Lack of Association of the Cyclooxygenase-2 Gene 8473T>C Polymorphism with Breast Cancer Risk: a Meta-analysis

Background: Associations between the 8473T>C polymorphism (rs5275) in the cyclooxygenase-2 (COX-2)gene and breast cancer (BC) risk are still inconclusive and ambiguous. The aim of this meta-analysis was tocomprehensively estimate the genetic risk of 8473T>C polymorphism in the COX-2 gene for BC. Materials andMethods: We searched PubMed, Web of Science, Medline, Chinese biomedical (CBM), Weipu, China nationalknowledge infrastructure (CNKI), and Wanfang databases, covering all publications (last search was updated onAug 17, 2014). Statistical analyses were performed using Revman 5.3 and STATA 10.0 software. Results: A totalof 6,720 cases and 9,794 controls in 12 studies were included in this study. The results indicated no significantassociations between the 8473T>C polymorphism of the COX-2 gene and BC risk for the CC+TC vs TT model(pooled odds ratio (OR)=0.97, 95% confidence interval (CI)=0.90-1.03, and p=0.29). On subgroup analysis, wealso found that subdivision on ethnicity among Caucasians, Asians and others also revealed no relationshipwith BC susceptibility. With the study design (CC+TC vs TT), no significant associations were found in eitherpopulation-based case-control studies (PCC), or hospital-based case-control studies (HCC). Conclusions: Thispresent meta-analysis suggests that the 8473T>C polymorphism in the COX-2 gene is not a conspicuous lowpenetrantrisk factor for developing BC.     

Lack of Association Between the Matrix Metalloproteinase-2-1306C>T Polymorphism and Breast Cancer Susceptibility: a Meta-analysis

Background: Since inconsistent results have been reported regarding the relation between the matrix metalloproteinase-2 (MMP-2) -1306C>T polymorphism and susceptibility for breast cancer, we performed a meta-analysis to investigate the issue. Materials and Methods: An internet search of PubMed and EMBASE wasperformed to identify eligible studies. Pooled odds ratios (ORs) with their corresponding confidence intervals (CIs) were calculated to evaluate any association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility. Results: Nine case-control studies were included in the meta-analysis, involving 9,858 cases and 10,871 controls. Overall, there was no evidence of any association between the MMP-2 -1306C>T polymorphism and breast cancer susceptibility in different genetic models (T-allele vs C-allele: OR=0.95, 95%CI, 0.82-1.10, p=0.49; TT vs CC: OR=1.03, 95%CI, 0.90-1.19, p=0.66; TT+TC vs CC: OR=0.93, 95%CI, 0.78-1.10, p=0.38; TT vs TC+CC: OR=1.02, 95%CI, 0.89-1.17, p=0.77). In the subgroup analysis by ethnicity, CC was associated witha significant increase in breast susceptibility among Latin-Americans in the dominant model (OR=0.61, 95%CI,0.40-0.93, p=0.02), but the association disappeared in other models. No significant association was observed among Europeans, East Asians and others in different genetic models. In the subgroup analysis by their source of controls, no significant association between MMP-2 -1306C>T polymorphism and breast cancer susceptibility was noted among population-based studies and hospital-based studies in different genetic models. Conclusions: The results of this meta-analysis suggest that MMP-2 -1306C>T polymorphism is not associated with breast cancer susceptibility, although the association among Latin-Americans in the dominant model was significant.     

Association Between Three eNOS Polymorphisms and Cancer Risk: a Meta-analysis

Polymorphisms in the endothelial nitric oxide synthase (eNOS) gene may influence the risk of cancer, but the results are still debatable. Therefore, we performed a systematic review to provide a more complete picture and conducted a meta-analysis to derive a precise estimation. We searched PubMed, EMBASE, EBSCO, Google Scholar and China National Knowledge Infrastructure (CNKI) databases until April 2014 to identify eligible studies. Thirty-one studies with cancer patients and controls were included in the meta-analysis. Overall, thepolled analysis revealed that the T-786C polymorphism was significantly associated with increased cancer risk under multiple genetic models (C vs T: OR=1.135, 95%CI=1.048-1.228; CC vs TT: OR=1.278, 95%CI=1.045-1.562; TC vsTT: OR=1.136, 95%CI=1.023-1.261; CC+TC vs TT: OR=1.159, 95%CI=1.047-1.281; CC vs TC+TT: OR=1.204, 95%CI= 1.003-1.447). G894T was associated with significant risk for females (TT vs GG: OR=1.414, 95%CI=1.056-1.892; TT vs GT+GG: OR=1.356, 95%CI=1.108-1.661) and for breast cancer (T vs G: OR=1.097, 95%CI=1.001-1.203; TT vs GG: OR=1.346, 95%CI=1.012-1.789; TT vs GT+GG: OR=1.269, 95%CI=1.028-1.566). Increased susceptibility was revealed for prostate cancer with 4a/b (ba vs bb: OR=1.338, 95%CI=1.013-1.768; aa+ba vs bb: OR=1.474, 95%CI=1.002-2.170). This meta-analysis indicated that the eNOS T-786C polymorphism is associated with elevated cancer risk; the G894T polymorphism contributes to susceptibility to breast cancer and cancer generally in females; and the 4a/b polymorphism may be associated with prostate cancer risk.     

Matrix Metalloproteinase-2 -1306 C>T Gene Polymorphism is Associated with Reduced Risk of Cancer: a Meta-analysis

Matrix metalloproteinase-2 (MMP2) is an endopeptidase, mainly responsible for degradation of extracellularmatrix components, which plays an important role in cancer disease. A single nucleotide polymorphism (SNP)at -1306 disrupts a Sp1-type promoter site. The results from the published studies on the association betweenMMP2 -1306 C>T polymorphism and cancer risk are contradictory and inconclusive. In the present study, ameta-analysis was therefore performed to evaluate the strength of any association between the MMP2 -1306C>T polymorphism and risk of cancer. We searched all eligible studies published on association between MMP2-1306 C>T polymorphism and cancer risk in PubMed (Medline), EMBASE and Google Scholar online webdatabases until December 2013. Genotype distribution data were collected to calculate the pooled odds ratios(ORs) and 95% confidence intervals (95%CIs) to examine the strength of the association. A total of 8,590 cancercases and 9,601 controls were included from twenty nine eligible case control studies. Overall pooled analysissuggested significantly reduced risk associated with heterozygous genotype (CT vs CC: OR=0.758, 95%CI=0.637to 0.902, p=0.002) and dominant model (TT+CT vs CC: OR=0.816, 95%CI=0.678 to 0.982, p=0.032) geneticmodels. However, allelic (T vs C: OR=0.882, 95%CI=0.738 to 1.055, p=0.169), homozygous (TT vs CC: OR=1.185,95%CI=0.825 to 1.700, p=0.358) and recessive (TT vs CC+CT: OR=1.268, 95%CI=0.897 to 1.793, p=0.179)models did not show any risk. No evidence of publication bias was detected during the analysis. The results ofpresent meta-analysis suggest that the MMP2 -1306 C>T polymorphism is significantly associated with reducedrisk of cancer. However, further studies with consideration of different populations will be required to evaluatethis relationship in more detail.     

Associations Between TLR9 Polymorphisms and Cancer Risk: Evidence from an Updated Meta-analysis of 25,685 Subjects

A meta-analysis incorporating 34 case-control studies from 19 articles involving 12,197 cases and 13,488controls was conducted to assess the effects of three genetic variants of Toll-like receptor 9 (TLR9): rs187084,rs352140, and rs5743836. Studies on associations between TLR9 polymorphisms and cancer risk weresystematically searched in electronic databases. The reported odds ratios (OR) and 95% confidence intervals(CI) were pooled to assess the strength of any associations. The results showed that the rs187084 polymorphismwas significantly associated with an increased risk of cancer (CC vs TC+TT: OR=1.14, 95% CI=1.02-1.28),specifically cervical cancer (C vs T: OR=1.19, 95% CI=1.05-1.34; TC vs TT: OR=1.32, 95% CI=1.10-1.58; CCvs TT: OR=1.31, 95% CI= 1.03-1.68; CC+TC vs TT: OR=1.32, 95% CI=1.11-1.56), and that this association wassignificantly positive in Caucasians (CC vs. TC+TT: OR=1.18, 95% CI=1.01-1.38). The rs352140 polymorphismhad a protective effect on breast cancer (GA vs GG: OR=0.77, 95% CI=0.66-0.89), whereas the rs5743836polymorphism was likely protective for digestive system cancers (CC+TC vs TT: OR=0.81, 95% CI=0.66-0.98).In conclusion, our results suggest that the rs187084 polymorphism may be associated with an elevated cancerrisk, whereas polymorphisms of rs352140 and rs5743836 may play protective roles in the development of breastand digestive system cancers, respectively. From the results of this meta-analysis further large-scale case-controlstudies are warranted to verify associations between TLR9 polymorphisms and cancer.     

Association Between ERCC2 Polymorphisms and Glioma Risk: a Meta-analysis

ERCC2 is an essential component of the nucleotide excision repair pathway which is involved in the effectivemaintenance of genome integrity. Association studies on ERCC2 polymorphisms and glioma risk have yieldedinconclusive results. This meta-analysis was performed to gain a better insight into the relationship betweenERCC2 polymorphisms and glioma risk. A systematic literature search updated to December 2, 2013 wasperformed in the Pubmed and EMBASE databases. Crude pooled odds ratios (ORs) with their corresponding95% confidence intervals (95% CIs) were used to estimate the association between ERCC2 polymorphisms andglioma risk under a suitable effect model according to heterogeneity. All analyses were performed using ReviewManager 5 (version 5.2) and STATA (version 12.0). The combined results demonstrated rs13181 to be significantlyassociated with glioma risk (G allele versus T allele: OR=1.15, 95% CI=1.05–1.26, P=0.002; dominant model:OR=1.22, 95% CI=1.07–1.39, P=0.002; recessive model: OR=1.18, 95% CI=0.98–1.41, P=0.070). We also foundthat rs13181 acts in an allele dose–dependent manner (GG versus TT: OR=1.30, 95% CI=1.07–1.57, P=0.009;TG versus TT: OR=1.20, 95%=CI 1.05–1.37, P=0.009; trend test, P=0.004). However, no evidence was found inanalyses for the association between other 3 ERCC2 polymorphisms (rs238406, rs1799793, and rs1052555) andsusceptibility to glioma development. Our meta-analysis suggests that rs13181 is significantly associated withglioma risk in an allele dose–dependent manner, whereas, 3 other ERCC2 polymorphisms (rs238406, rs1799793,and rs1052555) may have no influence.     

Lack of Association Between LIG4 Gene Polymorphisms and the Risk of Breast Cancer: A HuGE Review and Meta-analysis

Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strandbreaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such asLIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology(HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJpathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphismsand susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science,Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysiswas performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios(ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final includedseven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. Theresults showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neitherincreased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium(HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer riskamong HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that thereis a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.     

Lack of any Association between Insertion/Deletion (I/D) Polymorphisms in the Angiotensin-converting Enzyme Gene and Digestive System Cancer Risk: a Meta-analysis

Objective: To investigate the association between the gene polymorphisms of angiotensin-converting enzyme(ACE) and digestive system cancer risk. Method: A search was performed in Pubmed, Medline, ISI Web ofScience and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysiswas performed by using Revman5.2 and STATA 12.0. Results: A total of 15 case-control studies comprising 2,390digestive system cancer patients and 9,706 controls were identified. No significant association was found betweenthe I/D polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53 for DD+DI vs. II). Inthe subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparisonof DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations betweenthis polymorphism and digestive system cancer risks. Conclusions: This meta-analysis suggested that the ACED/I polymorphism might not contribute to the risk of digestive system cancer.     

Lack of Association between Hsa-Mir-499 rs3746444 Polymorphism and Cancer Risk: Meta-analysis Findings

Epidemiologic findings concerning the association between the hsa-mir-499 rs3746444 A>G polymorphismand cancer risk have yielded mixed results. We aimed to investigate the association by performing a meta-analysisof all available studies. We searched PubMed and EMBASE for studies published up to November 2014, usingodds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of any association. The Benjamini-Hochberg (BH) method was used to correct the p values for multiple comparisons. We included 39 studies,including 14,136 cases and 16,937 controls. The results of overall meta-analysis suggested a borderline associationbetween hsa-mir-499 rs3746444 polymorphism and cancer susceptibility (AG+GG vs. AA: OR=1.15, 95% CI=1.04-1.26, corrected p value=0.04). After removing studies not conforming to Hardy–Weinberg equilibrium(HWE), however, this association disappeared (AG+GG vs AA: OR=1.18, 95% CI=1.03-1.34, corrected pvalue=0.21). When stratified analysis by ethnicity, cancer type or HWE in controls, although some associationsbetween hsa-mir-499 rs3746444 polymorphism and cancer susceptibility were detected, these associations nolonger existed after adjustment using BH method. In conclusion, our meta-analysis suggests that hsa-mir-499rs3746444 A>G polymorphism is not associated with risk of cancer based on current evidence.     

Meta-Analysis of Association between PALB2 Polymorphisms and Breast Cancer

Background: Previous studies have assessed associations between single nucleotide polymorphisms (SNPs) ofthe Partner and localizer of BRCA2 (PALB2) gene and risk of breast cancer. However, the results of these studiesare not consistent. Materials and Methods: We designed a meta-analysis to obtain a more reliable appraisal ofthe association between SNPs in the PALB2 gene and the susceptibility to breast cancer. We searched PubMed, Googlescholar and Embase databases and selected six studies with sufficient data to estimate the pooled odds ratios (ORs)and 95% confidence intervals (CIs). Results: Statistical analyses showed that the rs120963 was associated with breastcancer risk in allelic (OR (95% CI) = 1.33 (1.18-1.49)), homozygous (OR (95% CI) = 1.74 (1.31-2.32)), dominant(OR (95% CI) = 1.42 (1.22, 1.65)) and recessive (OR (95% CI) = 1.54 (1.17, 2.03)) models. The rs249954 andrs16940342 were associated with breast cancer risk in allelic (OR (95% CI) = 1.13 (1.04, 1.23) and 1.12 (1.01, 1.24)respectively) and dominant (OR (95% CI) = 1.23 (1.09, 1.39) and 1.18 (1.04, 1.33) respectively) models. The rs249935and rs447529 SNPs were associated with breast cancer in homozygous (OR (95% CI) = 0.67 (0.46, 0.97) and 0.51(0.30, 0.89) respectively) and recessive (OR (95% CI) = 0.65 (0.45, 0.95) and 0.51 (0.30, 0.88) respectively) models.Conclusions: The current meta-analysis shows the associations between five SNPs of PALB2 and breast cancer riskand confirms the results of previous studies regarding the role of this gene in the pathogenesis of breast cancer.     

Association of XRCC1 Arg399Gln Polymorphism with Colorectal Cancer Risk: A HuGE Meta Analysis of 35 Studies

Background: Non-synonymous polymorphisms in XRCC1 hase been shown to reduce effectiveness of DNArepair and be associated with risk of certain cancers. In this study we aimed to clarify any association betweenXRCC1 Arg399Gln and colorectal cancer (CRC) risk by performing a meta-analysis of published case-controlstudies. Materials and Methods: PubMed and Google Scholar were searched to explore the association betweenXRCC1 and CRC. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate theassociation strength. Publication bias was assessed by Egger’s and Begg’s tests. Results: Up to January 2015, 35case control studies involving 9,114 CRC cases and 13,948 controls were included in the present meta-analysis.The results showed that the Arg399Gln polymorphism only under an allele genetic model was associated withCRC risk (A vs. G: OR 0.128, 95% CI 0.119-0.138, p<0.001). Also, this meta-analysis suggested that the XRCC1Arg399Gln polymorphism might associated with susceptibility to CRC in Asians (A vs G: OR 0.124, 95% CI0.112-0.138, p<0.001) and Caucasian (A vs G: OR 0.132, 95% CI 0.119-0.146, p<0.001) only under an allele geneticmodel. Conclusions: This meta-analysis confirms the association between XRCC1 Arg399Gln polymorphismand CRC risk and suggests that the heterogeneity is not strongly modified by ethnicity and deviation from theHardy-Weinberg equilibrium.     

Updated Meta-analysis of the Association Between CYP2E1 RsaI/PstI Polymorphisms and Lung Cancer Risk in Chinese Population

Background: A number of studies have reported relationships of CYP2E1 RsaI/PstI polymorphisms with susceptibility to lung cancer in Chinese population. However, the epidemiologic results have been conflictive rather than conclusive. The purpose of this study was to address the associations of CYP2E1 RsaI/PstI polymorphisms with lung cancer risk in Chinese population comprehensively. Materials and Methods: Systematic searches were conducted in the PubMed, Science Direct, Elsevier, CNKI and Chinese Biomedical Literature Databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of association. Results: Overall, we observed a decreased lung cancer risk among subjects carrying CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 genotypes (OR=0.76, 95%CI: 0.64-0.90 and OR=0.78, 95%CI: 0.66-0.93, respectively), as compared with subjects carrying the c1/c1 genotype. In subgroup analysis, we observed a decreased lung cancer risk among c1/c2 carriers in hospital-based studies (OR=0.81, 95%CI: 0.68-0.98) and among carriers with c1/c2 and c1/c2+c2/c2 genotypes in population-based studies(OR=0.57, 95%CI: 0.42-0.79 and OR=0.58, 95%CI: 0.43-0.79, respectively), as compared with subjects carrying the c1/c1 genotype. Limiting the analysis to studies with controls in Hardy-Weinberg equilibrium (HWE), we similarly observed a decreased lung cancer risk among c1/c2 and c1/c2+c2/c2 carriers (OR=0.73, 95%CI: 0.60-0.88 and OR=0.73, 95%CI: 0.60-0.88, respectively), as compared with c1/c1. Conclusions: Our results suggested that CYP2E1 RsaI/PstI c1/c2 and c1/c2+c2/c2 variants might be a protective factor for developing lung cancer in Chinese population. Further well-designed studies with larger sample size are required to verify our findings.     

Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

Background: Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancershave been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma(CC-RCC) remains unknown. The aim of this study was to explore any relation. Materials and Methods: Thestudy population consisted of 77 patients with CC-RCC and 161 healthy control subjects. Polymorphism analysesof Lys109Arg and Gln223Arg were performed by direct DNA sequencing and PCR-restriction fragment lengthpolymorphism approaches respectively. Results: Comparisons of allelic and genotypic frequencies in Lys109Argand Gln223Arg showed no significant difference between the cases and controls. However, when evaluating thecombined genotype of Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30)and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of the latter could notbe calculated for a value of zero) . Furthermore, the G-G haplotype frequency of Lys109Arg and Gln223Arg inthe cases was higher (OR=1.68; 95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in thecases were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI of the latter couldnot be calculated for a value of zero). In addition, the Lys109Arg A allele was in LD with the Gln223Arg A allele(d’=0.9399) in the CC-RCC subjects, but not in the controls. Conclusions: Our data suggest that the GG/GGcombined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as evaluating factors for CC-RCCrisk.     

Association of Functional Polymorphisms of the XRCC4 Gene with the Risk of Breast Cancer: A Meta-analysis

Objective: X-ray cross-complementing group 4 (XRCC4) is a major repair gene for DNA double-strand breaks(DSB) in the non-homologous end-joining (NHEJ) pathway. Several potentially functional polymorphisms of theXRCC4 gene have been implicated in breast cancer risk, but individually published studies showed inconclusiveresults. The aim of this meta-analysis was to investigate the association between XRCC4 polymorphisms and therisk of breast cancer. Methods: The MEDLINE, EMBASE, Web of science and CBM databases were searchedfor all relevant articles published up to June 20, 2012. Potential associations were assessed with comparisons ofthe total mutation rate (TMR), complete mutation rate (CMR) and partial mutation rate (PMR) in cases andcontrols. Statistical analyses were performed using RevMan 5.1.6 and STATA 12.0 software. Results: Five studieswere included with a total of 5,165 breast cancer cases and 4,839 healthy controls. Meta-analysis results showedthat mutations of rs2075686 (C>T) and rs6869366 (G>T) in the XRCC4 gene were associated with increasedrisk of breast cancer, while rs2075685 (G>T) and rs10057194 (A>G) might decrease the risk of breast cancer.However, rs1805377 (A>G), rs1056503 (G>T), rs28360317 (ins>del) and rs3734091 (A>G) polymorphisms ofXRCC4 gene did not appear to have an influence on breast cancer susceptibility. Conclusion: Results from thecurrent meta-analysis suggest that the rs2075685 (G>T) and rs6869366 (G>T) polymorphisms of the XRCC4 genemight increase the risk of breast cancer, whereas rs2075685 (G>T) and rs10057194 (A>G) might be protectivefactors.     

N-Acetyltransferase 2 Gene Polymorphisms are Associated with Susceptibility to Cancer: a Meta-analysis

N-acetyltransferase 2 (NAT2) is a polymorphic enzyme that plays an important role in the metabolism ofvarious potential carcinogens. In recent years, a number of studies have been carried out to investigate therelationship between the rs1799930 and rs1799931 polymorphism in NAT2 and cancer risk in multiple populationsfor different types of cancer. However, the results were not consistent. Therefore, we performed a meta-analysisto further explore the relationship between NAT2 polymorphism and the risk of cancer. A total of 21 studiesinvolving 15, 450 subjects for rs1799930 and 13, 011 subjects for rs1799931 were included in this meta-analysis.Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of associations. Wealso evaluated the publication bias and performed a sensitivity analysis. Overall, our results showed an apparentsignificant association between the NAT2 rs1799930 polymorphism and cancer susceptibility in Asians (GAvs. GG: OR=1.22, 95% CI=1.03-1.45; dominant model: OR=1.22, 95% CI=1.03-1.43) and population-basedcontrols (GA vs. GG: OR=1.10, 95% CI=1.01-1.19; dominant model: OR=1.09, 95% CI=1.01-1.18). In contrast,a significant association was observed between the NAT2 rs1799931 G>A polymorphism and decreased cancersusceptibility in overall meta-analysis (AA vs. GG: OR=0.55, 95% CI=0.33-0.93; GA vs. GG: OR=1.00, 95%CI=0.88-1.14; dominant model: OR=0.97, 95% CI=0.86-1.10; recessive model: OR=0.56, 95% CI=0.34-0.94)and the Asian group (AA vs. GG: OR=0.50, 95% CI=0.26-0.94; recessive model, OR=0.50, 95% CI=0.27-0.94).We found that the NAT2 rs1799930 may be a risk factor, while the NAT2 rs1799931 polymorphism is associatedwith a decreased risk of cancer and is likely a protective factor against cancer development.     

Associations Between Three Polymorphisms in the Interleukin-4 Receptor Gene and Risk of Cancer: a Meta-analysis

Interleukin-4 receptor (IL-4R) gene single nucleotide polymorphisms (SNPs) are implicated in cancerdevelopment. However, results from the published reports have remained inconclusive. The objective of thisstudy was to conduct a meta-analysis investigating the association between polymorphisms in IL-4R gene andcancer risk. Pubmed, EMBASE and China National Knowledge Infrastructure (CNKI) were searched for casecontrolstudies published up to October 30, 2012 that investigated IL-4R polymorphisms and cancer risk. Oddsratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of any associations. ThreeIL-4R polymorphisms (Q576R, rs1801275; I75V, rs1805010; S503P, rs1805015) in 21 case-control studies wereanalyzed. Our meta-analysis indicated that these three polymorphisms are not associated with cancer risk whenall studies were pooled together. In the subgroup analysis by tumor site, the results showed that Q576R G allelecarriers were associated with a significantly decreased cervical cancer risk (recessive model: OR = 0.77, 95%CI= 0.60-0.98; homozygote comparison: OR = 0.76, 95%CI = 0.58-0.98). I75V G allele carriers were associatedwith a decreased risk of renal cancer (dominant model = 0.71, 95%CI = 0.57-0.89, heterozygote comparison:OR = 0.69, 95%CI = 0.55-0.87). When stratified by ethnicity, Q576R G allele carriers were associated with adecreased cancer risk in Caucasians (dominant model: OR = 0.90, 95%CI = 0.83-0.98; heterozygote comparison:OR = 0.89, 95%CI = 0.82-0.98). I75V G allele carriers were associated with a decreased cancer risk in Asians(heterozygote comparison: OR = 0.76, 95%CI = 0.62-0.94). S503P C allele carriers were also associated with adecreased cancer risk in Asians (CC VS TT: OR = 0.29, 95%CI = 0.08-0.99). Our results suggest that Q576R,I75V and S503P may be associated with a decreased cancer risk for certain types of cancers and in some specificethnic groups. Future case-control studies with large sample size are needed to evaluate these associations indetail.     

Association Between VDR Polymorphisms and Breast Cancer: An Updated and Comparative Meta-analysis of Crude and Adjusted Odd Ratios

There is a lot of debate on the relationship between vitamin D receptor polymorphisms and risk of breastcancer. Herein, we quantitatively analyzed the published case-control studies on this relationship by metaanalysis,performing a bibliographic search from Pubmed and CNKI up to July 31, 2013. The included casecontrolstudies for Fok1, Bsm1, Taq1, Apa1, Cdx2 and Poly-A were 16, 19, 20, 10, 4, 6, respectively. Crude andadjusted odd ratios and 95% confidence intervals were calculated to present and compare the strength of anyassociations. The results of combined analyses indicated that Fok1, Bsm1, Apa1, Cdx2 and Poly-A were notsignificantly associated with the risk of breast cancer. In contrast, the tt genotype of Taq1 was a modest riskfactor for breast cancer development (tt vs. TT: OR = 1.21, 95% CI: 1.01-1.44). To further confirm the aboveresults, adjusted effects for the six polymorphisms were pooled based on adjusted ORs reported in the originalstudies. Adjusted ORs of Fok1, Apa1, Cdx2 and Poly-A were similar to the crude ORs. However, Bsm1 and Taq1showed inconsistent results. For Bsm1, OR for BB vs. bb was 0.85, 95% CI: 0.74-0.98; for Taq1, OR for tt vs.TT was 1.03, 95% CI: 0.92-1.15, and not associated with risk. Subgroup analyses for crude ORs showed someassociation between Bsm1, Taq1 and breast cancer in Caucasians only, but for adjusted ORs, no associationswere found. This meta-analysis suggests that the roles that Fok1, Apa1, Cdx2 and Poly-A polymorphisms play inbreast cancer risk are negligible, with Bsm1 and Taq1 as possible exceptions. To be conservative, we still assumedthat they may play a modest role in determining breast cancer risk. Further studies are needed to validate ourfindings.     

Four Polymorphisms in the Cytochrome P450 1A2 (CYP1A2) Gene and Lung Cancer Risk: a Meta-analysis

Background: Previous published data on the association between CYP1A2 rs762551, rs2069514, rs2069526,and rs2470890 polymorphisms and lung cancer risk have not allowed a definite conclusion. The present metaanalysisof the literature was performed to derive a more precise estimation of the relationship. Materials andMethods: 8 publications covering 23 studies were selected for this meta-analysis, including 1,665 cases and 2,383controls for CYP1A2 rs762551 (from 8 studies), 1,456 cases and 1,792 controls for CYP1A2 rs2069514 (from 7studies), 657 cases and 984 controls for CYP1A2 rs2069526 (from 5 studies) and 691 cases and 968 controls forCYP1A2 rs2470890 (from 3 studies). Results: When all the eligible studies were pooled into the meta-analysisfor the CYP1A2 rs762551 polymorphism, significantly increased lung cancer risk was observed in the dominantmodel (OR=1.21, 95 % CI=1.00-1.46). In the subgroup analysis by ethnicity, significantly increased risk of lungcancer was observed in Caucasians (dominant model: OR=1.29, 95%CI=1.11-1.51; recessive model: OR=1.33,95%CI=1.01-1.75; additive model: OR=1.49, 95%CI=1.12-1.98). There was no evidence of significant associationbetween lung cancer risk and CYP1A2 rs2069514, s2470890, and rs2069526 polymorphisms. Conclusions: Insummary, this meta-analysis indicates that the CYP1A2 rs762551 polymorphism is linked to an increased lungcancer risk in Caucasians. Moreover, our work also points out the importance of new studies for rs2069514associations in lung cancer, where at least some of the covariates responsible for heterogeneity could be controlled,to obtain a more conclusive understanding about the function of the rs2069514 polymorphism in lung cancerdevelopment.     

Updated Meta-analysis on HER2 Polymorphisms and Risk of Breast Cancer: Evidence from 32 Studies

Background: Several studies have been performed to investigate the association of the HER2 Ile655Valpolymorphism and breast cancer risk. However, the results were inconsistent. To understand the preciserelationship, a meta-analysis was here conducted. Materials and Methods: A search of PubMed conducted toinvestigate links between the HER2 Ile655Val polymorphism and breast cancer, identified a total of 32 studies, ofwhich 29, including 14,926 cases and 15,768 controls, with odds ratios (ORs) with 95% confidence intervals wereused to assess any association. Results: In the overall analysis, the HER2 Ile655Val polymorphism was associatedwith breast cancer in an additive genetic model (OR=1.136, 95% CI 1.043-1.239, p=0.004) and in a dominantgenetic (OR=1.118, 95% CI 1.020-1.227, p=0.018), while no association was found in a recessive genetic model.On subgroup analysis, an association with breast cancer was noted in the additive genetic model (OR=1.111,95% CI: 1.004-1.230, p=0.042) for the Caucasian subgroup. No significant associations were observed in Asiansand Africans in any of the genetic models. Conclusions: In summary, our meta-analysis findings suggest thatthe HER2 Ile655Val polymorphism is marginally associated with breast cancer susceptibility in worldwidepopulations with additive and dominant models, but not a recessive model.     

Association Between MDM2 SNP309 T>G and Risk of GastricCancer: A Meta-analysis

Background: As a negative regulator of P53, MDM2 plays an important role in carcinogenesis; a polymorphismin its promoter region. SNP309 T>G, is known to increase the expression of MDM2, thus being considered relatedto higher susceptibility to neoplasia. However, no agreement has been achieved regarding its effects on gastriccancer. Methods: The present systematic meta-analysis was performed based on comprehensive literature searchfrom Pubmed, Web of science and CBM databases. Results: It was suggested from 6 independent studies thatthe GG genotype is associated with a significantly increased risk of gastric cancer (Recessive: OR = 1.43, 95%CI = 1.08-1.91, P = 0.013), and subgroup analysis also confirmed the relationship (English publications-recessivemodel: OR = 1.45, 95% CI = 1.10-1.91, P = 0.009; Studies in China-recessive model: OR = 1.58, 95% CI =1.08-2.30, P = 0.017). No publication bias was detected. Conclusion: The meta-analysis indicated a significantinverse association between GG genotype carriage and elevated risk of gastric cancer. However, more studiesand detailed information are needed to fully address the topic.