELF-EMF exposure level assessment (job title or job-exposure matrix). The heterogeneity across the studies was tested, as was publication bias.

Results

Occupational exposure to ELF-EMF was significantly associated with increased risk of ALS in pooled studies (RR = 1.29, 95%CI = 1.02–1.62), and case-control studies (OR = 1.39, 95%CI = 1.05–1.84), but not cohort studies (RR = 1.16, 95% CI = 0.80–1.69). In sub-analyses, similar significant associations were found when the exposure level was defined by the job title, but not the job-exposure matrix. In addition, significant associations between occupational exposure to ELF-EMF and increased risk of ALS were found in studies of subjects who were clinically diagnosed but not those based on the death certificate. Moderate heterogeneity was observed in all analyses.

Conclusions

Our data suggest a slight but significant ALS risk increase among those with job titles related to relatively high levels of ELF-EMF exposure. Since the magnitude of estimated RR was relatively small, we cannot deny the possibility of potential biases at work. Electrical shocks or other unidentified variables associated with electrical occupations, rather than magnetic-field exposure, may be responsible for the observed associations with ALS.     

KCNE1 rs1805127 Polymorphism Increases the Risk of Atrial Fibrillation: A Meta-Analysis of 10 Studies

Background

Atrial fibrillation (AF) is one of the most common types of arrhythmia in humans. Recently, many studies have investigated the relationship between human atrial fibrillation and the single nucleotide polymorphism (SNP) of rs1805127 (A>G) in KCNE1 gene, but the results were still inconsistent and inconclusive.

Method

Electronic databases and bibliographies of retrieved studies were searched. We performed a meta-analysis of ten case-control studies, including 2099 cases and 2252 controls, to evaluate the association of rs1805127 polymorphism (A>G) with the risk of AF. Random-effects model was used when the heterogeneity was obvious; otherwise, fixed-effects model was applied. Meta-regression was performed to examine potential source of heterogeneity. Egger''s test and Begg''s test were used to detect publication biases.

Results

The results showed a significantly increased risk of AF in homozygote comparison (GG vs. AA:OR = 1.899, 95%CI: 1.568, 2.300; P_{heterogeneity} = 0.217), heterozygote comparison (GA vs. AA:OR = 1.436, 95% CI:1.190, 1.732; P_{heterogeneity} = 0.739), dominant model(GA /GG vs. AA: OR = 1.624, 95%CI: 1.361, 1.938; P_{heterogeneity} = 0.778) and recessive model (GG vs. GA/AA: OR = 1.394, 95%CI:1.152, 1.686; P_{heterogeneity} = 0.03). Meta-regression revealed that the sample size and the types of AF were the source of the heterogeneity.

Conclusion

The rs1805127 polymorphism (A>G) of KCNE1 is associated with an increased risk of AF, which suggests the rs1805217 polymorphism of KCNE1 gene may play an important role in the pathogenesis of AF.     

Association between Polymorphism of the Vitamin D Metabolism Gene CYP27B1 and HLA-B27-Associated Uveitis. Is a State of Relative Immunodeficiency Pathogenic in HLA B27-Positive Uveitis?

Objective

Polymorphisms of the vitamin D metabolism gene CYP27B1 showed associations with multiple autoimmune diseases. The aim of this study was to investigate a possible association between the rs703842 A>G polymorphism of the CYP27B1 gene and HLA-B27-associated uveitis.

Design

One hundred fifty-nine patients with HLA-B27-associated uveitis, 138 HLA-B27-negative controls and 100 HLA-B27-positive controls were recruited for this retrospective case-control study. Main outcome parameters were genotype distribution and allelic frequencies determined by polymerase chain reaction.

Results

Carriers of the rs703842G allele were found significantly more often in patients with HLA-B27-associated uveitis than in HLA-B27-positive controls (p = 0.03). Between patients and HLA-B27-negative controls no significant difference in the genotype distribution of the rs703842 A>G polymorphism was found (p = 0.97).

Conclusions

Our data suggest that the rs703842 A>G polymorphism may play a role in HLA-B27-associated uveitis.     

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 Meta-Analysis of the Association between the hOGG1 Ser326Cys Polymorphism and the Risk of Esophageal Squamous Cell Carcinoma

Background

Genetic polymorphism of human 8-oxoguanine glycosylase 1 (hOGG1) Ser326Cys (rs1052133) has been implicated in the risk of Esophageal Squamous Cell Carcinoma (ESCC). However, the published findings are inconsistent. We therefore performed a meta-analysis to derive a more precise estimation of the association between the hOGG1 Ser326Cys polymorphism and ESCC risk.

Methodology/Principal Findings

A comprehensive search was conducted to identify eligible studies of hOGG1 Ser326Cys polymorphism and the risk of the ESCC. Three English and two Chinese databases were used, and ten published case-control studies, including 1987 cases and 2926 controls were identified. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the association in the dominant and recessive model. Pearson correlation coefficient (PCC) and standard error (SE) were used to assess the number of Cys allele and ESCC risk in the additive model. Overall, significant associations between the hOGG1 Ser326Cys polymorphism and ESCC risk were found in the recessive model: OR = 1.37 (95% CI: 1.06–1.76, p = 0.02). We also observed significant associations in the Caucasian, Chinese language, population based control and tissue subgroups. In the additive model, positive correlation was found between the number of Cys allele and the risk of ESCC in overall studies (PCC = 0.109, SE = 0.046, p = 0.02), Caucasian subgroup and population subgroup. Funnel plot and Egger''s test indicate there was no publication bias in this meta-analysis.

Conclusion

Under the published data, the hOGG1 Ser326Cys polymorphism is associated with ESCC risk in the recessive and additive model. Compared with the Ser/Ser and Ser/Cys genotype, Cys/Cys genotype might contribute to increased risk of ESCC. And the risk of ESCC is positively correlated with the number of Cys allele. A better case-control matched study should be designed in order to provide a more precise estimation.     

Association between MLH1 -93G>A Polymorphism and Risk of Colorectal Cancer

Background

The -93G>A (rs1800734) polymorphism located in the promoter of mismatch repair gene, MLH1, has been identified as a low-penetrance variant for cancer risk. Many published studies have evaluated the association between the MLH1 -93G>A polymorphism and colorectal cancer (CRC) risk. However, the results remain conflicting rather than conclusive.

Objective

The aim of this study was to assess the association between the MLH1 -93G>A polymorphism and the risk of CRC.

Methods

To derive a more precise estimation of the association, a meta-analysis of six studies (17,791 cases and 13,782 controls) was performed. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the association. Four of these published studies were performed on subjects of known microsatellite instability (MSI) status. An additional analysis including 742 cases and 10,895 controls was used to assess the association between the MLH1 -93G>A polymorphism and the risk of MSI-CRC.

Results

The overall results indicated that the variant genotypes were associated with a significantly increased risk of CRC (AG versus GG: OR = 1.06, 95% CI = 1.01–1.11; AA/AG versus GG: OR = 1.06, 95% CI = 1.01–1.11). This increased risk was also found during stratified analysis of MSI status (AA versus GG: OR = 2.52, 95% CI = 1.94–3.28; AG versus GG: OR = 1.29, 95% CI = 1.10–1.52; AA/AG versus GG: OR = 1.45, 95% CI = 1.24–1.68; AA versus AG/GG: OR = 2.29, 95% CI = 1.78–2.96). Egger’s test did not show any evidence of publication bias.

Conclusion

Our results suggest that the MLH1 -93G>A polymorphism may contribute to individual susceptibility to CRC and act as a risk factor for MSI-CRC.     

Association of the Ephreceptor Tyrosinekinase-Type A2 (EPHA2) Gene Polymorphism rs3754334 with Age-Related Cataract Risk: A Meta-Analysis

Background

Recent clinical studies have assessed the association of various polymorphisms on the ephreceptor tyrosinekinase-type A2 (EPHA2) with the risk for age-related cataract in populations of different ethnic/racial backgrounds, but inconsistent results have been obtained.

Objective

This meta-analysis aimed to identify if any polymorphism(s) might be commonly present in different ethnic/racial populations in association with the age-related cataract risk.

Methods

The PubMed and Web of Science databases (up to December 1, 2012) were searched for clinical studies on the association of EPHA2 polymorphisms with the risk for age-related cataract. The polymorphisms that were assessed in all eligible studies were analyzed for their association with the risk for age-related cataract using different models.

Results

Three studies were identified, which were conducted, respectively, on white Americans in the Unites States and on Asians in Indian and China. The polymorphism, rs3754334, was the only one studied in all these three studies and was therefore the focus of this meta-analysis. No publication bias or heterogeneity was found. Our analysis results demonstrated that rs3754334 was associated with the risk of any cataracts in the recessive (OR = 1.202, 95% CI: 1.051–1.375, P = 0.007) and Codominant (OR = 1.194, 95% CI: 1.035–1.378, P = 0.015) models, but its association with cortical or nuclear phenotype of age-related cataract was not evident.

Conclusion

Polymorphism, rs3754334, might be a variant on the EPHA2 gene that is commonly associated with the risk for age-related cataract in different ethnical and geographical populations.     

Vascular Endothelial Growth Factor +936C/T, –634G/C, –2578C/A,and –1154G/A Polymorphisms with Risk of Preeclampsia: A Meta-Analysis

Background

Emerging evidence showed that VEGF gene polymorphisms are involved in the regulation of VEGF protein expression, thus increasing an individual''s susceptibility to preeclampsia (PE); but individually published results are inconclusive. The aim of this meta-analysis was to investigate the associations between VEGF gene polymorphisms and PE risk.

Methods

A systematic literature search of MEDLINE, Embase, Web of Science, and CNKI (Chinese National Knowledge Infrastructure) databases was conducted. Statistical analyses were performed using STATA 12.0 software and Review manager 5.1. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

According to the inclusion criteria, 11 case-control studies were finally included in this meta-analysis. A total of 1,069 PE cases and 1,315 controls were included in this study. Our meta-analysis indicated that VEGF +936C/T (T vs. C, OR = 1.52, 95%CI = 1.08–2.12) or −634G/C polymorphism (C vs. G, OR = 1.24, 95% CI = 1.03–1.50) was associated with the risk of PE, whereas there was no association between −2578C/A (A vs. C, OR = 0.98, 95%CI = 0.82–1.16) or −1154G/A (A vs. G, OR = 1.30, 95%CI = 0.94–1.78) polymorphism and PE risk in our study.

Conclusion

Our meta-analysis suggested that VEGF −2578C/A or −1154G/A polymorphism had no association with PE risk in all examined patients, whereas there was an association between VEGF +936C/T or −634G/C polymorphism and risk of PE.     

Comprehensive Review of Genetic Association Studies and Meta-Analyses on miRNA Polymorphisms and Cancer Risk

Background

MicroRNAs (miRNAs) are small RNA molecules that regulate the expression of corresponding messenger RNAs (mRNAs). Variations in the level of expression of distinct miRNAs have been observed in the genesis, progression and prognosis of multiple human malignancies. The present study was aimed to investigate the association between four highly studied miRNA polymorphisms (mir-146a rs2910164, mir-196a2 rs11614913, mir-149 rs2292832 and mir-499 rs3746444) and cancer risk by using a two-sided meta-analytic approach.

Methods

An updated meta-analysis based on 53 independent case-control studies consisting of 27573 cancer cases and 34791 controls was performed. Odds ratio (OR) and 95% confidence interval (95% CI) were used to investigate the strength of the association.

Results

Overall, the pooled analysis showed that mir-196a2 rs11614913 was associated with a decreased cancer risk (OR = 0.846, P = 0.004, TT vs. CC) while other miRNA SNPs showed no association with overall cancer risk. Subgroup analyses based on type of cancer and ethnicity were also performed, and results indicated that there was a strong association between miR-146a rs2910164 and overall cancer risk in Caucasian population under recessive model (OR = 1.274, 95%CI = 1.096–1.481, P = 0.002). Stratified analysis by cancer type also associated mir-196a2 rs11614913 with lung and colorectal cancer at allelic and genotypic level.

Conclusions

The present meta-analysis suggests an important role of mir-196a2 rs11614913 polymorphism with overall cancer risk especially in Asian population. Further studies with large sample size are needed to evaluate and confirm this association.