Methylenetetrahydrofolate Reductase Polymorphisms and Susceptibility to Esophageal Cancer in Chinese Populations:a Meta-analysis

Although many epidemiologic studies investigated the methylenetetrahydrofolate reductase (MTHFR)polymorphisms and their associations with esophageal cancer, definite conclusions could not be drawn. To clarifythe effects of MTHFR polymorphisms on the risk of esophageal cancer, a meta-analysis was here performed inChinese populations. A total of 16 studies including 3,040 cases and 4,127 controls were involved in this metaanalysis.Overall, significant associations were found between the MTHFR C677T polymorphism and esophagealcancer risk when all studies in Chinese populations were pooled into the meta-analysis (T vs. C, OR = 1.19, 95%CI = 1.06–1.34; TT vs. CC, OR = 1.35, 95% CI = 1.07–1.70; TT+ CT vs. CC, OR = 1.29, 95% CI = 1.08–1.54;TT vs. CC + CT, OR = 1.19, 95% CI = 1.03–1.37). In subgroup analyses stratified by ethnicity and source ofcontrols, the same results were found in Kazakh (TT vs. CC, OR = 1.38, 95% CI = 1.02-1.87; TT + CT vs. CC,OR = 1.50, 95% CI = 1.03-2.18), in not stated populations (T vs. C, OR = 1.24, 95% CI = 1.08-1.42; TT vs. CC,OR = 1.47, 95% CI = 1.10-1.96; TT + CT vs. CC, OR = 1.30, 95% CI = 1.05-1.60; TT vs. CC + CT, OR = 1.32,95% CI = 1.12-1.56), and in hospital-based studies (T vs. C, OR = 1.34, 95% CI = 1.19-1.51; TT vs. CC, OR =1.81, 95% CI = 1.37-2.39; TT + CT vs. CC, OR = 1.51, 95% CI = 1.26-1.83; and TT vs. CC + CT, OR = 1.39,95% CI = 1.13-1.70). In conclusion, this meta-analysis provides evidence that the MTHFR C677T polymorphismcontributes to esophageal cancer development in Chinese populations.     

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.     

No Association of the TGF-β1 29T/C Polymorphism with Breast Cancer Risk in Caucasian and Asian Populations: Evidence from a Meta-Analysis Involving 55, 841 Subjects

The transforming growth factor-β1 (TGF-β1) gene 29 T/C polymorphism is thought to be associated withbreast cancer risk. However, reports are largely conflicting and underpowered. We therefore conducted a metaanalysisof all available case-control studies relating the TGF-β1 29T/C polymorphism to the risk of developingbreast cancer by including a total of 31 articles involving 24,021 cases and 31,820 controls. Pooled ORs weregenerated for the allele contrasts, with additive genetic, dominant genetic and recessive genetic models. Subgroupanalysis was also performed by ethnicity for the TGF-β1 29T/C polymorphism. No association was found in theoverall analysis (C vs T: OR=1.028, 95% CI=0.949-1.114, p-value 0.500; CC vs TC: OR= 1.022, 95% CI=0.963-1.085, p-value 0.478; CC vs TT: OR= 1.054, 95% CI=0.898-1.236, p-value 0.522; CC vs TT+ TC: OR= 1.031, 95%CI=0.946-1.124, p-value 0.482; TT vs CC+TC: OR= 0.945, 95% CI=0.827-1.080, p-value 0.403). Similarly, in thesubgroup analysis by ethnicity, no association was found in Caucasian (C vs T: OR= 1.041, 95% CI=0.932-1.162,p-value 0.475; CC vs TC: OR= 1.031, 95% CI=0.951-1.118, p-value 0.464; CC vs TT: OR= 1.081, 95% CI=0.865-1.351, p-value 0.493; CC vs TT+TC: OR= 1.047, 95% CI=0.929-1.180, p-value 0.453; TT vs CC+TC: OR= 0.929,95% CI=0.775-1.114, p-value 0.429;) and Asian populations (C vs T: OR= 1.004, 95% CI=0.908-1.111, p-value0.931; CC vs TC: OR= 0.991, 95% CI=0.896-1.097, p-value 0.865; CC vs TT: OR= 1.015, 95% CI=0.848-1.214,p-value 0.871; CC vs TT+TC: OR= 1.000, 95% CI=0.909-1.101, p-value 0.994; TT vs CC+TC: OR= 0.967, 95%CI=0.808-1.159, p-value 0.720;). No evidence of publication bias was detected during the analysis. No significantassociation with breast cancer risk was demonstrated overall or on subgroup (Caucasian and Asian) analysis.It can be concluded that TGF-β1 29T/C polymorphism does not play a role in breast cancer susceptibility inoverall or ethnicity-specific manner.     

Association of a common genetic variant in prostate stem-cell antigen with gastric cancer susceptibility in a Korean population

A recent genome wide association study (GWAS) indentified a significant association between rs2294008 (C > T) polymorphism in prostate stem-cell antigen (PSCA) and increased risk of gastric cancer in Japanese and Korean populations. The aim of this study was to determine whether rs2294008 polymorphism is associated with risk of gastric cancer in a Korean population. We conducted a large-scale case-control study of 3,245 gastric cancer patients and 1,700 controls. The frequencies of the CC, CT, and TT genotypes of rs2294008 polymorphism were 17.8%, 49.9%, and 32.3% in the gastric cancer patients; and 24.4%, 48.1%, and 27.5% in the controls, respectively. We found that the CT and TT genotypes were associated with a significantly increased risk of gastric cancer (OR(CT) = 1.50, 95% confidence intervals, 95% CI: 1.28-1.76; OR(TT) = 1.71, 95% CI: 1.43-2.04), compared with the CC genotype. Further, stratified by tumor location and histological type, the effect of the rs2294008 T allele was larger in cardia (OR(TT) = 2.62, 95% CI = 1.42-4.85) than non-cardia (OR(TT) = 1.67, 95% CI = 1.40-2.00), in diffuse-type (OR(TT) = 2.00, 95% CI: 1.55-2.59) than in intestinal-type (OR(TT) = 1.51, 95% CI: 1.22-1.86). Our study showed that rs2294008 in the PSCA gene was associated with increased risks of gastric cancer in a Korean population, suggests that rs2294008 might play an important role in gastric carcinogenesis.     

Association of TGF-β1 -509C/T polymorphisms with breast cancer risk: evidence from an updated meta-analysis

Epidemiological studies have evaluated the association between transforming growth factor-β1 (TGF-β1) -509C/T polymorphisms and breast cancer risk. However, the results remain conflicting rather than conclusive. The aim of this study was to comprehensively clarify the association between TGF-β1 -509C/T polymorphisms and breast cancer risk. All relevant studies were searched in the electronic databases. The potential sources of heterogeneity were detected with the chi-square-based Q test. The strength of associations between TGF-β1 -509C/T polymorphisms and breast cancer risk was measured by odds ratio (OR) and 95 % confidence intervals (CI). Publication bias was tested by Begg’s test and Egger’s test. A total of 10 studies including 10,913 cases and 14,187 controls were included in the meta-analysis. Overall, there was no evidence of significant association of TGF-β1 -509C/T polymorphisms with breast cancer risk (TT vs. CC [OR?=?0.97, 95 % CI?=?0.83–1.14]; CT vs. CC [OR?=?1.05, 95 % CI?=?0.90–1.22]; TT?+?CT vs. CC [OR?=?0.99, 95 % CI?=?0.91–1.08]; T allele vs. C allele [OR?=?0.99, 95 % CI?=?0.93–1.06]). Similar results were also found in the subgroup analyses by ethnicity and source of control. When stratified by estrogen receptor (ER) status, TT genotype and T allele were associated with a decreased ER-positive breast cancer risk (OR?=?0.66, 95 % CI?=?0.49–0.90 and OR?=?0.85, 95 % CI?=?0.75–0.96, respectively). The present meta-analysis results suggest that TGF-β1 -509C/T variants may not contribute to the risk of breast cancer overall. However, T allele may be a potential protective factor for developing ER-positive breast cancer. Well-designed studies with larger sample size were required to verify our findings further.     

IL-17 基因rs763780 位点的多态性与胃癌易感性的Meta分析

目的:用Meta 分析的方法评价IL-17 基因rs763780 位点的多态性与胃癌易感性的相关性。方法: 计算机检索PubMed、EMBASE、The Cochrane Library、Web of science、万方数据库、中国生物医学文献数据库、中文科技期刊数据库、中国期刊全文数据库,检索日期自各数据库开始建库至2017 年12 月,全面检索IL-17 基因rs763780 位点的多态性与胃癌易感性的病例对照研究文献,采用STATA 12.0 统计软件进行Meta 分析。结果: 最终纳入10 篇病例对照研究文献,共计3 892 例胃癌患者和4627 例健康对照。Meta 分析结果显示,IL-17 基因rs763780 位点多态性在等位基因模型(C vs T：OR=1.90, 95% CI=1.73～2.08)、相加模型(CC vs TT：OR=1.76, 95% CI=1.45～2.14)、共显性模型(CC vs CT：OR =1.26, 95% CI=1.13～1.42)、显性模型（CC vs CT+TT：OR=1.93, 95% CI=1.65～2.26）及与隐性模型（TT vs CT+CC：OR =1.67, 95% CI=1.38～2.03）下均与胃癌的易感性相关。结论：IL-17 基因rs763780位点多态性增加了胃癌的发病风险。     

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.     

CD44 rs13347 C>T polymorphism predicts breast cancer risk and prognosis in Chinese populations

ABSTRACT: INTRODUCTION: It has been demonstrated that the interplay of adhesion molecule CD44 and its ligands can regulate cancer cell proliferation, migration and invasion, as well as tumor-associated angiogenesis and is related to breast cancer patient survival. In this two-stage, case control study, we determined whether common functional tagSNPs (single nucleotide polymorphisms) are associated with breast cancer risk and prognosis. METHODS: Five tagSNPs of CD44 (rs10836347C>T, rs13347C>T, rs1425802A>G, rs11821102G>A, rs713330T>C) were selected and genotyped in 1,853 breast cancer patients and 1,992 healthy control subjects in Eastern and Southern populations. Potential function of rs13347C>T and association between this variation and breast cancer were further studied. RESULTS: Compared with the most common rs13347CC genotype, variant genotypes (CT and TT) increased an individual's susceptibility to breast cancer, especially in estrogen receptor (ER) negative patients (odds ratio (OR) = 1.37, 95%CI = 1.17 to 1.59 for ER positive patients; OR = 2.37, 95% CI = 2.00 to 2.80 for ER negative patients). We also found that rs13347CT+ TT genotypes predicts lower five-year survival rate (hazard ratio (HR) = 1.85, 95% CI = 1.09 to 3.15, P = 0.023), with the lowest survival probability in ER negative T allele carriers. Furthermore, our reporter assay findings, although preliminary and rather modest, showed that miR-509-3p may suppress CD44 expression more strongly in C allele carriers than T allele carriers (P < 0.01). Similarly, rs13347 variant genotypes (CT and TT) carriers were shown to have more CD44 expression than CC carriers in both immunohistochemistry (P < 0.001) and western blotting (P = 0.001) results. CONCLUSION: These findings suggest that CD44 rs13347C>T polymorphism may affect breast cancer development and prognosis by increasing CD44 expression.     

C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis

A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420Tpolymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a moreprecise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 availablestudies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significantassociation between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer,gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associatedwith decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838,95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysiswas performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverseassociation was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for thePB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association wasonly found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggestthat SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decreasecancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies willbe necessary to validate the risk identified in the current meta-analysis.     

Functional variants in the promoter of interleukin-1beta are associated with an increased risk of breast cancer: a case-control analysis in a Chinese population

Interleukin 1beta (IL-1beta) is a multifunctional cytokine that upregulates the inflammatory response, and participates in carcinogenesis, malignant transformation, tumor growth, invasion and metastasis. Two potentially functional polymorphisms (T-31C and C-511T) in the IL-1beta gene promoter were suggested to be correlated with alteration of IL-1beta expression and therefore may be associated with cancer risk. To test the hypothesis that these 2 polymorphisms are associated with risk of breast cancer, we performed a case-control study of 365 breast cancer cases, 270 patients with benign breast diseases (BBD) and 631 cancer-free controls in a Chinese population. Multivariate logistic regression analyses revealed that increased risk of breast cancer was associated with IL-1beta-31C variant genotypes [adjusted odds ratio (OR)=1.28 and 95% confidence interval (CI)=0.91-1.80 for -31CT and 1.72 (95% CI=1.16-2.54) for -31CC], compared with the -31TT genotype. Similarly, IL-1beta-511T variant genotypes were also associated with increased risk of breast cancer (adjusted OR=1.20, 95% CI=0.86-1.67 for -511CT and adjusted OR=1.74, 95% CI=1.18-2.56 for -511TT), compared with the -511CC genotype. Furthermore, cancer risks associated with IL-1betaT-31C variant genotypes were more evident in older women, postmenopausal women and individuals with a later menarche age. Interestingly, although we did not find significant associations of these 2 variants with cancer risk when compared with the BBD patients, a 1.27-fold (95% CI=1.01-1.60) increased risk was observed with the -31C-511T common haplotype. These findings indicate that these 2 IL-1beta promoter variants may contribute to risk of developing breast cancer in the Chinese population.     

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

Objective: The NAD(P)H:quinone oxidoreductase 1 (NQO1) rs1800566 polymorphism, leading to prolinetoserineamino-acid and enzyme activity changes, has been implicated in bladder cancer risk, but individuallypublished studies showed inconsistent results. We therefore here conducted a meta-analysis to summarize thepossible association. Methods: A systematic literature search up to August 27, 2012 was carried out in PubMed,EMBASE and Wanfang databases, and the references of retrieved articles were screened. Crude odds ratios (ORs)with 95% confidence intervals (CIs) were analyzed for homozygote contrast (TT vs. CC), additive model (T vs.C), dominant model (TT+CT vs. CC), and recessive model (TT vs. CC+CT) to assess the association using fixedorrandom-effect models. Results: We identified 12 case-control studies including 3,041 cases and 3,128 controlsfor the present meta-analysis. Significant association between NQO1 rs1800566 genetic polymorphism and riskof bladder cancer was observed in the additive model (OR = 1.15, 95% CI = 1.01-1.30, p = 0.030). Moreover, inthe subgroup analysis stratified by ethnicity, significant associations were observed in Asians (OR = 1.26, 95%CI = 1.08–1.47, p = 0.003 for T vs. C; OR = 1.68, 95% CI = 1.21-2.32, p = 0.002 for TT vs. CC; OR = 1.50, 95%CI = 1.13-1.98, p = 0.005 for TT vs. CT+CC) but not in Caucasians. Conclusions: The results suggest that NQO1rs1800566 genetic polymorphism may contribute to bladder cancer development, especially in Asians.     

Promoter polymorphism (-786t>C) in the endothelial nitric oxide synthase gene is associated with risk of sporadic breast cancer in non-Hispanic white women age younger than 55 years

BACKGROUND: Nitric oxide (NO) is constitutively synthesized in the endothelium by endothelial nitric oxide synthase (eNOS) and acts as a pleiotropic regulator involved in carcinogenesis. Most breast cancers develop from mammary epithelial cells; therefore, NO may play a role in their development. It was hypothesized that eNOS polymorphisms are associated with risk of breast cancer. METHODS: In the current hospital-based case-control study of 421 non-Hispanic white women with sporadic breast cancer and 423 frequency-matched control subjects, we genotyped 3 polymorphisms of eNOS (i.e., -786T>C, the 27-base pair [bp] variable number of tandem repeats [VNTR] in intron 4, and 894G>T [Glu298Asp]) and assessed their associations with risk of breast cancer. RESULTS: It was found that, compared with -786TT, the -786C variant genotypes were associated with a significantly increased risk of breast cancer in an allele dose-dependent manner (adjusted odds ratio [OR], 1.33 [95% confidence interval (95% CI)], 0.99-1.77 for -786TC; and OR, 1.79 [95% CI, 1.11-2.87] for -786CC; P(trend) = .007), but 27-bp VNTR and 894G>T genotypes were not. Stratification analysis demonstrated that the risk associated with -786C variant genotypes (-786TC/CC) was more pronounced in smokers and in those 50 years or older (OR, 1.82 [95% CI, 1.19-2.80] and OR, 2.08 [95% CI, 1.25-3.45], respectively), and in the estrogen and progesterone receptor-negative cases (OR, 1.70 [95% CI, 1.10-2.62] and OR, 1.57 [95% CI, 1.07-2.32], respectively). Furthermore, the C4G haplotype derived from the observed genotypes was also associated with a significantly increased risk of breast cancer (OR, 2.16; 95% CI, 1.07-4.36). CONCLUSIONS: The results suggest that eNOS polymorphisms (especially -786T>C) may play a role in the development of sporadic breast cancer.     

Quantitative assessment of the association between MTHFR C677T polymorphism and colorectal cancer risk in East Asians

A great number of studies regarding the association between MTHFR C677T polymorphism and risk of colorectal cancer (CRC) in East Asians were published, but the results were inconsistent. Thus, a meta-analysis was performed to investigate the association. PubMed, Embase, and CBM databases were searched for eligible publications. Pooled odds ratios (ORs) with 95?% confidence intervals (95?% CIs) were calculated using random or fixed effect models. Finally, 24 case?Ccontrol studies with a total of 7,230 CRC cases and 9,285 controls were included. Meta-analyses of a total of 24 studies showed there was a statistically significant association between MTHFR C677T polymorphism and decreased CRC risk in East Asians under four genetic models (T versus C, OR?=?0.92, 95?% CI 0.85?C0.99; TT versus CC, OR?=?0.80, 95?% CI 0.69?C0.94; TT versus CT/CC, OR?=?0.82, 95?% CI 0.71?C0.95; TT/CT versus CC, OR?=?0.92, 95?% CI 0.86?C0.98). The cumulative meta-analyses for the allele contrast (T versus C), homozygote (TT versus CC), dominant (TT/CT versus CC), and recessive (TT versus CT/CC) models all showed a trend of more obvious association as information accumulated by year. Subgroup analyses by country further identified this association in Korea and Japan. This meta-analysis suggests that MTHFR C677T polymorphism is associated with decreased risk of colorectal cancer in East Asians, and MTHFR 677T variant has a protective effect on colorectal cancer.     

VEGF 936C>T polymorphism and breast cancer risk: evidence from 5,729 cases and 5,868 controls

Vascular endothelial growth factor (VEGF) is one of the most potent endothelial cell mitogens and plays an important role in angiogenesis. Many published studies have evaluated the association between the VEGF 936C>T polymorphism and breast cancer risk. However, the published findings are inconsistent. In order to derive a more precise estimation of the association, a meta-analysis was performed in this study. A total of eight studies including 5,729 breast cancer cases and 5,868 controls were identified. Overall, no significant associations between the VEGF 936C>T polymorphism and breast cancer risk were found for TT versus CC (OR 0.93, 95% CI 0.73–1.19), CT versus CC (OR 0.91, 95% CI 0.77–1.09), TT/CT versus CC (OR 0.92, 95% CI 0.78–1.08), and TT versus CT/CC (OR 0.96, 95% CI 0.75–1.21). In the subgroup analysis by ethnicity, source of controls, and menopausal status, there was still no significant association detected in any of the genetic models. In summary, our results suggest that the VEGF 936C>T polymorphism may not contribute to breast cancer susceptibility.     

CASP8 polymorphisms, estrogen and progesterone receptor status, and breast cancer risk

OBJECTIVES: This study was conducted to evaluate the potential role of CASP8 genetic polymorphisms in the etiology of breast cancer in a case-control study, Korea. METHODS: Incident breast cancer cases confirmed histologically (n = 1,599) were recruited from two hospitals in Seoul during 2001-2005. Control subjects (n = 1,536) were selected from the Health Examinee Cohort from Seoul and Gyeonggi Province surrounding Seoul, Korea. Three SNPs (D302H D > H, 5'-UTR C > T, and K337K G > A) were genotyped by the primer extension assay. The CASP8 D302H, which was not polymorphic in 48 samples, was excluded in further genotyping. Odds ratios and 95% confidential intervals (95% CIs) were estimated by unconditional logistic regression model adjusted for age at enrollment, education, age at first full-term pregnancy, cigarette smoking, and family history of breast cancer. RESULTS: The 5'-UTR T allele containing genotypes (CT/TT) were associated with an increased risk of breast cancer, compared with those with the CC genotype (OR = 1.13, 95% CI = 0.95-1.34; and OR = 1.48, 95% CI = 1.04-2.10, respectively; P-trend = 0.02). When stratified by the estrogen and progesterone receptor status, the association between the 5'-UTR T allele and breast cancer risk was prominent in ER(+) and PR(+) cases among pre-menopausal women (OR = 1.31, 95% CI = 1.00-1.72 and OR = 1.40, 95% CI = 1.06-1.85, respectively), whereas the association was found prominent in ER(-) or PR(-) cases (OR = 1.32, 95% CI = 0.93-1.87 and OR = 1.42, 95% CI = 1.04-1.94, respectively) among post-menopausal women. CONCLUSION: Our results thus suggest that the CASP8 5'-UTR C > T are associated with breast cancer risks and the effect may be modified by estrogen and progesterone receptor status.     

Association of IL-10 rs1800871 and rs1800872 Polymorphisms with Breast Cancer Risk: A Systematic Review and Meta-Analysis

Background: The rs1800871 and rs1800872 polymorphisms of interleukin 10 (IL-10) gene has been indicated tobe associated with breast cancer (BC) risk, but study results are still debatable. To derive a more precise evaluation, weperformed a comprehensive meta-analysis. Methods: Multiple electronic databases were searched to identify studiesassessing the IL-10 rs1800871 and rs1800872 polymorphisms with BC risk. Results: A total of 21 case-control studieswith 6054 cases and 6355 controls were included in this met-analysis. There was a significant association between thers1800871 polymorphism and BC risk (CT vs. TT: OR= 1.17, 95% CI 1.01-1.35, p=0.02; and CC+CT vs. TT: OR= 1.29,95% CI 1.00-1.66, p=0.04). Moreover, increased BC risks were also associated with the rs1800872 polymorphism (Cvs. A: OR= 1.29, 95% CI 1.04-1.60, p=0.01; CC vs. AA: OR= 1.54, 95% CI 1.03-2.30, p=0.03; CC+CA vs. AA: OR=1.43, 95% CI 1.01-2.01, p=0.03; and CC vs. CA+AA: OR= 1.23, 95% CI 1.01-1.51, p=0.04). A pooling of the studieswas also conducted by ethnicity, but failed to show an association of IL-10 rs1800871 and rs1800872 polymorphismwith BC risk in Asians and Caucasians. Conclusions: Our results are inconsistent with previous meta-analysis suggeststhat IL-10 rs1800871 and rs1800872 polymorphisms might contribute to BC susceptibility in overall population, butnot by ethnicity.     

Association of polymorphisms in one-carbon metabolism genes and postmenopausal breast cancer incidence.

The interconversion of folates by the one-carbon metabolism pathway is essential for the synthesis of precursors used in DNA synthesis, repair, and methylation. Perturbations in this pathway can disrupt these processes and are hypothesized to facilitate carcinogenesis. We investigated associations of 25 candidate polymorphisms in nine one-carbon metabolism genes with risk of postmenopausal breast cancer using 502 cases and 505 controls from the Cancer Prevention II Nutrition Cohort. Four single nucleotide polymorphisms (SNP) in three different genes were significantly associated with breast cancer. The nonsynonymous R134K SNP in methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthase [MTHFD1; odds ratio (OR), 1.40; 95% confidence interval (95% CI), 1.06-1.85 for CT + TT] and an intronic SNP in formyltetrahydrofolate dehydrogenase (FTHFD; OR, 2.23; 95% CI, 1.09-4.54 for CC) were associated with a significant increase in risk. Significantly decreased risk was associated with an intronic SNP in FTHFD (OR, 0.75; 95% CI, 0.58-0.98 for CT + CC) and the A360A SNP in cystathionine beta-synthase (CBS; OR, 0.63; 95% CI, 0.41-0.96 for TT). The presence of at least one variant from both the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C SNPs was also associated with increased risk (OR, 2.16; 95% CI, 1.34-3.48 for 677 CT + TT/1,298 AC + CC). Investigations into interactions of the associated SNPs with each other and with dietary factors yielded inconclusive results. Our findings indicate that genetic variation in multiple one-carbon metabolism genes may influence risk of postmenopausal breast cancer and may involve changes in methyl donor synthesis. However, larger studies are needed to further examine gene/gene and gene/diet interactions in this pathway.     

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.     

Functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer

The FAS-FASL system plays crucial role in counterattack of cancer cell against immune system. This study examined the effects of FAS (-1377G/A and -670A/G) and FASL (-844T/C and 7896G/C) polymorphisms on breast cancer risk and apoptosis of T lymphocytes. The effect on breast cancer risk was determined by case-control analysis of 840 patients and 840 controls. The effects on T-lymphocyte apoptosis were determined by activation-induced cell death (AICD) of T cells ex vivo and by analyzing apoptotic tumor-infiltrating lymphocytes (TILs) in breast cancer tissue. We found moderately increased risk associated with FAS -1377AG [odds ratio (OR), 1.29; 95% confidence interval (CI), 1.05-1.59] and -1377AA (OR, 1.36; 95% CI, 1.01-1.82) genotypes compared with the -1377GG genotype and decreased risk associated with FASL -844CT (OR, 0.76; 95% CI, 0.62-0.94) and -844TT (OR, 0.66; 95% CI, 0.43-1.00) genotypes compared with the -844CC genotype. T lymphocytes with the FASL -844CC genotype had heightened FASL expression that is associated with increased AICD of the T cells stimulated by MCF-7 cells or phytohemagglutinin compared with the FASL -844TT genotype (10.38 +/- 4.09% and 24.29 +/- 1.50% versus 6.03 +/- 0.41% and 17.96 +/- 3.66%; P < 0.05 and 0.001). Breast cancer patients with the FASL -844CC genotype had higher apoptotic TILs in their cancer tissues than those with the FASL -844TT genotype (33.7 +/- 1.2% versus 19.1 +/- 2.0%; P = 0.007). These findings indicate that functional polymorphisms in FAS and FASL contribute to increased apoptosis of tumor infiltration lymphocytes and risk of breast cancer.     

5,10-Methylenetetrahydrofolate Reductase Polymorphisms and Colon Cancer Risk: a Meta-analysis

Previous studies investigating the association between 5,10-methylenetetrahydrofolate reductase (MTHFR)gene polymorphisms and colon cancer risk have generated conflicting results. The aim of our meta-analysis wasto clarify the precise association. A systematic literature search was conducted to identify all relevant studies.Pooled odds ratio (ORs) with 95% confidence interval (CI) were used to estimate the strength of the association.In this meta-analysis, a total of 13 articles, involving 5,386 cases and 8,017 controls met the inclusion criteria.Overall, a significant association was found between colon cancer risk and the MTHFR C667 polymorphism(TT vs CC+CT: OR=0.79; 95%CI=0.65-0.96; p=0.017). Stratification by ethnicity revealed that MTHFRC667was associated with colon cancer risk in the non-Asian group (TT vs CC+CT:OR=0.77, 95%CI=0.68-0.89,p=0.000; TT vs CC: OR=0.84, 95%CI=0.73-0.97, p=0.016). Stratification by source of control indicated thatMTHFR C667 also correlated with colon cancer risk in the population-based subgroup (TT vs CC: OR=0.85,95%CI=0.74-0.97, p=0.017; TT vs CC+CT: OR=0.78, 95%CI=0.68-0.89, p=0.000) and hospital-based subgroup(TT vs CC+CT: OR=0.65, 95%CI=0.49-0.86, p=0.003). However, risk was significantly increased for MTHFRA1298C polymorphisms and colon cancer risk in hospital-based studies (C vs A: OR=1.52, 95%CI=1.26-1.83,p=0.000; CC+AC vs AA: OR=1.93, 95%CI=1.47-2.49, p=0.000) but reduced in population-based studies (CCvs AA: OR=0.83, 95%CI=0.70-0.99, p=0.042). In conclusion, the results of our meta-analysis suggest that theMTHFR C667 polymorphism is associated with reduced colon cancer risk, especially for non-Asian populations.