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 of the PTEN IVS4 (rs3830675) Gene Polymorphism with Reduced Risk of Cancer: Evidence from a Meta-analysis

PTEN (phosphatase and tensin homologue), as a tumor suppressor gene, plays a significant role in regulatingcell growth, proliferation, and apoptosis. Results from published studies for association between the PTEN IVS4I/D (rs3830675) polymorphism and cancer risk are inconsistent and inconclusive. We therefore conducted ameta-analysis to evaluate the potential association between PTEN IVS4 I/D polymorphism and risk of cancerin detail. We searched PubMed (Medline) and EMBASE web databases to cover all relevant studies publisheduntil December 2013. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidenceintervals (95%CIs) were used to appraise the strength of association. A total of 1,993 confirmed cancer casesand 3,200 controls were included from six eligible case-control studies. Results from overall pooled analysissuggested a significant effect of the PTEN IVS4 I/D polymorphism and cancer risk in all genetic models, i.e.,allele (I vs D: OR=0.743, 95%CI=0.648 to 0.852, p=0.001), homozygous (II vs DD: OR=0.673, 95%CI=0.555 to0.816, p=0.001), heterozygous (ID vs DD: OR=0.641, 95%CI=0.489 to 0.840, p=0.001), dominant (II+ID vs DD:OR=0.626, 95%CI=0.489 to 0.802, p=0.001) and recessive (II vs DD+ID: OR=0.749, 95%CI=0.631 to 0.889,p=0.001). Significant publication bias was detected during the analysis. The present meta-analysis suggests thatthe PTEN IVS4 I/D polymorphism is significantly associated with reduced risk of cancer. However, future largerstudies with other groups of populations are warranted to clarify this association.     

Methionine Synthase Reductase A66G Polymorphism is not Associated with Breast Cancer Susceptibility - a Meta-analysis

Background: Several studies have investigated the association between methionine synthase reductase(MTRR) A66G polymorphism and breast cancer risk, but controversial results were yielded. Therefore, weperformed a meta-analysis to provide a more robust estimate of the effect of this polymorphism on susceptibilityto breast cancer. Materials and Methods:Case-control studies investigating the relationship between MTRRA66G polymorphism and breast cancer risk were included by searching PubMed, EMBASE, China NationalKnowledge Infrastructure and Wanfang Database. Either fixed-effects or random-effects models were appliedto calculate odds ratios(ORs) and 95% confidence intervals (CIs) by RevMan5.2 software. Results: A total of9 studies bearing 7,097 cases and 7,710 controls were included in the meta-analysis. The results were that thecombined ORs and 95%CIs of MTRR 66AG, GG, (AG+GG) genotypes were 0.98(0.91-1.05), 1.06(0.97-1.16)and 1.02(0.94-1.10), respectively with p=0.52, 0.19 and 0.65. We also performed subgroup analysis by specificethnicity. The results of the combined analysis of MTRR 66AG, GG, (AG+GG) genotypes and breast cancer inAsian descent were Z=0.50, 0.53 and 0.21, with p all>0.05; for breast cancer in Caucasian descent, the results wereZ=1.14, 1.65 and 0.43, with p all>0.05. Conclusions: Our findings suggested that MTRR A66G polymorphismwas not associated with breast cancer susceptibility.     

E-Selectin S128R Polymorphism is Associated with Cancer Risk: a Meta-analysis

Background: Genetic factors have been shown to play an important role in the development of cancers.However, individual studies may fail to completely demonstrate complicated genetic relationships because ofsmall sample size. Therefore, we performed a meta-analysis to evaluate the association of E-selectin Ser128Arg(S128R) with cancer risk. Materials and Methods: A literature search in PubMed, Embase, Web of Science,Science Direct, SpringerLink, EBSCO, Wanfang, and Chinese National Knowledge Infrastructure databaseswas carried out to identify studies of the association between E-selectin S128R polymorphism and cancer risk.The odds ratio (OR) with 95% confidence intervals (95%CIs) were used to assess the strength of association.Results: A total of eight studies involving 1,675 cancer cases and 2,285 controls were included in the meta-analysis.In overall populations, S128R polymorphism seemed to be associated with cancer risk (Arg allele vs Ser allele:OR=1.65, 95%CI =1.33-2.04, p<0.01; Arg/Arg+Arg/Ser vs Ser/Ser: OR=1.87, 95%CI =1.48-2.36, p<0.01; Arg/Servs Ser/Ser: OR=1.80, 95%CI =1.51-2.14, p<0.01). Similarly, subgroup analysis by ethnicity and source of controlalso revealed that this polymorphism was related to cancer risk. Conclusions: Our meta-analysis revealed thatthere was association between the E-selectin S128R polymorphism and the risk of cancer. Further large andwell-designed studies are needed to confirm this association.     

Matrix Metalloproteinase-2 (-1306 C>T) Promoter Polymorphism and Risk of Colorectal Cancer in the Saudi Population

Background: Matrix metalloproteinase-2 (MMP-2) is an enzyme with proteolytic activity against matrixproteins, particularly basement membrane constituents. A single nucleotide polymorphism (SNP) at -1306,which disrupts a Sp1-type promoter site (CCACC box), results in strikingly lower promoter activity with theT allele. In the present study, we investigated whether this MMP-2 genetic polymorphism might be associatedwith susceptibility to colorectal cancer (CRC) in the Saudi population. We also analyzed MMP-2 gene expressionlevel sin CRC patients and 4 different cancer cell lines. Materials and Methods: TaqMan allele discriminationassays and DNA sequencing techniques were used to investigate the C-1306T SNP in the MMP-2 gene of Saudicolorectal cancer patients and controls. The MMP-2 gene expression level was also determined in 12 coloncancer tissue samples collected from unrelated patients and histologically normal tissues distant from tumormargins. Results and Conclusions: The MMP-2 C-1306T SNP in the promoter region was associated with CRC inour Saudi population and the MMP-2 gene expression level was found to be 10 times higher in CRC patients.The MMP-2 C-1306T SNP is significantly associated with CRC in the Saudi population and this finding suggestedthat MMP-2 variants might help predict CRC progression risk among Saudis. We propose that analysis of thisgene polymorphism could assist in identification of patient subgroups at risk of a poor disease outcome.     

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.     

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.     

The NAD(P)H: Quinine Oxidoreductase 1 (NQO1) Gene 609 C>T Polymorphism is Associated with Gastric Cancer Risk: Evidence from a Case-control Study and a Meta-analysis

The association between the NAD(P)H:quinone oxidoreductase 1 (NQO1) gene C609T polymorphism(rs1800566) and gastric cancer has been widely evaluated, but a definitive answer is so far lacking. We firstconducted a case-control study to assess this association in a large Han Chinese population, and then performeda meta-analysis to further address this issue. Although our case-control association study indicated no significantdifference in the genotype and allele distributions of C609T polymorphism between gastric cancer patientsand controls, in the meta analysis involving 4,000 subjects, comparison of alleles 609T and 609C indicated asignificantly increased risk (46%) for gastric cancer (95% confidence interval (95%CI) for odds ratio (OR)=1.20-1.79) in individuals with the T allele. The tendency was similar to the homozygote (OR=1.81, 95%CI: 1.16-2.84),dominant models (OR=1.41, 95%CI: 1.12-1.79), as well as recessive model (OR=1.58, 95%CI: 1.06-2.35). Stratifiedanalysis by study design demonstrated stronger associations in population-based than in hospital-based studies.And ethnicity-based analysis demonstrated a significant association in Asians. We conclude that the NQO1 geneC609T polymorphism increases the risk for gastric cancer, especially in Asian populations.     

G894T and 4a/b Polymorphisms of NOS3 Gene are Not Associated with Cancer Risk: a Meta-analysis

Endothelial nitric oxide synthase (eNOS or NOS3) produces nitric oxide and genetic polymorphisms ofNOS3 gene play significant roles in various processes of carcinogenesis. The results from published studies onthe association between NOS3 G894T and NOS3 intron 4 (4a/b) polymorphisms and cancer risk are conflictingand inconclusive. However, i n order to assess this relationship more precisely, a meta-analysis was performedwith PubMed (Medline), EMBASE and Google web searches until February 2014 to select all published casecontroland cohort studies. Genotype distribution data were collected to calculate the pooled odd ratios (ORs) and95% confidence intervals (CIs) to evaluate the strength of association. A total of 10,546 cancer cases and 10,550controls were included from twenty four case-control studies for the NOS3 G894T polymorphism. The resultsindicated no significant association with cancer risk as observed in allelic (T vs G: OR=1.024, 95%CI=0.954to 1.099, p=0.508), homozygous (TT vs GG: OR=1.137, 95%CI=0.944 to 1.370, p=0.176), heterozygous (GT vsGG: OR=0.993, 95%CI=0.932 to 1.059, p=0.835), recessive (TT vs GG+GT: OR=1.100, 95%CI=0.936 to 1.293,p=0.249) and dominant (TT+GT vs GG: OR=1.012, 95%CI=0.927 to 1.105, p=0.789) genetic models. Similarly,a total of 3,449 cancer cases and 3,691 controls were recruited from fourteen case-control studies for NOS3 4a/bpolymorphism. Pooled results indicated no significant association under allelic (A vs B: OR=0.981, 95%CI=0.725to 1.329, p=0.902), homozygous (AA vs BB: OR=1.166, 95%CI=0.524 to 2.593, p=0.707), heterozygous (BA vsBB: OR=1.129, 95%CI=0.896 to 1.422, p=0.305), dominant (AA+BA vs BB: OR=1.046, 95%CI=0.779 to 1.405,p=0.763) and recessive (AA vs BB+BA: OR=1.196, 95%CI=0.587 to 2.439, p=0.622) genetic contrast models. Thismeta-analysis suggests that G894T and 4a/b polymorphisms of NOS3 gene are not associated with increased ordecreased risk of overall cancer.     

The -765G>C Polymorphism in the Cyclooxygenase-2 Gene and Digestive System Cancer: a Meta-analysis

Background: Published data regarding associations between the -765G>C polymorphism in cyclooxygenase-2(COX-2) gene and digestive system cancer risk have been inconclusive. The aim of this study was to comprehensivelyevaluate the genetic risk of the -765G>C polymorphism in the COX-2 gene for digestive system cancer. Materialsand Methods: A search was performed in Pubmed, Medline (Ovid), Embase, CNKI, Weipu, Wanfang and CBMdatabases, covering all studies until Feb 10, 2014. Statistical analysis was performed using Revman5.2. Results:A total of 10,814 cases and 16,174 controls in 38 case-control studies were included in this meta-analysis. Theresults indicated that C allele carriers (GC+CC) had a 20% increased risk of digestive system cancer whencompared with the homozygote GG (odds ratio (OR)=1.20, 95% confidence interval (CI), 1.00-1.44 for GC+CCvs GG). In the subgroup analysis by ethnicity, significant elevated risks were associated with C allele carriers(GC+CC) in Asians (OR = 1.46, 95% CI=1.07-2.01, and p=0.02) and Africans (OR=2.12, 95% CI=1.57-2.87, andp< 0.00001), but not among Caucasians, Americans and mixed groups. For subgroup analysis by cancer type(GC+CC vs GG), significant associations were found between the -765G>C polymorphism and higher risk forgastric cancer (OR=1.64, 95% CI=1.03-2.61, and p=0.04), but not for colorectal cancer, oral cancer, esophagealcancer, and others. Regarding study design (GC+CC vs GG), no significant associations were found in thenpopulation-based case-control (PCC), hospital-based case-control (HCC) and family-based case-control (FCC)studies. Conclusions: This meta-analysis suggested that the -765G>C polymorphism of the COX-2 gene is apotential risk factor for digestive system cancer in Asians and Africans and gastric cancer overall.     

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.     

The 765G>C Polymorphism in the Cyclooxygenase-2 Gene and Gastric Cancer Risk: an Update by Meta-analysis

Background: The 765G>C polymorphism in cyclooxygenase-2 (COX-2) gene has been extensively investigatedfor association with gastric cancer (GC). However, the results of different studies have been inconsistent. The aimof this study is to comprehensively evaluate the genetic risk of -765G>C polymorphism in the COX-2 gene forGC. Materials and Methods: We searched Pubmed, Embase, Medline, CNKI database, Wanfang database, Weipudatabase, and Chinese Biomedical database, covering all publications (last search been performed on Jan 10,2014). Statistical analyses were performed using Revman 5.2 and STATA 10.0 software. Results: A total of 1,874cases and 3,005 controls in 10 case-control studies were included in this meta-analysis. The results indicated thatthe variant C allele carriers (GC+CC) had a 69% increased risk of GC when compared with the homozygote GG(odds ratio (OR)=1.69, 95% confidence interval (CI), 1.10-2.61 for GC+CC vs GG). In the subgroup analysis byethnicity, significant elevated risks were associated with C allele carriers in Asians (OR=1.75, 95%CI=1.40-2.18,and p<0.00001) and in Indians (OR=8.38, 95%CI=4.34-16.16, and p<0.00001) but not in Caucasians (OR=1.07,95%CI=0.81-1.42, and p=0.62) or in Dutch (OR=0.53, 95%CI= 0.33-0.87, and p= 0.01).In the subgroup analysisby Helicobacter pylori (H. pylori) status, a significantly increased risk was identified among H. pylori (+) (OR=3.58,95%CI=2.33-3.50, and p<0.00001) and H. pylori (-) (OR=2.32, 95%CI=1.46-3.69, and p=0.0004). Conclusions:This meta-analysis suggested that the -765G>C polymorphism in the COX-2 gene could be a risk factor for GCin Asians and Indians.     

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.     

Association of Matrix Metalloproteinase1-1607 1G>2G Polymorphism and Lung Cancer Risk: An Update by Meta-Analysis

Objective: The association between matrix metalloproteinase1 (MMP1)-1607 1G>2G polymorphism and lung cancerrisk is still inconclusive and inconsistent. We conducted a meta-analysis to estimate the potential relationship betweenMMP1-1607 1G>2G polymorphism and lung cancer risk. Methods: The comprehensive searches of the PubMed, Webof Science, Medline, CBM, CNKI, Weipu, and Wanfang databases, published up to Nov 10, 2018. Statistical analyseswere performed with Review Manager 5.3 software. Results: A total of 14 relevant studies containing 6068 cases and5860 controls were included in the study. The results indicated that MMP1-1607 1G>2G polymorphism was significantlyassociated with increased lung cancer risk under four models: 2G vs. 1G model (pooled OR = 1.19, 95% CI = 1.05-1.34,P < 0.0001); 2G/2G vs. 1G/1G (pooled OR = 1.34, 95% CI = 1.09-1.64, P = 0.003); 2G/2G vs. 1G/1G+1G/2G (pooledOR = 1.26, 95% CI = 1.06-1.49, P < 0.0001); 2G/2G+1G/2G vs. 1G/1G (pooled OR = 1.21, 95% CI = 1.05-1.40, P= 0.01). Subgroup analyses showed that there was a higher increase in smoking status under three models: 2G/2Gvs. 1G/1G (pooled OR = 2.07, 95% CI = 1.14-3.77, P = 0.02); 2G/2G vs. 1G/1G+1G/2G (pooled OR = 1.71, 95% CI= 1.17-2.52, P = 0.006); 2G/2G+1G/2G vs. 1G/1G (pooled OR = 2.03, 95% CI = 1.14-3.62, P = 0.02). In addition,subgroup analyses by ethnicity further identified the significant association in Asians. Non-smoking population andethnicity among Caucasian had no relationship with lung cancer susceptibility in four models. Conclusion: Our studysuggested that MMP1-1607 1G>2G polymorphism was a risk factor for developing lung cancer risk.     

CYP2E1 RsaI/PstI Polymorphism and Liver Cancer Risk among East Asians: a Huge Review and Meta-analysis

Published data on any association between the CYP2E1 RsaI/PstI (c1/c2) polymorphism and liver cancer riskamong east Asians are inconclusive. The aim of this Human Genome Epidemiology (HuGE) review and metaanalysiswas to derive a more precise estimation of the relationship. A literature search of Pubmed, Embase, Webof science and CBM databases from inception through July 2012 was conducted. Twelve case-control studies wereincluded with a total of 1,552 liver cancer cases and 1,763 healthy controls. Crude odds ratios (ORs) with 95%confidence intervals (CIs) were used to assess the strength of association under five genetic models. When all theeligible studies were pooled into the meta-analysis, the results showed that the c2 allele and the c2 carrier (c2/c2+ c2/c1) of RsaI/PstI polymorphism were associated with decreased risk of liver cancer among east Asians (c2vs. c1: OR = 0.75, 95%CI: 0.59-0.95, P = 0.016; c2/c2 + c2/c1 vs. c1/c1: OR = 0.76, 95%CI: 0.58-1.00, P = 0.050).In the stratified analysis by country, significant associations were observed between RsaI/PstI polymorphismand decreased risk of liver cancer among the Chinese population (c2 vs. c1: OR = 0.70, 95%CI: 0.54-0.91, P =0.007; c2/c2 + c2/c1 vs. c1/c1: OR = 0.72, 95%CI: 0.54-0.95, P = 0.020), but not among Japanese and Koreanpopulations. Results from the current meta-analysis indicates that the c2 allele of CYP2E1 RsaI/PstI (c1/c2)polymorphism may be a protective factor for HCC among east Asians, especially among China populations.     

The DNA Repair Gene ERCC6 rs1917799 Polymorphism is Associated with Gastric Cancer Risk in Chinese

Objective: Excision repair cross-complementing group 6 (ERCC6) is a major component of the nucleotideexcision repair pathway that plays an important role in maintaining genomic stability and integrity. Severalrecent studies suggested a link of ERCC6 polymorphisms with susceptibility to various cancers. However, therelation of ERCC6 polymorphism with gastric cancer (GC) risk remains elusive. In this sex- and age- matchedcase-control study including 402 GC cases and 804 cancer-free controls, we aimed to investigate the associationbetween a potentially functional polymorphism (rs1917799 T>G) in the ERCC6 regulatory region and GC risk.Methods: The genotypes of rs1917799 were determined by Sequenom MassARRAY platform and the status ofHelicobacter pylori infection was detected by enzyme-linked immunosorbent assay. Odd ratios (ORs) and 95%confidential interval (CI) were calculated by logistic regression analysis. Results: Compared with the commonTT genotype, the ERCC6 rs1917799 GG genotype was associated with increased GC risk (adjusted OR=1.46,95%CI: 1.03-2.08, P=0.035). When compared with (GT+TT) genotypes, the GG genotype also demonstrateda statistical association with increased GC risk (adjusted OR=1.38, 95%CI: 1.01-1.89, P=0.044). This was alsoobserved for the male subpopulation (GG vs. TT: adjusted OR=1.71, 95%CI: 1.12-2.62, P=0.013; G allele vs.T allele: adjusted OR=1.32, 95%CI: 1.07-1.62, P=0.009). Genetic effects on increased GC risk tended to beenhanced by H. pylori infection, smoking and drinking, but their interaction effects on GC risk did not reachstatistical significance. Conclusions: ERCC6 rs1917799 GG genotype might be associated with increased GCrisk in Chinese, especially in males.     

Association of a Pre-miR-27a Polymorphism with Cancer Risk: an Updated Meta-analysis

MicroRNA-27a is highly expressed in cancers and has been identified as an oncogenic microRNA. A geneticvariant in pre-miR-27a (rs895819) with a transition of A to G has been demonstrated to be associated with cancerrisk; however, the results of these studies remain conflicting rather than conclusive. Therefore, we performed ameta-analysis to derive a more precise estimation. Through searching PubMed or other databases up to March2014 using the following MeSH terms and keywords, “miR-27a”, “polymorphism” and “cancer”, seventeencase-control studies were identified in this meta-analysis, including 7,813 cases and 9,602. Crude odds ratios(ORs) and corresponding 95% confidence intervals (CIs) were calculated to investigate the association strengthbetween rs895819 and the susceptibility of cancer. The results of the overall meta-analysis did not suggest anyassociation between rs895819 polymorphism and cancer susceptibility, and this remained in Asians as a subgroup.In Caucasians, however, the rs895819 was associated with a reduced cancer risk in heterozygous (OR,0.83; 95%CI, 0.75-0.93) and dominant models (OR, 0.84; 95%CI, 0.76-0.93), and the [G] allele of rs895819showed a protective effect (OR, 0.90, 95%CI, 0.84-0.97). Further studies showed a significant association betweenthe [G] allele of rs895819 and decreased risk of breast cancer (0.91; 95%CI, 0.85-0.98), and stratified analysesindicated a protective effect of the [G] allele in Caucasians (OR, 0.89; 95%CI, 0.82-0.98), younger breast cancercases (OR, 0.87; 95%CI, 0.79-0.96), and in the group of unilateral breast cancer patients (OR, 0.90; 95%CI,0.83-0.97). These findings suggest an association between pre-miR-27a polymorphism rs895819 and cancer riskin Caucasians. The protective effect of rs895819 [G] allele in younger breast cancer and in the group of unilateralbreast cancer patients await further confirmation since the included studies in this meta-analysis were limited.     

The MDM2 SNP309T>G Polymorphism Increases Bladder Cancer Risk among Caucasians: a Meta-analysis

Published studies have evaluated associations between the MDM2 SNP309T>G polymorphism and bladder cancer susceptibility. However, these generated inconsistent results. The aim of the present investigation was to quantify the strength of association between MDM2 SNP309T>G polymorphism and bladder cancer risk by conducting a meta-analysis. We searched PubMed and Embase for related studies that had been published in English before April 1, 2014 and associations were assessed by summarizing the odds ratios (ORs) with thecorresponding 95% confidence intervals (CIs). Five case-control studies with a total of 972 cases and 1,012 controls were finally identified to be eligible for the meta-analysis. Overall, the results indicated that there was no significant association between the MDM2 SNP309T>G polymorphism and bladder cancer risk (for the allele model G vs. T: OR=1.08, 95% CI 0.85-1.36, p=0.54; for the co-dominant model GG vs. TT: OR=1.20, 95% CI 0.74-1.93, p=0.46; for the dominant model GG+GT vs. TT: OR=0.98, 95% CI 0.80-1.20, p=0.83; for the recessive model GG vs. GT+TT: OR=1.20, 95% CI 0.83-1.74, p=0.33). However, on subgroup analysis by ethnicity, significant associations were found in Caucasians in three models (for the allele model G vs. T: OR=1.41, 95% CI 1.10-1.81, p=0.006; for the co-dominant model GG vs. TT: OR=2.16, 95% CI 1.28-3.63, p=0.004; for therecessive model GG vs. GT+TT: OR=2.06, 95% CI 1.31-3.22, p=0.002). In summary, the present meta-analysis provides evidence that the genotype for the MDM2 SNP309T>G polymorphism may be associated with genetic susceptibility to bladder cancer among Caucasians.     

Meta-analysis of Associations between the MDM2-T309G Polymorphism and Prostate Cancer Risk

The mouse double minute 2 (MDM2) gene plays a key role in the p53 pathway, and the SNP 309T/G singlenucleotidepolymorphism in the promoter region of MDM2 has been shown to be associated with increased riskof cancer. However, no consistent results were found concerning the relationships between the polymorphismand prostate cancer risk. This meta-analysis, covering 4 independent case-control studies, was conducted tobetter understand the association between MDM2-SNP T309G and prostate cancer risk focusing on overall andsubgroup aspects. The analysis revealed, no matter what kind of genetic model was used, no significant associationbetween MDM2-SNP T309G and prostate cancer risk in overall analysis (GT/TT: OR = 0.84, 95%CI = 0.60-1.19;GG/TT: OR = 0.69, 95%CI = 0.43-1.11; dominant model: OR = 0.81, 95%CI= 0.58-1.13; recessive model: OR =1.23, 95%CI = 0.95-1.59). In subgroup analysis, the polymorphism seemed more likely to be a protective factorin Europeans (GG/TT: OR = 0.52, 95%CI = 0.31-0.87; recessive model: OR = 0.58, 95%CI = 0.36-0.95) thanin Asian populations, and a protective effect of the polymorphism was also seen in hospital-based studies in allmodels (GT/TT: OR = 0.74, 95%CI = 0.57-0.97; GG/TT: OR = 0.55, 95%CI = 0.38-0.79; dominant model: OR= 0.69, 95%CI = 0.54-0.89; recessive model: OR = 0.70, 95%CI = 0.51-0.97). However, more primary studieswith a larger number of samples are required to confirm our findings.     

Association Between p53 codon 72 Polymorphism and Cervical Cancer Risk Among Asians: a Huge Review and Meta-analysis

Objective: The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to derive amore precise estimation of the association between p53 codon 72 polymorphism (Arg72Pro, rs1042522 G>C) andcervical cancer risk among Asians. Methods: A literature search of Pubmed, Embase, Web of Science and CBMdatabases from inception through June 2012 was conducted. The meta-analysis was performed using STATA12.0 software. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength ofany association. Twenty-eight case-control studies were included with a total of 3,580 cervical cancer cases and3,827 healthy controls. When all the eligible studies were pooled into the meta-analysis, the results showed thatthe Pro/Pro genotype was associated with increased risk of cervical cancer under the heterozygous model (Pro/Pro vs. Arg/Pro: OR = 1.25, 95%CI: 1.02-1.53, P= 0.005). However, no statistically significant associations werefound under four other genetic models (Pro vs. Arg: OR = 0.97, 95%CI: 0.85-1.10, P= 0.624; Pro/Pro + Arg/Pro vs. Arg/Arg: OR = 0.84, 95%CI: 0.70-1.01, P= 0.058; Pro/Pro vs. Arg/Arg + Arg/Pro: OR = 1.13, 95%CI:0.92-1.39, P= 0.242; Pro/Pro vs. Arg/Arg: OR = 0.97, 95%CI: 0.76-1.22, P= 0.765; respectively). In the subgroupanalysis based on country, the Pro/Pro genotype and Pro carrier showed significant associations with increasedrisk of cervical cancer among Indian populations, but not among Chinese, Japanese and Korean populations.Conclusion: Results from the current meta-analysis suggests that p53 codon 72 polymorphism might be associatedwith increased risk of cervical cancer, especially among Indians.