E-钙黏蛋白基因3'-UTR+54C/T多态与肺癌的发病风险

目的 探讨CDHl基因3'-UTR+54C/T SNP与中国北方人群肺癌遗传易感性的关系.方法 采用聚合酶链反应一限制性片段长度多态性(PCR-RFLP)分析方法检测194名肺癌患者和223名健康对照组3'-UTR+54C/T SNP的基因型.结果 肺癌患者组吸烟个体比例明显高于对照组,吸烟可增加肺癌的发病风险(OR=3.03,95%CI=2.03～4.54).肺癌患者组C等位基因频率(85.6%)显著高于对照组(76.9%),两组相比差异有统计学意义(γ2=10.09,P=0.00);肺癌患者组与对照组T/T、T/C和C/C基因型频率分别为1.0%、26.8%、72.2%和4.0%、38.1%、57.8%,与T/T或T/C基因型相比,携带C/C基因型可显著增加肺癌的发病风险(OR=1.89,95%CI:1.25～2.85).结论 CDH1基因3'-UTR+54C/C基因型可能是中国北方人群肺癌发病的潜在危险因素.     

RASSF1基因单核苷酸多态性与食管癌的发病风险

目的:探讨RASSF1基因第三外显子G133T和第六外显子A315G单核苷酸多态性(SNP)与陕西地区汉族人群食管鳞状细胞癌(ESCC)易感性的关系.方法:采用基于人群的病例对照研究,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测120例ESCC和122例健康对照个体RASSF1基因多态位点的基因型频率分布,比较不同基因型与ESCC发生风险的关系.结果:RASSF1基因G133T多态的T等位基因频率和A315G多态的G等基因频率在ESCC患者组分别为17.5%和23.8%,显著高于健康对照组的6.1%和11.9%.根据个体吸烟状况进行分层分析发现,携带G/T基因型或T等位基因(G/T+T/T基因型)和携带A/G基因型或G等位基因(A/G+G/G基因型)可显著增加吸烟个体ESCC的发病风险,经性别、年龄、GIC家族史校正后的OR值分别为11.7和5.02(95%CI=3.95-34.9和2.09-12.06).GIC家族史分层分析发现,携带G/T基因型或T等位基因(G/T+T/T基因型)和A/G基因型可显著增加GIC家族史阳性个体和GIC家族史阴性个体ESCC的发病风险, 经性别、年龄、吸烟状况校正后的OR值为5.08和3.51(95%CI=1.85-13.92和1.69-7.21).结论:携带RASSF1基因G133T多态的T等位基因(G/T+T/T基因型)可能显著增加陕西地区人群ESCC的发病风险.携带RASSF1基因A315G多态的G等位基因(A/G+G/G基因型)可能显著增加陕西地区人群ESCC的发病风险.     

E2钙黏蛋白基因3′2 U TR + 54C/ T 多态与 肺癌的发病风险

 目的　探讨CDH1 基因3′2 U TR + 54C/ T SNP 与中国北方人群肺癌遗传易感性的关系。方法 采用聚合酶链反应2限制性片段长度多态性( PCR2RFL P) 分析方法检测194 名肺癌患者和223 名健康对 照组3′2 U TR + 54C/ T SNP 的基因型。结果　肺癌患者组吸烟个体比例明显高于对照组,吸烟可增加 肺癌的发病风险(OR = 3. 03 ,95 %CI = 2. 03～4. 54) 。肺癌患者组C 等位基因频率(85. 6 %) 显著高于对 照组(76. 9 %) ,两组相比差异有统计学意义(χ2 = 10. 09 , P = 0. 00) ;肺癌患者组与对照组T/ T、T/ C 和 C/ C 基因型频率分别为1. 0 %、26. 8 %、72. 2 %和4. 0 %、38. 1 %、57. 8 % ,与T/ T 或T/ C 基因型相比,携 带C/ C 基因型可显著增加肺癌的发病风险(OR = 1. 89 ,95 %CI = 1. 25～2. 85) 。结论　CDH1 基因3′2 U TR + 54C/ C 基因型可能是中国北方人群肺癌发病的潜在危险因素。     

RASSF1基因SNP与陕西地区结直肠癌发病风险关系的研究

目的:探讨RASSF1基因第三外显子G133T和第六外显子A315G单核苷酸多态性(SNP)与陕西地区汉族人群结直肠癌(CRC)易感性的关系。方法:采用基于人群的病例对照研究,聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测61例CRC和122例健康对照个体RASSF1基因多态位点的基因型频率分布,比较不同基因型与CRC发生风险的关系。结果:RASSF1基因G133T多态的T等位基因频率在CRC患者组为24.6%,显著高于健康对照组的6.1%(P=0.00)。与G/G基因型相比,携带G/T基因型的个体CRC的发病风险显著增加,经性别、年龄、吸烟状况、GIC家族史校正后的OR值为2.33(95%CI=1.05-5.15)。RASSF1基因A315G多态的G等位基因频率在CRC患者组为25.4%,显著高于健康对照组的11.9%(P=0.00)。根据个体吸烟状况进行分层分析发现,与A/A基因型相比,携带A/G基因型和G等位基因(A/G+G/G基因型)可显著增加吸烟个体CRC的发病风险,经性别、年龄、GIC家族史校正后的OR值为4.5(95%CI=1.65-12.28)。根据GIC家族史进行分层分析发现,与A/A基因型相比,携带A/G基因型或G等位基因(A/G+G/G基因型)可显著增加GIC家族史阳性个体CRC的发病风险,经性别、年龄、吸烟状况校正后的OR值为3.78(95%CI=1.39-10.19)。结论:携带RASSF1基因G133T多态的T等位基因(G/T+T/T基因型)可能显著增加陕西地区人群CRC的发病风险。携带RASSF1基因A315G多态的G等位基因(A/G+G/G基因型)可能显著增加陕西地区人群CRC的发病风险。分层分析发现,G等位基因(A/G+G/G基因型)可能显著增加吸烟个体和GIC家族史阳性个体CRC的发病风险。     

MMP-2基因启动子区单核苷酸多态性与高发区食管癌易感性的关系

目的:采用病例-对照研究,探讨基质金属蛋白酶-2(matrix metalloproteinase-2,MMP-2)启动子区C-1306T和C-735T单核苷酸多态性(single nucleotide polymorphisms,SNP)与河北省食管癌高发区-磁县食管鳞状细胞癌(esophageal squamous cell carcinoma,ESCC)遗传易感性的关系.方法:采用聚合酶链反应-限制性片段长度多态性(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)技术检测335例ESCC患者和624名健康对照的MMP-2 C-1306T和C-735T SNP的基因型频率分布.结果:MMP-2基因启动子区C-1306T多态的基因型及等位基因频率分布在ESCC患者组与对照组之间差异有统计学意义(Pgenotype=0.01和Pallele=0.02),与C/T+T/T基因型相比,C/C基因型显著增加ESCC的发病风险(OR=1.57,95%CI=1.10～2.23);以家族史和吸烟状况分层分析显示,C/C基因型可显著增加家族史阳性和吸烟个体的发病风险(OR=2.06和1.96,95%CI=1.19～3.55和1.09～3.53).C-735T多态的基因型及等位基因频率分布在ESCC患者组与对照组之间差异无统计学意义(P>0.05).结论:MMP-2基因启动子区C-1306T多态的C/C基因型可能是河北省磁县ESCC发病的危险因素,尤其可以增加家族史阳性及吸烟人群的发病风险;而C-735T SNP可能与食管癌发病风险无关.     

凋亡相关基因FAS及其配体FASL基因多态性与贲门癌发病风险相关性研究

目的:探讨FAS基因-1377G/A、-670A/G和FASL基因-844T/C单核苷酸多态(SNP)与贲门腺癌(GCA)遗传易感性的关系.方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测244例GCA患者和244名健康对照的FAS基因-1377G/A、-670A/G和FASL基因-844T/C SNP的基因型.结果:对照组FAS基因-1377G/A、-670A/G和FASL基因-844T/C SNP基因型分布符合Hardy-Weinberg平衡(P>0.05).FAS基因-1377G/A和-670A/G SNP可能与GCA的发病风险无关.GCA患者组FASL基因-844T/C SNP T等位基因频率为26.4%,明显高于对照组的20.5%(χ2=4.80,P=0.03),但两组的基因型频率分布差异无统计学意义(P>0.05).与FASL基因-844C/C基因型相比,携带C/T或T/T基因型显著增加贲门癌的发病风险(经性别、年龄和吸烟状况校正的OR=1.53,95%CI=1.06~2.21).FAS基因-1377G/A、-670A/G SNP的单体型分布在GCA患者组和对照组之间差异无统计学意义(P>0.05).结论:FASL基因-844T/C SNP T等位基因型可能是GCA发病的潜在危险因素;而FAS基因-1377G/A、-670A/G SNP与GCA遗传易感性无明显相关.     

β1-509C/T基因多态性与中国人群NSCLC遗传易感相关性的研究

目的:探讨转化生长因子β1基因(TGF-β1)-509C/T位点多态性与中国人群非小细胞肺癌(non-small cell lungcancer,NSCLC)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性PCR-RFLP方法检测210例NSCLC患者和208例健康对照者的TGF-β1-509C/T基因型分布,并分析两组之间的差异。结果:TGF-β1-509CT+TT基因型相对于CC基因型是NSCLC发生的独立危险因素(P=0.007,OR=2.297,95%CI:1.250～4.219);携带T等位基因者患NSCLC的风险是携带C等位基因者的1.617倍(P=0.001,95%CI:1.210～2.161);重度吸烟者相对于不吸烟和轻度吸烟者是NSCLC发生的独立危险因素(P=0.021,OR=1.783,95%CI:1.089～2.918)。结论:TGF-β1-509C/T位点多态性在中国人群中与NSCLC遗传易感性相关,可作为NSCLC发病风险评估的筛选指标。     

p73和MDM2基因多态性与卵巢上皮性癌发病风险的相关性

目的:探讨p73和鼠双微基因2(murine double minute 2, MDM2)启动子区单核苷酸多态性(single nucleotide polymorphisms, SNPs)与卵巢上皮性癌发病风险的关系.方法:采用聚合酶链反应-限制性片段长度多态性方法检测257例卵巢上皮性癌患者和257例健康志愿者妇女(对照组)的p73 G4C14/A4T14、MDM2 309T/G和MDM2 Del1518+/-这3个SNPs位点的基因型频率分布情况.结果:p73 G4C14/A4T14多态的等位基因和基因型频率在卵巢癌组和对照组中的分布差异无统计学意义(P=0.55,P=0.20);病例组中MDM2 309T/G SNP的G等位基因频率(46.7%)明显低于对照组(54.7%),2组比较差异有统计学意义(P=0.01),2组间基因型频率差异也有统计学意义(P=0.046);与MDM2 309T/G SNP的T/T基因型相比,T/G+G/G基因型可明显降低卵巢上皮性癌的发病风险[比值比(odds ratio,OR)=0.65, 95%可信区间(confidence interval,CI):0.44～0.97].进一步的分层分析显示,G等位基因携带者主要降低内膜样癌、Ⅲ～Ⅳ期卵巢癌和50岁以上卵巢癌的发病风险(OR=0.53, 95%CI:0.31～0.90; OR=0.62,95%CI:0.40～0.97; OR=0.59,95%CI:0.38～0.92).MDM2 Del1518+/- SNP的基因型和等位基因频率在卵巢癌组和对照组中的分布差异无统计学意义;分层分析显示,携带MDM2 Del1518+/+基因型会增加黏液性卵巢癌和Ⅰ～Ⅱ期卵巢癌的发病风险 (OR=2.01, 95%CI:0.93～4.37; OR=1.64, 95%CI:0.99～2.72).似然比检验发现,p73 G4C14/A4T14和MDM2 309T/G SNPs之间有明显的交互作用(P=0.03).结论:MDM2基因启动子区309T/G多态的G等位基因可能是卵巢上皮性癌发病风险的一个保护因素,且可能与p73 G4C14/A4T14多态间存在交互作用.     

肿瘤转移抑制基因NME1多态性与河北地区非小细胞肺癌相关性研究

目的 肿瘤转移抑制基因NME1启动子区的多态位点rs16949649T＞C和rs2302254C＞T与多种恶性肿瘤的侵袭能力及预后相关,但其与非小细胞肺癌(non-small cell lung cancer,NSCLC)的研究报道较少见.本研究探讨NME1基因rs16949649和rs2302254多态性与河北地区NSCLC的相关性.方法 选取2005-10-01-2010-01-31河北医科大学第四医院胸外科手术治疗的190例NSCLC患者以及190名性别与年龄相匹配的同一地区健康对照作为研究对象.应用聚合酶链反应(polymerase chain reaction,PCR)-连接酶检测反应(ligase detection reaction,LDR)的方法进行rs16949649和rs2302254基因分型.应用x2检验比较基因型和等位基因频率在不同组间的分布;非条件Logistic回归模型计算相对风险度的比值比(odds ratio,OR)及95％可信区间(confidential interval,CI);应用SHEsis在线软件构建单倍型并计算单倍型的OR值.结果 对照组NME1基因的rs16949649 TT基因型和rs2302254 CC基因型所占比例分别为40.5％和68.9％,显著高于NSCLC组的27.9％和53.7％,P值分别为0.012和0.007.携带rs16949649 C等位基因的基因型(TC+CC)个体患NSCLC的风险是携带TT基因型个体的1.86倍(95％CI:1.20～2.88),携带rs2302254T等位基因的基因型(CT+TT)个体患NSCLC的风险是携带CC基因型个体的1.94倍(95％CI:1.27～2.96).单倍型分析显示,携带rs16949649 C/rs2302254 T单倍型可显著增加NSCLC的发病风险(OR=1.82,95％CI:1.28～2.58).rs16949649和rs2302254基因型与肿瘤的病理类型、原发瘤大小、TNM分期和肿瘤转移无关,均P＞0.05;但是随着肿瘤转移程度的加重,风险型基因型所占比例出现逐步增高的趋势.结论 NME1基因的rs16949649和rs2302254多态性与河北地区NSCLC的发病风险相关.携带rs16949649 C等位基因的基因型(TC+CC)和携带rs2302254 T等位基因的基因型(CT+TT)可分别增加NSCLC的发病风险;携带rs16949649 C/rs2302254 T单倍型亦可显著增加NSCLC的发病风险.     

XPC基因Ala499Val、Lys939Gln多态与食管癌、贲门癌发病风险的关联

背景与目的:XPC基因参与核苷酸切除修复,该基因存在单核苷酸多态性(SNP)位点,并可能通过SNP位点碱基的改变影响其修复能力及疾病易感性。本研究旨在探讨XPC基因第8外显子Ala499Val及第15外显子Lys939GlnSNP与河北省食管癌、贲门癌高发区—磁县和涉县人群食管鳞状细胞癌(esophagealsguamouscellcarcinoma,ESCC)和贲门腺癌(gastriccardiacadenocorcinoma,GCA)遗传易感性的关系。方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法检测327例ESCC患者、253例GCA患者和612名健康对照的XPC基因第8外显子Ala499Val及第15外显子Lys939GlnSNP的基因型。结果:ESCC患者组、GCA患者组上消化道肿瘤家族史阳性个体比例明显高于对照组,上消化道肿瘤家族史可增加ESCC、GCA的发病风险(经性别和年龄校正后的OR=1.76和1.77,95%CI=1.34～2.32和1.31～2.39)。ESCC患者组和对照组的XPC基因第8外显子C、T等位基因频率及C/C、C/T、T/T基因型分布差异均无显著性(P>0.05)。GCA患者组T等位基因频率(26.5%)显著低于对照组(32.5%),两组相比差异有显著性(χ2=6.12,P=0.01);与C/C基因型相比,携带C/T基因型可显著降低GCA的发病风险(OR=0.62,95%CI=0.45～0.84)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与C/C基因型相比,携带C/T基因型可显著降低吸烟个体和家族史阴性个体GCA的发病风险(OR均等于0.57,95%CI=0.36～0.91和0.37～0.88)。在ESCC、GCA患者组和对照组之间,XPC第15外显子A、C等位基因频率及A/A、A/C、C/C基因型分布差异均无显著性(P>0.05)。根据吸烟状况和上消化道肿瘤家族史进行分层分析发现,与A/A基因型相比,携带C/C基因型可显著增加非吸烟个体ESCC的发病风险(OR=2.05,95%CI=1.15～3.66)。单体型分析显示,A/T、A/C、C/T、C/C四种单体型,在ESCC患者组与对照组之间分布差异无显著性(P>0.05);在GCA患者组与对照组之间分布差异有显著性(P=0.02)。与A/T单体型相比,携带A/C、C/C单体型可显著增加GCA的发病风险(OR=1.35和1.46,95%CI=1.01～1.81和1.06～2.00)。结论:在河北省食管癌、贲门癌高发区—磁县和涉县人群中,携带XPC基因第8外显子C/T基因型可能明显降低GCA的发病风险;第15外显子Lys939GlnSNP可能与ESCC、GCA的发病风险无关,但分层分析发现携带第15外显子C/C基因型可能增加非吸烟个体ESCC的发病风险;携带A/C、C/C单体型可能增加GCA的发病风险。     

Vascular endothelial growth factor genotypes, haplotypes, gender, and the risk of non-small cell lung cancer.

PURPOSE: The vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving tumor growth and metastasis. Polymorphisms in the VEGF gene may regulate VEGF production. In this large case-control study, we investigated whether functional polymorphisms (-460C/T, +405C/G, +936C/T) in the VEGF gene are associated with the risk of non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: VEGF genotypes and haplotypes were determined in 1,900 Caucasian patients with NSCLC and 1,458 healthy controls. The results were analyzed using logistic regression models, adjusting for age, gender, smoking status, pack-years of smoking, and years since smoking cessation (for ex-smokers). The false-positive report probability was estimated for the observed odds ratios (OR). RESULTS: There were no overall associations between individual VEGF genotypes and the risk of NSCLC. Stratified analysis suggested that the combined +405CC+CG genotype was significantly associated with increased risk of lung adenocarcinoma in males (adjusted OR, 1.40; 95% confidence interval, 1.03-1.87). In haplotype analysis, haplotypes were globally associated with differences between cases and controls in males (P = 0.03). Specifically, the -460T/+405G/+936C haplotype was significantly (P = 0.02) associated with decreased risk of adenocarcinoma in males when compared with the most common CGC haplotype (adjusted OR, 0.76; 95% confidence interval, 0.50-0.98). None of the VEGF genotypes and haplotypes studied significantly influenced the susceptibility to NSCLC in females. CONCLUSIONS: Polymorphisms of -460C/T, +405C/G, and +936C/T in the VEGF gene do not play a major role in NSCLC risk. However, we could not exclude a minor role for the +405CC+CG genotypes and the 460T/+405G/+936C haplotype in lung adenocarcinogenesis in male Caucasians.     

Single nucleotide polymorphisms in breast cancer susceptibility gene 1 are associated with susceptibility to lung cancer

BRCA1 is a tumor suppressor that has been found to be involved DNA synthesis during cell replication. In a recent study, the single nucleotide polymorphism (SNP), rs799917, in BRCA1 was found to be associated with the development and progression of various types of tumor. In the present study, the association between rs799917 and susceptibility to lung cancer was evaluated in a Han Chinese population in the Liaoning Province of China. The BRCA1 rs799917 genotypes (C/C, C/T and T/T) were analyzed using TaqMan quantitative PCR in 682 patients with lung cancer and 694 healthy controls, and the results were analyzed using a Student''s t-test, a χ² test and logistic regression analysis. Individuals carrying the C/T or T/T genotype had a lower risk of lung cancer compared with those carrying the C/C genotype [odds ratio (OR), 0.741; P=0.021; and OR, 0.610; P=0.011, respectively). The C/T + T/T genotype group had an even lower risk (OR, 0.709; P=0.005) compared with that in the C/C genotype group. In the stratified analyses of non-smokers, individuals with the C/T or T/T genotype had a lower risk of developing lung cancer compared with that in those carrying the C/C genotype (OR, 0.681; P=0.013; and OR, 0.569; P=0.021, respectively). The stratified analyses of the BRCA1 rs799917 polymorphism based on pathological type, chemotherapy and radiotherapy, showed that in the squamous cell carcinoma, non-chemotherapy and non-radiotherapy subgroups, individuals with the T/T genotype had a lower risk of lung cancer compared with that in those carrying the C/C genotype (OR, 0.454; P=0.007; OR, 0.485; P=0.002; and OR, 0.599; P=0.020, respectively). In conclusion, the T allele of the rs799917 SNP in BRCA1 was associated with a lower risk of lung cancer in the ethnic Han Chinese population in Liaoning Province and may represent a protective factor against lung cancer.     

Vascular endothelial growth factor gene polymorphisms and risk of primary lung cancer.

Angiogenesis is an essential process in the development, growth, and metastasis of malignant tumors including lung cancer. DNA sequence variations in the vascular endothelial growth factor (VEGF) gene may lead to altered VEGF production and/or activity, thereby causing interindividual differences in the susceptibility to lung cancer via their actions on the pathways of tumor angiogenesis. To test this hypothesis, we investigated the potential association between three VEGF polymorphisms (-460T > C, +405C > G, and 936C > T)/haplotypes and the risk of lung cancer in a Korean population. VEGF genotypes were determined in 432 lung cancer patients and 432 healthy controls that were frequency matched for age and sex. VEGF haplotypes were predicted using Bayesian algorithm in the phase program. Compared with the combined +405 CC and CG genotype, the +405 GG genotype found associated with a significantly decreased risk of small cell carcinoma [SCC; adjusted odds ratio (OR), 0.36; 95% confidence interval (95% CI), 0.17-0.78]. The 936 CT genotype and the combined 936 CT and TT genotype were also associated with a significantly decreased risk of SCC compared with the 936 CC genotype (adjusted OR, 0.47; 95% CI, 0.26-0.85 and adjusted OR, 0.44; 95% CI, 0.24-0.80, respectively). Haplotype CGT was associated with a significantly decreased risk of SCC (adjusted OR, 0.39; 95% CI, 0.18-0.87), whereas haplotype TCC conferred a significantly increased risk of SCC (adjusted OR, 1.63; 95% CI, 1.14-2.33). None of the VEGF polymorphisms studied significantly influenced the susceptibility to lung cancer except SCC. However, haplotypes TCT and TGT were significantly associated with the risk of overall lung cancer, respectively (adjusted OR, 0.38; 95% CI, 0.25-0.60 and adjusted OR, 3.94; 95% CI, 2.00-7.76, respectively). These effects of haplotypes TCT and TGT on lung cancer risk were observed in three major histologic types of lung cancer. These results suggest that the VEGF gene may be contribute to an inherited predisposition to lung cancer.     

Genetic polymorphisms of VEGF, interactions with cigarette smoking exposure and esophageal adenocarcinoma risk

Vascular endothelial growth factor (VEGF) is a major regulator of angiogenesis in the process of tumor growth and metastasis in esophageal adenocarcinoma (EA). Polymorphisms in the VEGF gene have been associated with altered VEGF expression and plasma VEGF levels. We hypothesized that polymorphisms of VEGF may contribute to EA risk. Functional polymorphisms in the VEGF gene (-460C/T, +405C/G and +936C/T) were determined in 308 patients with EA and 546 healthy controls. Logistic regression analysis was employed to assess the associations between genotypes, haplotypes of VEGF and EA risk, adjusting for multiple confounding factors. Compared with the +936CC genotype, the combined +936CT+TT genotypes were significantly associated with increased risk of developing EA, with adjusted odds ratio (OR) = 1.49 [95% confidence interval (CI), 1.05-2.12; P = 0.027]. The -460CT+CC were associated with increased risk of EA in smokers (adjusted OR = 1.57; 95% CI, 1.07-2.30; P = 0.021), whereas the -460CT/CC were associated with decreased risk of EA (adjusted OR = 0.47; 95% CI, 0.25-0.91; P = 0.025) in non-smokers. Compared with non-smokers with the +460TT, smokers with the +460CT+CC had significantly higher risk of EA (adjusted OR = 3.32; 95% CI, 1.56-7.10; P = 0.002). No overall or interacting association with EA risk was found for the +405C/G polymorphism. Haplotype CGT (-460C/+405G/+936T) was significantly associated with higher risk of EA (adjusted OR = 1.70; 95% CI, 1.04-2.73; P = 0.034). These results suggested that cigarette smoking modifies the association between VEGF polymorphisms and EA risk among Caucasians.     

Genetic Effects of Vascular Endothelial Growth Factor A (VEGF-A) and Its Association with Disease Progression in Breast Cancer Population of Saudi Arabia

Aim: Previous studies have shown that vascular endothelial growth factor (VEGFA) gene variants were associated with breast cancer risk. The goal of the current study was to evaluate the genetic effects of the vascular endothelial growth factor (VEGF) on the risk of breast cancer and its association with disease progression. Methodology: This case control study was conducted on 110 Breast cancer cases and 110 gender matched healthy controls. Vascular endothelial growth factor A (VEGF-A) 1 (-460T>C) genotyping was performed using Amplification refractory mutation system PCR method. The vascular endothelial growth factor A (VEGF-A) (-460T>C) genotypes were collated with different clinicopathological features of breast cancer patients. Results: A significant difference was observed between the genotype distribution of VEGF-A (-460T>C) among breast cancer cases and gender matched healthy controls (p=0.006). The frequencies of all three genotypes CC,CT,TT reported in the breast cancer patients and sex matched healthy controls were  4.54%, 46.36% ,49.20%  and 7.27%, 64.54%, 28.18% respectively. The increased susceptibility to breast cancer disease was found to be associated with VEGF (-460T>C) CC vs TT variant in codominant inheritance model OR 2.78 (0.83-9.26) RR 1.68(1.01 to 2.81) P=0.04. A significant association was reported with VEGF (-460T>C) (CC+CT vs. TT) variant in recessive inheritance model, (OR=2.45 (95% CI= (1.40-4.29), P=0.003. Our findings indicated that VEGF (-460T>C) TT genotype is associated with an increased susceptibility to breast cancer disease. Our result indicates a potential dominant effect of VEGF (-460T>C) TT genotype on susceptibility to the breast cancer disease. Conclusion: VEGF (-460T>C) TT genotype significantly increased the risk of breast cancer. VEGF-A (-460T>C) genetic ariability was significantly associated with distant metastasis of the disease. It may be a useful as predisposing genetic marker for breast cancer .Further studies with larger sample sizes are necessary to confirm our findings.     

Gastric cancer risk predisposition and prognostic significance of vascular endothelial growth factor (VEGF) gene polymorphisms—A case–control study in an Omani population

Vascular endothelial growth factor (VEGF) plays a central role in angiogenesis, tumor growth, and metastasis. We investigated the associations between VEGF gene polymorphisms and gastric cancer (GC) risk predisposition and prognostic characteristics in an Omani population, an ethnic group which has not been studied previously. We analyzed three VEGF polymorphisms (+405 G/C, ?460 T/C, and +936 C/T) by the extraction of genomic DNA from peripheral blood of 130 GC patients and 130 control subjects followed by VEGF genotyping using polymerase chain reaction restriction fragment length polymorphism (PCR‐RFLP) analysis. There were no significant associations between the VEGF polymorphisms and GC risk. There were significant correlations between the +405 C/C genotype and both poor tumor differentiation (P = 0.007) and lymph node metastasis (P = 0.03) and between the ?460 T/T genotype and poor tumor differentiation (P = 0.03) with a statistical trend toward lymph node involvement (P = 0.05). VEGF gene polymorphisms had no significant effects on survival, but the VEGF +405 G/G genotype had a statistical trend toward lower survival rate with a hazard ratio of 1.6 [95% CI, 0.9–2.9] compared with the VEGF +405 CC/GC combined genotype (P = 0.049). Multivariate analysis showed that disease stage at diagnosis and the +405 G/G genotype were independent variables of adverse prognostic significance. There were no associations between the six common haplotypes identified and both GC risk predisposition and survival. The current study suggests that VEGF polymorphisms have no role in GC risk predisposition, but may have prognostic significance in GC patients. Mol. Carcinog. © 2009 Wiley‐Liss, Inc.     

Vascular endothelial growth factor gene polymorphisms associated with prognosis for patients with gastric cancer.

BACKGROUND: The present study analyzed vascular endothelial growth factor (VEGF) gene polymorphisms and their impact on the prognosis for patients with gastric cancer. PATIENTS AND METHODS: Five hundred and three consecutive patients with surgically resected gastric adenocarcinoma were enrolled in the present study. The genomic DNA was extracted from paraffin-embedded tissue and four VEGF (-460T > C, -116G > A, +405G > C, and +936C > T) gene polymorphisms were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. RESULTS: The survival analysis showed no association of three VEGF gene polymorphisms with the prognosis. For the +936C > T polymorphism, the T/T genotype, however, had a worse overall survival (OS) compared with the C/C genotype (P = 0.037). The -460 T/C or C/C genotype was a poor prognostic factor in patients with stage 0 or I gastric cancer (OS: hazard ratio (HR) = 3.96, disease-free survival (DFS): HR = 4.87). In the haplotype analysis, the CACC haplotype was associated with a significantly worse survival when compared with the TGGC haplotype (OS: HR = 1.72, DFS: HR = 1.73). CONCLUSIONS: VEGF gene polymorphisms were found to be an independent prognostic marker for patients with gastric cancer. Consequently, the analysis of VEGF gene polymorphisms can help identify patient subgroups at high risk of a poor disease outcome.     

Population-based case-control study of VEGF gene polymorphisms and breast cancer risk among Chinese women.

Vascular endothelial growth factor (VEGF) is a major angiogenic factor involved in a number of pathologic processes, including neovascularization, a crucial step in the development of solid malignancies. Using data and specimens collected in the Shanghai Breast Cancer Study, a population-based case-control study conducted in urban Shanghai, China from 1996 to 1998, we evaluated the association of VEGF gene polymorphisms with breast cancer risk. Included in this study were 1,093 cases and 1,184 age-matched controls who had completed an in-person interview and donated a blood sample to the study. Polymorphisms in the promoter region (T -460C), 5' untranslated region (C +405G), and 3'untranslated region (C936T) were genotyped using the Taqman allelic discrimination assay. No statistically significant case-control difference was found for the C +405G and T -460C polymorphisms. However, the C936T polymorphism was associated with a reduced risk of breast cancer. Compared with CC genotype carriers, women who had the TT genotype showed a decreased risk [odds ratio (OR), 0.65; 95% confidence interval (95% CI) 0.41-1.02], and the inverse association was restricted to premenopausal women (OR, 0.45; 95% CI, 0.25-0.79). Six common haplotypes were identified. Compared with the most common haplotype (-460T/405C/936C), the -460T/405G/936T haplotype was associated with a reduced risk of breast cancer (OR, 0.67; 95% CI, 0.43-1.04), particularly in premenopausal women (OR, 0.47; 95% CI, 0.27-0.81). Our study suggests that the VEGF C936T polymorphism might be a susceptibility factor for breast cancer among Chinese women.     

VEGF基因多态性与肺痛遗传危险因素的关系

Objective:We investigated the potential association between vascular endothelial growth factor (VEGF) poly-morphisms and the risk of lung cancer. Methods:In the case-control study, we used PCR-RFLP technique to determine two VEGF genotypes-2578C/A and 936C/T in 171 lung cancer patients and 172 healthy controls for conformation, and construct-ed haplotypes of the two gene sites by PHASE1.0 software. Unconditional logistic regression model was used to analyze the statistical association of genontypes or haplotypes in the two groups adjusted by gender and age. Results:Compared with at least one -2578A allele, individuals with-2578CC genotype found associated with a significantly decreased risk of lung can-cer [P=0.001;adjusted odds ratio (OR), 0.391;95% confidence interval (95% CI), 0.226-0.686]. Analyses stratified by gender showed that the combined -2578 CA and AA genotype were also associated with a significantly decreased risk of lung cancer. (P=0.016;OR 0.303;95% CI=0.153-0.601 and P=0.018;OR=0.547;95% CI=0.331-0.903, respectively). The distribu-tion of the two haplotypes (936C/-2578C and 936C/-2578A) were significantly different between case-and -control groups (P = 0.016, OR=0.317, 95% CI=0.124-0.809 and P=0.018, OR=0.547, 95% CI=0.331-0.903). Analyses categorized by tumor histology showed that Haplotype C-C was associated with a significantly decreased risk of adenocarcinoma compared with the reference haplotypes. (P=0.004;OR=0.237;95% CI=0.090-0.627). Conclusion:These results suggest that the VEGF polymorphisms may be a critical factor for the risk of lung cancer.