Case-free Controls Research Articles

Effects of three common polymorphisms in microRNAs on lung cancer risk: a meta-analysis

Background: Many studies demonstrated that miRNAs could affect the initiation and progression of malignant tumor. Recently, many studies on the association of these three common polymorphisms ( miR-146a, miR-196a2 and miR-499 ) with lung cancer risk found inconsistent results. Methods: These studies were collected from PubMed, Wanfang, VIP and CNKI database. ORs (odds ratios) with 95% CIs (confidence intervals) were used to assess the association between three genetic polymorphisms and the risk of lung cancer. All results were performed by using the Stata 14 software. Results: Eleven studies including 9,231 lung cancer cases and 9,280 case-free controls were analyzed in this meta-analysis. The analysis revealed that a significant association was found between miR-146a polymorphism and lung cancer (CG vs . CC, GG vs . CC, GG + CG vs . CC, G vs . C: OR =0.859, 95% CI: 0.781–0.945, P=0.002; OR =0.846, 95% CI: 0.751–0.953, P=0.006; OR =0.855, 95% CI: 0.782–0.935, P=0.001; OR= 0.910, 95% CI: 0.859–0.964, P=0.001, respectively). We also found that the significant association between miR-146a polymorphism and the risk of lung cancer was found among hospital-based population. We found that miR-196a2 polymorphism was associated with an increased lung cancer risk (CC vs . TT: OR =1.200, 95% CI: 1.056–1.364, P=0.005; CC + CT vs . TT: OR =1.117, 95% CI: 1.011–1.235, P=0.029; CC vs . CT + TT: OR =1.123, 95% CI: 1.009–1.251, P=0.034; C vs . T: OR =1.089, 95% CI: 1.022–1.161, P=0.008, respectively). For the Asian samples alone, we achieved the same results. Subgroup analysis found that a statistically association between miR-196a2 (rs11614913) and the lung cancer risk among hospital-based. There was significant association between miR-499 and lung cancer (AG vs . AA: OR =1.131, 95% CI: 1.022–1.252, P=0.018; GG vs . AA: OR =1.702, 95% CI: 1.093–2.650, P=0.019; AG + GG vs . AA: OR =1.207, 95% CI: 1.042–1.398, P=0.012; GG vs . AG + AA: OR =1.640, 95% CI: 1.066–2.523, P=0.024; G vs . A: OR =1.226, 95% CI: 1.026–1.464, P=0.025, respectively). Conclusions: All three common polymorphisms in microRNA are associated with the risk of lung cancer.

No association between the progesterone receptor gene polymorphism (+331G/a) and the risk of breast cancer: an updated meta-analysis

BackgroundMany published studies have estimated the association between the +331G/A (rs10895068) polymorphism in the progesterone receptor (PgR) gene and breast cancer risk. However, the results remain inconsistent and controversial. To address this inconsistency, we systematically interrogated the aforementioned association via a meta-analysis.MethodsThrough a literature search, we identified 13 case-control studies, including 12,453 cases and 14,056 case-free controls. The strengths of reported associations were evaluated using odds ratios (ORs) with 95% confidence intervals (95%CIs).ResultsAn association was found between +331G/A polymorphism and +331G/A risk in the dominant model (p = 0.027). Via subgroup analysis, we found no association between +331G/A and breast cancer risk in Caucasians, Asians or mixed racial groups.ConclusionsThrough meta-analysis, we were able to gain insight into previously reported associations between +331G/A polymorphism and breast cancer risk. However, further studies are still needed to provide more evidence.

Association between MTHFR C677T polymorphism and abdominal aortic aneurysm risk: A comprehensive meta-analysis with 10,123 participants involved.

Background:Abdominal aortic aneurysm (AAA) is a life-threatening condition. A number of studies reported the association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and AAA risk, but substantial controversial findings were observed and the strength of the association remains unclear.Objective:The aim of this study was to investigate the aforementioned association in the overall population and different subgroups.Methods:PUBMED and EMBASE databases were searched until March 2016 to identify eligible studies, restricted to humans and articles published in English. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to AAA. Subgroup meta-analyses were conducted on features of the population, such as ethnicity, sex of the participants, and study design (source of control).Results:Twelve case–control studies on MTHFR C677T polymorphism and AAA risk, including 3555 cases and 6568 case-free controls were identified. The results revealed no significant association between the MTHFR C677T polymorphism and AAA risk in the overall population and within Caucasian or Asian subpopulations in all 5 genetic models. Further subgroup meta-analysis indicated that significantly increased risks were observed among cases with a mean age <70 years (OR = 1.73, 95% CI = 1.10–2.12, P = 0.02), cases with prevalence of smoking <60% (OR = 1.39, 95% CI = 1.02–1.90, P = 0.04), and cases with aneurysm diameter ≥55 mm (OR = 1.55, 95% CI = 1.07–2.24, P = 0.02) in the dominant genetic model. No publication bias was detected in the present study.Conclusion:In conclusion, our comprehensive meta-analysis suggests that the MTHFR C677T polymorphism may play an important role in AAA susceptibility, especially in younger, non-smoking, larger AAA-diameter subgroups of patients

Association Between Leptin (-2548G/A) Genes Polymorphism and Breast Cancer Susceptibility: A Meta-Analysis.

Leptin is a confirmed breast cancer susceptibility gene. However, published studies reported mixed results. This meta-analysis was conducted to systematically get a more accurate estimation of the association between the Leptin (-2548G/A) gene polymorphism and breast cancer risk.To assess the effect of Leptin (-2548G/A) gene polymorphism on breast cancer susceptibility, we searched PUBMED, ISI Web of Knowledge, EMBASE, Chinese National Knowledge Infrastructure (CNKI) databases until September 2015 to identify eligible studies, without restriction. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the susceptibility to breast cancer. Separate analyses were conducted on features of the population such as ethnicity, source of controls, and country.A total of 9 case-control studies on Leptin (-2548G/A) gene polymorphism and breast cancer risk, including 3725 cases and 3093 case-free controls were identified. The results revealed that compared with the G allele, the A allele was associated with modestly increased risk of overall breast cancer (A vs G: OR = 1.12, 95%CI = 1.04 − 1.20, P = 0.002, PhetP < 0.00001). Following further stratified analyses, in the subgroup analyses by ethnicity, a significantly increased risk was observed among Caucasian (A vs G: OR = 1.11, 95%CI = 1.03–1.20, P = 0.006, Phet = 0.00001). No publication bias was found in the present study.In conclusion, our meta-analysis suggests that the Leptin (-2548G/A) gene polymorphism plays an important role in breast cancer susceptibility, especially in Caucasian.

Relationship of Oct-4 to malignant stage: a meta-analysis based on 502 positive/high Oct-4 cases and 522 negative/low case-free controls.

Octamer 4 (Oct-4), an important member of the POU domain transcription factor family, has been suggested to function as a master switch during differentiation of human somatic cells and more recently has come to be linked with neoplastic properties. The aim of this study was to evaluate the relationship between Oct-4 and cancer stage using a meta-analysis approach. Relevant articles published as of May 2015 were retrieved from the following databases: PubMed, ISI Web of Knowledge, Embase, and Chinese National Knowledge Infrastructure (CNKI). The strengths of relationship for outcomes of interest were estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). A total of 11 articles on Oct-4 and cancer staging that collectively included 502 positive/high Oct-4 cases and 522 negative/low case-free controls were chosen. Positive/high Oct-4 was significantly associated with cancer stage in several kinds of cancer. Specifically, positive/high Oct-4 was associated with cancer stage III/IV (fixed effects: OR = 1.53, 95% CI = 1.12-2.10), primary tumor (T3-4) (random effects: OR = 1.93, 95% CI = 0.99-3.77), and cancer grade of differentiation (intermediate-poor) (random effects: OR = 3.45, 95% CI = 1.5-7.61). These findings suggest that positive/high Oct-4 is more strongly linked to stage III/IV cancer and cancer grade of differentiation, and is correlated with malignant characteristics that lead to poor prognosis in different types of cancer, especially in Asian. Given variability related to ethnicity and differences in cancer types, additional studies are warranted to establish the generalizability of our findings.

Flap endonuclease 1 polymorphisms (rs174538 and rs4246215) contribute to an increased cancer risk: Evidence from a meta-analysis.

Flap endonuclease-1 (FEN1) is a key factor during the maintenance of genomic stability and protection against tumorigenesis. Since the identification of functional polymorphisms of FEN1 (rs174538 and rs4246215), numerous studies have evaluated the association between the two single-nucleotide polymorphisms and cancer risk. To derive a more precise estimation, a meta-analysis was performed on the association between the FEN1 polymorphisms (rs174538 and rs4246215) and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of the associations. Thirteen case-control studies, including 5,108 cases and 6,382 case-free controls, were identified. For rs174538, individuals with the GG or GA genotype had an increased risk of cancer when compared to the -69AA genotype (AA vs. GG: OR, 1.85; 95% CI, 1.65-2.08; P<0.00001; AA vs. GA: OR, 1.43; 95% CI, 1.27-1.60; P<0.00001; AA vs. GG+GA: OR, 1.28; 95% CI, 1.16-1.42; P<0.00001). For rs4246215, similar results were identified, as the GG or GT genotype was significantly associated with the increased cancer risk when compared to TT (TT vs. GG: OR, 1.71; 95% CI, 1.52-1.92; P<0.00001; TT vs. GT: OR, 1.34; 95% CI, 1.20-1.50; P<0.00001; TT vs. GG+GT: OR, 1.50; 95% CI, 1.35-1.67; P<0.00001). The present meta-analysis indicated that FEN1 rs174538 and rs4246215 polymorphisms may contribute to an increased risk of cancer.

Association of the intermediate filament nestin with cancer stage: a meta-analysis based on 223 positive/high nestin cases and 460 negative/low case-free controls.

Nestin, a member of the intermediate filament protein family, has been reported to be associated with several types of neoplastic transformation. However, questions remain, with studies reporting sometimes inconclusive or conflicting data. Thus, the aim of this study was to evaluate literature reports on the relationship between nestin and cancer stage. Relevant articles published as of June 2014 were retrieved from multiple databases. After applying specific inclusion criteria, we chose seven articles relating to nestin expression and cancer stage, which included a total of 223 positive/high nestin cases and 460 negative/low case-free controls. Overall, positive/high nestin was significantly associated with median or advanced stages of several types of cancer (nestin and cancer stage: OR = 1.90, 95% CI = 1.30-2.78; nestin and lymph node: OR = 2.17, 95% CI = 1.26-3.72). Notably, studies relating to lung cancer (three qualifying articles) showed a significant association between nestin and lung cancer stage (OR = 2.00, 95% CI = 1.16-3.44). These findings indicate that positive/high nestin may be more strongly linked to median or advanced cancer stage and correlated with malignant characteristics that lead to poor prognosis in different cancers, especially lung cancer.

Genetic association between p73 G4C14-A4T14 polymorphism and risk of squamous cell carcinoma.

This study is to evaluate the association between p73 G4C14-A4T14 polymorphism and squamous cell carcinoma (SCC) risk in diverse populations. We searched the PubMed, Embase, China National Knowledge Infrastructure, and Chinese Biomedicine databases for all articles on the association between p73 G4C14-A4T14 polymorphism and SCC risk through March 2014. We performed a comprehensive meta-analysis of six case-control studies that included 1,758 SCC cases and 2,970 case-free controls. All analyses were performed using STATA 11.0, using two-sided P values. Overall, this meta-analysis showed that the p73 G4C14-A4T14 polymorphism was associated with a significantly increased risk of SCC in three genetic models. However, after excluding one study deviating from Hardy-Weinberg equilibrium, the results then demonstrated that the p73 G4C14-A4T14 polymorphism was only associated with elevated risk of cervical squamous cell carcinoma (for AT/GC vs GC/GC: OR 1.51, 95 % CI 1.14-2.00, P heterogeneity = 0.996; for AT/AT+AT/GC vs GC/GC: OR 1.42, 95 % CI 1.08-1.87, P heterogeneity = 0.994) in subgroup analysis by tumor sites. No publication bias was found in the present study. This meta-analysis suggests that the p73 G4C14-A4T14 polymorphism is associated with an increased risk of cervical squamous cell carcinoma. Further large and well-designed studies are needed to confirm this association.

The hOGG1 Ser326Cys polymorphism contributes to digestive system cancer susceptibility: evidence from 48 case-control studies.

The Ser326Cys polymorphism in the human 8-oxogunaine DNA glycosylase (hOGG1) gene had been implicated in cancer susceptibility. Studies investigating the associations between the Ser326Cys polymorphism and digestion cancer susceptibility showed conflicting results. Therefore, a meta-analysis was performed to derive a more precise estimation of the relationship. We conducted a meta-analysis of 48 studies that included 12,073 cancer cases and 19,557 case-free controls. We assessed the strength of the association using odds ratios (ORs) with 95% confidence intervals (CIs). In our analysis, the hOGG1 Ser326Cys polymorphism was significantly associated with the risk of digestive system cancers (Cys/Cys vs. Ser/Ser: OR = 1.17, 95% CI = 1.00-1.35, P < 0.001; Cys/Cys vs. Cys/Ser + Ser/Ser: OR = 1.14, 95% CI = 1.00-1.29, P < 0.001). In subgroup analyses by cancer types, we found that the hOGG1 Ser326Cys polymorphism may increase hepatocellular cancer and colorectal cancer risks, but decrease the risk of oral cancer. These findings supported that hOGG1 Ser326Cys polymorphism may contribute to the susceptibility of digestive cancers.

Association Between Interleukin-8 –251A/T Polymorphism and Risk of Lung Cancer: A Meta-Analysis

This study is to evaluate the association between IL-8 –251A/T polymorphism and lung cancer risk in diverse populations. We performed a meta-analysis of six case-control studies that included 3,265 lung-cancer cases and 3,607 case-free controls. Overall, results showed that the IL-8 –251A/T polymorphism was not associated with a significantly increased risk of lung cancer in all genetic models. However, stratified by ethnicity, a significantly increased risk was found among Asians. In conclusion, IL-8 –251A/T polymorphism is associated with lung cancer susceptibility in Asians and the –251 A allele may increase risk of lung cancer in Asians.

Association between CLPTM1L-TERT rs401681 polymorphism and risk of pancreatic cancer: a meta-analysis.

Telomere biology plays a critical and complex role in the initiation and progression of cancer. Several recent studies have provided evidence that rs401681 polymorphisms in intronic region of cleft lip and palate trans-membrane 1-like (CLPTM1L) gene sequence are associated with pancreatic cancer (PC) development, but a comprehensive synopsis is not available. We performed a meta-analysis of 6 case-control studies that included 8,253 pancreatic cancer cases and 37,646 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 rs401681 allele T was associated with a significantly increased PC risk (OR = 1.17, 95 % CI = 1.12-1.22, P heterpgeneity = 0.596 and I (2) = 0). Similarly, in the subgroup analysis by ethnicity, a significantly increased risk was found among Asians (OR = 1.15, 95 % CI = 1.07-1.24, P heterpgeneity = 0.297 and I (2) = 8.0 %) and among Caucasian (OR = 1.13, 95 % CI = 1.02-1.26, P heterpgeneity = 0.385 and I (2) = 0). No publication bias was found in the present study. This meta-analysis suggests that T allele of CLPTM1L-telomerase reverse transcriptase rs401681 polymorphism is associated with an increased PC risk, especially among Chinese. Further large and well-designed studies are needed to confirm this association.

Association between genetic polymorphisms in AURKA (rs2273535 and rs1047972) and breast cancer risk: a meta-analysis involving 37,221 subjects.

BackgroundPublished data on the association between AURKA polymorphisms and breast cancer (BC) risk are inconclusive. This meta-analysis was performed to derive a more precise estimation on the relationship between AURKA polymorphisms (rs2273535 and rs1047972) and BC risk.MethodsPubMed, Web of Knowledge and Embase were searched for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of associations. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for allele contrast genetic model, homozygous genetic model, heterozygote genetic model, dominant model, and recessive model, respectively.ResultsA total of 13 studies (16,349 BC patients and 20,872 case-free controls) were involved in this meta-analysis. Meta-analysis showed that there was significant association between rs2273535 and BC risk in three genetic models in the overall population (A vs. T: OR = 1.08, 95% CI = 1.01–1.15, P = 0.02; AA vs. TT: OR = 1.36, 95% CI = 1.06-1.73, P < 0.00001; AA vs. TT + TA: OR = 1.15, 95% CI = 1.01-1.31, P = 0.04). In the subgroup analysis by ethnicity, the effects remained in Asians (allele contrast genetic model: OR = 1.12, 95% CI = 1.00-1.26, P = 0.04 and homozygote comparison: OR = 1.22, 95% CI = 1.06-1.41, P = 0.007). However, no genetic models reached statistical association in Cauasians. Rs1047972 polymorphism was associated with BC risk in the overall population based on homozygote comparison (AA vs. GG: OR = 0.81, 95% CI = 0.66-0.99, P = 0.04). When stratified by ethnicity, rs1047972 polymorphism had a decreased association with BC risk in Caucasians based on allele contrast genetic model, homozygote comparison, the dominant model and the recessive model. However, there was no association in any genetic model in Asians.ConclusionsThis meta-analysis suggests that AURKA rs2273535 polymorphism has an increased risk with BC, especially in Asians. However, rs1047972 polymorphism has a decreased BC risk in Caucasians. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

Effects of Interleukin-10 Polymorphisms (rs1800896, rs1800871, and rs1800872) on Breast Cancer Risk: Evidence from an Updated Meta-Analysis

The associations between Interleukin-10 (IL-10) polymorphisms and breast cancer (BC) risk are inconsistent. This study was aimed to evaluate the relationship between IL-10 polymorphisms (rs1800896, rs1800871, and rs1800872) and BC risk. Databases, including PubMed, Web of Knowledge, Embase, and Chinese National Knowledge Infrastructure, were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of associations. A total of 12 studies (4743 cancer cases and 5120 case-free controls) were eligible for meta-analysis. There were nine studies with 1851 cases and 1910 controls for rs1800896, six studies with 1034 cases and 1173 controls for rs1800871, and seven studies with 3637 cases and 3391 controls for rs1800872. Meta-analysis showed that rs1800896 and rs1800871 polymorphisms had no association with BC risk (for rs1800896: OR=1.060, 95% CI=0.785-1.432 in the dominant model, and OR=1.152, 95% CI=0.958-1.386 in the recessive model; for rs1800871: OR=0.952, 95% CI=0.859-1.056 in the dominant model, and OR=0.892, 95% CI=0.741-1.072 in the recessive model). However, rs1800872 polymorphism has association with BC risk based on the recessive model (OR=0.80, 95% CI=0.73-0.88). In the stratified analysis, when analyzed by the recessive model (CC vs. AA+AC), the ORs were 0.75 (95% CI=0.68-0.83) (p<0.00001) among Caucasians and 1.17 (95% CI=0.88-1.55) (p=0.27) among Asians. These results suggested that the CC homozygote has a 25% decreased risk of BC compared with those individuals with AA and AC genotypes in Caucasians. This meta-analysis showed that IL-10 rs1800896 and rs1800871 polymorphisms had no association with BC risk, while rs1800872 polymorphism had a decreased risk of BC in Caucasians.

Association between APE1 Single Nucleotide Polymorphism (rs1760944) and Cancer Risk: a Meta-Analysis Based on 6,419 Cancer Cases and 6,781 Case-free Controls

Apurinic/apyrimidinic endonuclease 1 (APE1) is an essential enzyme in the base excision repair pathway. Epidemiological studies have suggested associations between APE1 rs1760944 polymorphism and cancer risk. This study was aimed to evaluate the relationship between APE1 rs1760944 polymorphism and cancer risk. We searched Pubmed, ISI Web of Knowledge, Embase, Chinese National Knowledge Infrastructure (CNKI) databases until September 2013 to identify eligible studies. Odds ratios (ORs) and 95 % confidence intervals (CIs) were used to estimate the strength of the associations. 12 studies from 11 articles on APE1 rs1760944 genotypes and cancer risk were identified, including a total of 6,419 cancer cases and 6,781 case-free controls. Overall, APE1 rs1760944 polymorphism was significantly associated with the decreased risk of cancer in any genetic models (G vs. T: OR = 0.86, 95% CI = 0.82-0.90; homozygote comparison: OR = 0.74, 95% CI = 0.67-0.82; heterozygote comparison: OR =0.88, 95%CI = 0.81-0.95; dominant model TG+GG vs. TT: OR = 0.82, 95% CI = 0.76-0.89; recessive model GG vs. TT+TG: OR = 0.81, 95%CI = 0.75-0.88). In the stratified analysis by populations, the effect was remain in studies of Asian population (homozygote comparison: OR = 0.71, 95%CI = 0.63-0.79; heterozygote comparison: OR = 0.86, 95 %CI = 0.79- 0.94; dominant model: OR = 0.80, 95% CI = 0.74 -0.87 and recessive model: OR = 0.78, 95%CI = 0.71-0.86). Moreover, a significantly decreased risk was found in lung cancer studies (homozygote comparison: OR = 0.68, 95% CI = 0.59-0.79; heterozygote comparison: OR = 0.86, 95%CI = 0.77- 0.98; dominant model: OR = 0.80, 95%CI = 0.72-0.90 and recessive model: OR= 0.77, 95% CI= 0.68-0.87). These findings support that APE1 rs1760944 polymorphism has a possible protective effect on cancer susceptibility particularly among Asians. Further studies based on different ethnicity and various cancer types are warranted to verify our findings.

Hsa-miR-499 polymorphism (rs3746444) and cancer risk: A meta-analysis of 17 case–control studies

IntroductionMicroRNAs (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-499 rs3746444 polymorphism and cancer risk, which showed inconclusive results. Methodology/main resultsWe conducted a meta-analysis of 17 studies that included 7842 cancer cases and 8989 case-free controls and assessed the strength of the association, using odds ratios (ORs) with 95% confidence intervals (CIs). Overall, hsa-miR-499 rs3746444 polymorphism was associated with higher cancer risk in heterozygote model (AG vs AA, OR=1.15, 95%CI=1.01–1.30, Pheterogeneity<0.001), dominant genetic model (GG/AG vs AA, OR=1.18, 95% CI=1.04–1.33, Pheterogeneity<0.001) and allele contrast (G vs A, OR=1.09, 95% CI=1.01–1.18, Pheterogeneity=0.021). In the stratified analyses, we observed that the GG/AG genotype might modulate breast cancer risk (OR=1.13, 95% CI=1.01–1.26, Pheterogeneity=0.111) comparing with the AA genotype. Moreover, a significantly increased risk was found among Asian populations in heterozygote model (AG vs AA, OR=1.23, 95% CI=1.06–1.43, Pheterogeneity<0.001), homozygote model (GG vs AA, OR=1.22, 95% CI=1.02–1.46, Pheterogeneity=0.319), dominant model (GG/AG vs AA, OR=1.25, 95% CI=1.06–1.39, Pheterogeneity<0.001) and allele contrast (G vs A, OR=1.14, 95% CI=1.04–1.25, Pheterogeneity=0.021). ConclusionsThese findings supported that hsa-miR-499 rs3746444 polymorphism contributes to the susceptibility of cancers.

Increased Risk of Breast Cancer Associated with CC Genotype of Has-miR-146a Rs2910164 Polymorphism in Europeans

BackgroundEmerging 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 findingsWe 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/SignificanceThis 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

BackgroundMicroRNAs (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 FindingsWe 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).ConclusionsThese findings supported that hsa-miR-196a2 rs11614913 polymorphism may contribute to the susceptibility of cancers.