Survivin Promoter Polymorphism (-31 C/G): A Genetic Risk Factor for Oral Cancer

Background: The polymorphism of survivin gene at its promoter region is one of the risk factors for OSCC . Thispolymorphism involves substitution of G for C (9904341), and it is present at the cell cycle dependent elements andcell cycle homology region repressor binding motif of promoter. This study aimed to find the association betweensurvivin -31C/G polymorphism and prevalence of OSCC in a subset of Pakistani population. Methodology: Thiscase-control study was conducted on 47 cases with and 101 healthy individuals with no family history of cancer. We usedpolymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) protocols. Results: The mostcommon site of oral cancer in our research was the buccal mucosa followed by tongue and the least one was the labialmucosa. The histological tumor type of all 47 cases was squamous cell type. In our research, stage II had the highestprevalence, accounting for 34% of patients, while the prevalence of stage I was 31% in the case group. The prevalenceof stage III and IV was 25% and 8%, respectively. The numbers of moderately and poorly differentiated tumors wereequal. We found a significant association between the CC genotype of survivin and OSCC prevalence (OR was 9.395at 95% CI: 1.0202-86.5251, p-value= 0.04). The GG genotype also showed significant P value (OR: 0.4709 with 95%CI: 0.2323- 0.9546 at a P VALUE of 0.0367). while no significant P value was noted for CG genotype (OR: 1.4317 with95% CI: 0.7513 -2.8658, p- value= 0.31). Conclusion: Survivin -31G/C polymorphism was strongly associated withOSCC prevalence. The C allele was more common in case group as compared to healthy individuals living in Pakistan.     

Association between Epstein-Barr Virus Gene Polymorphism and Breast Cancer Risk among Egyptian Females

Background: Epstein-Barr virus (EBV) has been implicated in the development of breast cancer (BC) since 1995. It is classified into A/B genotypes, C/D subtypes, and F/f variants according to variations in its genome. Aim: To determine the distribution difference of EBV types between BC patients and healthy controls in Egypt and to detect the association between different EBV types and BC characteristics. Methods: Three hundred and sixty-two participants (142 BC patients and 220 controls) were enrolled in this study. All participants were screened for EBV infection by determination of viral-capsid-IgG antibodies in their sera. EBNA-1 gene was detected by PCR in tumor biopsies of seropositive patients and in peripheral blood mononuclear cells of controls. A/B genotyping of EBV was performed by nested-PCR targeting the EBNA-2 gene. C/D subtypes and F/f variants were identified by Restriction fragment length polymorphism at BamHI-I W1/I1 and BamHI-F regions of EBV genome, respectively. Results: Among 362 participants, 300(82.9%) were EBV-seropositive, including 120/142(84.5%) of the BC patients and 180/220(81.8 %) of the controls. EBNA-1 gene was positive in 54(45%) of seropositive BC patients and in 38(21.1%) of seropositive controls. There was a significant association of EBNA-1 gene with breast cancer (OR=3.05, 95%CI=1.84-5.07). Moreover, EBNA-1 gene positivity was significantly associated with the more aggressive tumors. Genotype-A and prototype-F were predominant among patients (90.4%, 100%, respectively) as well as among controls (91.7%, 100%, respectively) with no statistical significant association with BC risk.  However, subtype-D was significantly more frequent in patients (95.6%) than in controls (64.7%) and was significantly associated with a higher BC risk as compared to subtype-C (OR=11.7, 95%CI=2.4-57.08). Subtype-D was significantly associated with higher grades tumors (100% among grade III),  with progesteron receptor-negative tumors and with HER2-positive tumors (100% for each). The combined genotypes that significantly associated with BC risk were ADF (OR=4.9) and BDF (OR=5.5). Conclusions: Subtype-D of EBV could be the only EBV type implicated in BC development among Egyptian females and associated more with poor prognosis.     

Contribution of Macrophage Migration Inhibitory Factor -173G/C Gene Polymorphism to the Risk of Cancer in Chinese Population

Background: Macrophage migration inhibitory factor (MIF) -173G/C (rs755622) gene polymorphism hasbeen associated with cancer risk. Previous studies have revealed that MIF -173G/C gene polymorphism mayincrease cancer in the Chinese population, while results of individual published studies remain inconsistentand inconclusive.We performed this meta-analysis to derive a more precise estimation of the relationship.Materials and Methods: We conducted a search on PubMed, Embase, MEDLINE, Cochrane Library ,ChineseNational Knowledge Infrastructure (CNKI), Wanfang, Weipu on Dec 31, 2014.Odds ratio (OR) and 95%confidence interval (95% CI) were used to assess the association. A total of eight studies including 2,186 casesand 2,285 controls were involved in this meta-analysis. Results: The pooled results indicated the significantassociation between MIF −173G/C polymorphism and the risk of cancer for Chinese population (CC + CGvs GG: OR=1.14, 95%CI=1.02-127, pheterogeneity<0.01; P =0.023; CC vs CG+GG: OR=1.12, 95%CI=1.02-1.23, pheterogeneity< 001; P =0.017;CC vs GG: OR=1.18, 95%CI=1.04-1.33, pheterogeneity<001; P =0.008;CG vs GG:OR=1.03, 95%CI=0.91-1.15, pheterogeneity<001; P =0.656; C vs G:OR=1.24, 95%CI=1.14-1.25,pheterogeneity<001; P <001). Subgroup analysis showed that in patients with “solid tumors”, heterogeneitywas very large (OR=0.94,95%CI=0.83-1.06,pheterogeneity=0.044; p=0.297). Within “non-solid tumors”, theassociation became even stronger (OR=6.62, 95 % CI=4.32-10.14, pheterogeneity<0.001; p <0.001). Conclusions:This study suggested that MIF −173G/C gene polymorphism may increase increase cancer in the Chinesepopulation.Furthermore, more larger sample and representative population-based casees and well-matchedcontrols are needed to validate our results.     

The TP53 intron 6 G13964C Polymorphism and Risk of Thyroid and Breast Cancer Development in the Iranian Azeri Population

Background: TP53 mutations are the most common genetic alterations in human cancers. There are alsoseveral polymorphisms in both exons and introns of TP53 that may influence its anti-tumor functions and increasethe risk of cancer development. Associations of the TP53 intron 6 G13964C polymorphism with increased risk ofdevelopment of several cancers have been investigated in numerous studies, but the results were controversialand conflicting. In this study, we aimed to investigate the probable association of this polymorphism with riskof both thyroid and breast cancers among the Iranian-Azeri population. Materials and Methods: We performedtwo separate case control studies on associations of the intron 6 polymorphism with two different kinds ofcancer. In one case-control study, a total of 75 patients with thyroid carcinoma and 180 controls were analyzedand the other study included 170 patients with breast cancer and 135 healthy women. The intron 6 genotypewas determined by RFLP-PCR and the SPSS 16 program was applied for data analysis. Results: For thyroidcancer, the frequencies of GG genotype were 96.0% in patients and 93.3% in controls. The GC genotype had afrequency of 4.0 % in patients and 6.7% in controls. In the study on breast cancer, the frequency of GG and GCgenotypes in patients were 95.3% and 4.7%, respectively. In breast related control group, the frequency of GGgenotype was 93.3 % and the frequency of GC genotype was 6.7%. None of the cases and controls had the CCgenotype. Conclusions: There was no significant association between the TP53 intron 6 G13964C polymorphismand risk of development of both thyroid and breast cancer in Iranian-Azeri patients.     

Significance of Serum Survivin and -31G/C Gene Polymorphism in the Early Diagnosis of Breast Cancer in Egypt

Background

Breast cancer is one of the most relevant malignancies among women. Molecular abnormalities in promotor region of survivin gene may account for overexpression of survivin and increased breast cancer risk. This study aimed to explore the potential association between survivin promotor gene -31G/C single nucleotide polymorphism (rs9904341) and its serum level alteration on one hand, and the risk of breast cancer in Egyptian patients on the other hand. It also aimed to assess the usefulness of survivin as an early noninvasive diagnostic biomarker and in breast cancer staging.

AR基因外显子1的CAG重复多态性与乳腺癌发生的关系

目的探讨AR(雄激素受体)基因外显子1的CAG重复多态性与乳腺癌发生的关系。方法研究对象为50例乳腺癌患者和50例健康者,从外周血淋巴细胞中提取基因组DNA,对AR基因外显子1的编码序列进行PCR扩增,扩增产物进行DNA序列测定,计算CAG重复频率。Wilcoxon rank test比较病例组和对照组的[CAG]n分布,采用多因素log回归分析[CAG]n对乳腺癌发病风险的影响。结果病例组[CAG]n为15～26,对照组为16～26;两组重复频率分布有差异(P=0.015),[CAG]n≥24时乳腺癌发病风险为[CAG]n≤20的5.6倍(P=0.04,OR=5.6)。结论 AR基因外显子1的CAG重复频率对乳腺癌风险发病有影响,长[CAG]n可增大乳腺癌发病风险。     

Lack of any Association of the CTLA-4 +49 G/A Polymorphism with Breast Cancer Risk in a North Indian Population

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an important protein involved in the regulation of theimmune system. The +49 G/A polymorphism is the only genetic variation in the CTLA-4 gene that causes anamino acid change in the resulting protein. It is therefore the most extensively studied polymorphism among allCTLA-4 genetic variants and contributions to increasing the likelihood of developing cancer are well known invarious populations, especially Asians. However, there have hiterto been no data with respect to the effect of thispolymorphism on breast cancer susceptibility in our North Indian population. We therefore assayed genomicDNA of 250 breast cancer subjects and an equal number of age-, sex- and ethnicity-matched healthy controlsfor the CTLA-4 +49 G/A polymorphism but no significant differences in either the gene or allele frequency werefound. Thus the CTLA-4 +49 G/A polymorphism may be associated with breast cancer in other Asians, but itappears to have no such effect in North Indians. The study also highlights the importance of conducting geneticassociation studies in different ethnic populations.     

Association Between Survivin Gene Polymorphisms and the Susceptibility to Colon Cancer Development in the Turkish Population

Background: Colon cancer is one of the most common cancers worldwide. Apoptosis is a necessaryphysiological process for cell elimination which is very important both cellular homeostasis and cell proliferationand differantiation. Dysregulation can lead to uncontrolled cell growth and tumor development. Survivin, amember of the IAP family, plays a key role in promotion of cell proliferation as well as inhibition of apoptosis incancer cells. The aim of this study was to investigate whether specific genetic polymorphisms of survivin could beassociated with colon cancer development and progression in a Turkish population. Our study is the first to ourknowledge to investigate the relationship between colon cancer risk and survivin gene polymorphisms. Materialsand Methods: The relation between colon cancer and survivin -31 G/C (rs9904341), -241 C/T (rs17878467) and-625 C/G (rs8073069) polymorphism in promotor site of survivin gene associated with apoptosis was investigatedusing the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results:Individuals with -31C allele and CC genotype were found to have a higher risk of developing colon cancer(OR=13.4, p=0.01). The -241 CT genotype considerably increased the risk of colon cancer (OR=12.0, p=0.0001).However, there was no significant varaition of the survivin -625 C/G polymorphism among colon cancer patientsand controls in our study. Conclusions: This study provides the first evidence that survivin -31 G/C and -241C/T SNP significantly contribute to the risk of colon cancer in the Turkish population.     

Association between Microrna 146a and Microrna 196a2 Genes Polymorphism and Breast Cancer Risk in North Indian Women

Background: Micro RNAs (miRNAs) are small, noncoding RNA molecules. They can function as either oncogenes or tumor suppressor genes. Single nucleotide polymorphisms (SNP) present in the pre-miRNA region could affect the processing of miRNA and thus alter mature miRNA expression. The studies done so far had shown conflicting results regarding association of two common polymorphisms i.e.hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913 with breast cancer. OBJECTIVE: In the study, we examined the hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913 SNP association with breast cancer patients in north Indian women. Materials and Methods: This study included 100 breast cancer patients and 100 controls and was done over a period of two years. Genotypes of the hsa-miR-146 (rs2910164 G>C) and hsa-miR-196a2 (rs11614913 C>T) were identified by polymerase chain reaction – restriction length polymorphism (PCR-RFLP) technique in peripheral blood DNA samples. Statistical analysis: We assessed the strength of association of miRNA polymorphisms with breast cancer using Odds ratio (OR) along with 95% confidence intervals. Results: Heterozygous genotypes of hsa-miR-196a2 rs11614913 and combined hsa-miR-146 rs2910164 & hsa-miR-196a2 polymorphism were associated with significantly increased risk of breast cancer (OR-1.7, 95% CI–1.00-3.18) and (OR-1.9, 95% CI-0.85-4.46) respectively. Conclusion: Our study suggests that rs2910164 GC and rs11614913 CT genotypes may contribute to breast cancer susceptibility in north Indian women.     

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population

Background: Breast cancer is a leading cause of death in women worldwide. Genetic polymorphisms have beenreported to be important etiological factors. Murine double minute 2 (MDM2) T309G interacts with p53 and mutationsin p53 are present in approximately 50% of all cancers. However, it has been reported that effect of the polymorphismon breast cancer risk may vary in different populations. Here, we therefore investigated whether there is an associationbetween MDM2 T309G (rs2279744) polymorphism and breast cancer in a Turkish population. Materials and Methods:We analysed 110 patients with breast cancer and 138 matched? controls. For genotyping, polymerase chain reactionand restriction length fragment polymorphism methods were used. Results: A significant difference was observedbetween case and control groups with regard to the distribution of the MDM2 T309G polymorphism (p<0.05). Therewas a significantly higher frequency of the TT genotype in the control group (p=0.028; OR, 2.42; 95% CI, 1.09-5.37).However, we did not find any relationships among tumor grade and metastasis status and this polymorphism. Conclusion:This study indicates that the MDM2 T309G polymorphism GG genotype and the TG+GG combination may be riskfactors for breast cancer in our Turkish population.     

Vascular Endothelial Growth Factor (VEGF) Gene Polymorphisms and Breast Cancer Risk in a Chinese Population

Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis and thereby involved in thedevelopment and progression of solid tumours. Associations between three VEGF gene polymorphisms (-634G/C, +936 C/T, and +1612 G/A) and breast cancer risk have been extensively studied, but the currently availableresults are inconclusive. Our aim was to investigate associations between three VEGF gene polymorphisms andbreast cancer risk in Chinese Han patients. We performed a hospital-based case-control study including 680female incident breast cancer patients and 680 female age-matched healthy control subjects. Polymerase chainreaction restriction fragment length polymorphism (PCR-RFLP) analysis was performed to detect the threeVEGF gene polymorphisms. We observed that women carriers of +936 TT genotypes [odds ratio (OR) =0.46,95% confidence interval (CI) = 0.28, 0.76; P=0.002] or 936 T-allele (OR=0.81, 95% CI= 0.68, 0.98; P=0.03) hada protective effect concerning the disease. Our study suggested that the +1612G/A polymorphism was unlikelyto be associated with breast cancer risk. The -634CC genotype was significantly associated with high tumoraggressiveness [large tumor size (OR=2.63, 95% CI=1.15, 6.02; P=0.02) and high histologic grade (OR=1.47,95% CI= 1.06, 2.03; P=0.02)]. The genotypes were not related with other tumor characteristics such as regionalor distant metastasis, stage at diagnosis, or estrogen or progesterone receptor status. Our study revealed thatthe VEGF -634 G/C and +936 C/T gene polymorphisms may be associated with breast cancer in Chinese Hanpatients.     

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

Background: The 2518 A/G polymorphism in the MCP-1 gene has been extensively studied for associationswith cancer; however, results from replication studies have been inconsistent. The aim of this investigationwas to determine links with risk of cancer by meta-analysis. Methods: We searched Pubmed, Embase, CNKI,Weipu and Wanfang databases, covering all case-control studies until March, 2013. Statistical analyses wereperformed using the Revman 5.0 software. Results: A total of 11 case-control studies met our inclusion criteria,including 1,422 cases and 2,237 controls. The results indicated that the MCP-1 2518 gene polymorphism had noassociation with cancer risk overall (GG vs.GA+ AA: OR = 0.89, 95%CI = 0.61–1.28, P = 0.52). However, in thesubgroup analysis by ethnicity, a decrease of cancer risk was found in Asian populations (GG vs.GA+ AA: OR =0.79, 95%CI = 0.63–0.99, P = 0.04). Conclusion: This meta-analysis suggested that the 2518A/G polymorphismof MCP-1 gene is associated with risk of cancer among Asian, but not in Caucasian populations.     

IFN-γ基因+874位点单核苷酸多态性与乳腺癌的相关性

 目的探讨IFN-γ基因+874位点单核苷酸多态性与乳腺癌的相关性。方法采用PCR技术对94例乳腺癌患者及96例正常女性IFN-γ基因+874位点A/T单核苷酸多态性(SNP)进行分析,将PCR产物进行克隆、测序。结果乳腺癌患者IFN-γ基因+874位点TT基因型频率为18.1%,显著高于正常人的8.3%,两者之间比较具有显著性差异(χ²=3.95,P=0.047);乳腺癌病例组T等位基因频率显著高于对照组(χ²=4.984,P=0.026)。进一步分析显示,乳腺癌病例组中不同年龄段基因型频率和等位基因频率相比,均无显著性差异。结论IFN-γ基因+874位点TT基因型可能与乳腺癌的发生相关,T等位基因可能为乳腺癌发生的遗传危险因素。     

The G801A Polymorphism in the CXCL12 Gene and Risk of Breast Carcinoma: Evidence from a Meta-Analysis Including 2,931 Subjects

More and more evidence indicates that the G801A polymorphism in the CXCL12 gene might be associatedwith susceptibility to breast carcinoma in humans being. However, individually published results havebeen inconsistent. The purpose of this meta-analysis was to investigate the association between the G801Apolymorphism in the CXCL12 gene and breast carcinoma risk. A complete search strategy was done by theelectronic databases including PubMed and Chinese Biomedical Literature Database. A meta-analysis includingseven individual studies was carried out in order to explore the association between the G801A polymorphism inthe CXCL12 gene polymorphisms and breast carcinoma. The pooled odds ratios (ORs) and their corresponding95% confidence intervals (95%CIs) between the G801A polymorphism in the CXCL12 gene and breast carcinomarisk were assessed by the random-effects model. A significant relationship between the G801A polymorphism inthe CXCL12 gene and breast carcinoma was discovered in an allelic genetic model (OR: 1.214, 95%CI: 1.085-1.358, p=0.001), a homozygote model (OR: 1.663, 95%CI: 1.240-2.232, p=0.001), a heterozygote model (OR:1.392, 95%CI: 1.190-1.629, p=0.000), a recessive genetic model (OR: 1.407, 95%CI: 1.060-1.868, p=0.018) and adominant genetic model (OR: 1.427, 95%CI: 1.228-1.659, p=0.000). On sub-group analysis based on ethnicity,significance was observed between the European group and the mixed group. A significant relationship wasfound between the G801A polymorphism in the CXCL12 gene and breast carcinoma risk. Individuals with theA allele of the G801A polymorphism in the CXCL12 gene are under a higher risk for breast carcinoma.     

No Association of the 5'Promoter Region Polymorphism of CYP17 with Breast Cancer Risk in Japan

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5'promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5–50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58-1.64) for TC-genotype and 0.81 (0.39–1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother/sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5'promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.     

Association of Single Nucleotide Polymorphisms of the MDM4 Gene With the Susceptibility to Breast Cancer in a Southeast Iranian Population Sample

Introduction

The murine double minute 4 (MDM4) protein is a negative regulator of p53, and its upregulation has been observed in many tumor types. Previous literature suggested that genetic variations in the MDM4 gene are associated with risk of different cancers. The objective of the present study was to examine the effect of 3 common genetic variants of MDM4, rs4245739 A>C, rs11801299 G>A, and rs1380576 C>G, on the risk of breast cancer (BC) in a southeast Iranian population sample.

Glutathione S-transferase Gene Variants and Risk of BenignProstate Hyperplasia in a North Indian Population

Glutagthione S-transferase (GST) is over-expressed in benign prostate hyperplasia (BPH) patients, but thesignificance of GST polymorphisms for susceptibility to diseases of the prostate is unclear. The objectives ofthis study were to determine relationships between polymorphisms in the GSTM1, T1 and P1 genes with risk ofsymptomatic BPH and influence on standard therapy. A gene polymorphism association study conducted with 160symptomatic BPH patients with BPE (benign prostatic enlargement) and LUTS (lower urinary tract symptoms)and 200 age-matched controls. Patient inclusion criteria are age >50 years prostate size >30cm3, AUA (Americanurological association) score >7 and PVR volume ≤200 ml. Patients were treated with α-adrenergic blockersand 5α-reductase inhibitors for 6 months and subdivided based on their significant improvement in parametersbetween pre and post 6 month combined therapy to study associations with the GST polymorphisms. The GSTT1and GSTM1 variants genotyped with multiplex-PCR, whereas GSTP1 polymorphisms were determined withPCR-RFLP (polymerase chain reaction- restriction fragment length polymorphism). We observed a lack ofany association with the GSTT1 (p=0.45, OR=2.25, 95% CI=1.71-2.22) and GSTP1 (p=0.92 and 0.99) genes.However, there was a significant link with the null alleles of the GSTM1 (p=0.000, OR=2.24, 95%CI=1.46-3.42)gene. The combined analysis of the three genotypes demonstrated further increase in the risk of symptomaticBPH (p= 0.009, OR= 8.31 95%CI=1.71-40.37). Polymorphisms of GST genes were not associated with respondersor non-responders. Thus the GSTM1 deletion polymorphism is significantly associated with increased risk ofsymptomatic BPH, but none of the genes appearedto influence response to standard BPH therapy.     

KRAS Gene Polymorphisms and their Impact on Breast Cancer Risk in an Iranian Population

Single nucleotide polymorphisms (SNPs) in the let-7 miRNA binding site within the 3’ untranslated region (3’UTR) of KRAS appear related to the risk of cancer. The present case-control study was conducted with 244 BC patients and 204 healthy women to examine whether KRAS polymorphisms (rs61764370 T/G and rs712 G/T) are associated with breast cancer (BC) risk in an Iranian population. The polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method was used for genotyping of KRAS SNPs. Our results showed that the rs61764370 TG genotype (OR= 3.73; 95% CI =1.38-10.08; P=0.007) as well as the G allele OR= 3.56; 95% CI =1.33-9.53; P=0.008, respectively) increased the risk of BC. However, the KRAS rs712 TT vs GG+GT genotype in a recessive model was associated with a reduced risk of BC (OR= 0.56; 95% CI =0.38-0.84; P=0.006). In addition, the rs712 T allele decreased the risk of BC compared with the G allele (OR=0.75, 95%CI=0.58-0.97, P=0.031). However, we found no relationship among KRAS SNPs and clinicopathological characteristics of BC patients (P>0.05). Taken together, the present study provided evidence of relationships between KRAS polymorphisms and BC risk in a southeast Iranian population. Additional studies using larger sample sizes and diverse ethnicities are now warranted.     

The Methylenetetrahydrofolate Reductase C677T Polymorphism and Breast Cancer Risk in Asian Populations

Background: Methylenetetrahydrofolate (MTHFR) is the key enzyme of the folate metabolic pathway andseveral studies have pointed to association between the MTHFR C677T polymorphism and breast cancer risk.Although significant association was observed in some studies, in others no clear link could be established.Objective: A meta-analysis of published Asian case control studies was therefor carried out to shed further lighton any C677T breast cancer association. Materials and Methods: PubMed, Springer Link, Google Scholar andElsevier databases were searched for case control studies of associations between MTHFR C677T polymorphismand breast cancer risk. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess theassociation. A total of 36 studies including 8,040 cases and 10,008 controls were included in the present metaanalysis.Results: Overall, a significantly elevated breast cancer risk was associated with the T allele and TTgenotype in homozygote comparison and dominant genetic models when all studies were pooled into the metaanalysis(T vs C (allele contrast model): OR=1,23, 95%CI=1.13-1.37, p=0.000 ; TT vs CC(homozygote model):OR=1.38, 95%CI=1.16-1.63, p=0.0003; TT+CT vs CC (dominant model): OR=1.12, 95%CI=1.01-1.23, p=0.02).Conclusions: The present meta-analysis strongly suggested a significant association between the MTHFR C677Tpolymorphism and risk of breast cancer in Asian populations.